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train · 702k rows

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__label__wiki	0.529893	0.529893	Central banks snap up new ADB USD bond issue The 3-year bond, with a coupon rate of 1.875% per annum payable semi-annually and a maturity date of 19 July 2022, was priced at 99.898% The transaction was lead-managed by Bank of America Merrill Lynch, BNP Paribas, Citi, and TD Securities 59% of the bonds were placed in Asia; 24% in the Americas; and 17% in Europe, the Middle East, and Africa MANILA, Philippines - The Asian Development Bank (ADB) on Wednesday returned to the U.S. dollar bond market with the pricing of a $3.25 billion 3-year global benchmark bond issue, proceeds of which will be part of ADB's ordinary capital resources. "The breadth and depth of investor sponsorship enjoyed by ADB was demonstrated by the achievement of a sizeable order book. This high level of support which enabled ADB to tighten the price guidance against a volatile market backdrop highlights the high regard for ADB's credit and development mandate," ADB Treasurer Pierre Van Peteghem said Wednesday. The 3-year bond, with a coupon rate of 1.875% per annum payable semi-annually and a maturity date of 19 July 2022, was priced at 99.898% to yield 7.75 basis points over the 1.75% U.S. Treasury notes due June 2022. The transaction was lead-managed by Bank of America Merrill Lynch, BNP Paribas, Citi, and TD Securities. A syndicate group was also formed consisting of Commerzbank, DBS, Deutsche Bank, DNB Bank, and Nordea Bank. With more than 75 investors taking part, the issue achieved wide primary market distribution with 59% of the bonds placed in Asia; 24% in the Americas; and 17% in Europe, the Middle East, and Africa. By investor type, 71% of the bonds went to central banks and official institutions, 21% to banks, and 8% to fund managers and other types of investors. ADB says it plans to raise around $21 billion from the capital markets in 2019.	cc/2019-30/en_head_0044.json.gz/line3279
__label__wiki	0.831741	0.831741	Sharks Store HARVEY NORMAN WOMEN'S PREMIERSHIP Tahina Booth making her mark at the Sharks Mary Konstantopoulos NRL.com Reporter Wed 15 May 2019, 12:34 PM For Tahina Booth, having the opportunity to play for the Cronulla Sharks in this year’s Harvey Norman Women’s Premiership has been a game-changer. Tahina only recently returned to the game after some time away and is enjoying playing alongside some of the biggest names in women’s rugby league. "When Ruan Sims speaks, I am just in awe. I am a low-key fan girl. I feel the same way about Corban McGregor. I love the team and I love the culture," she said. Whilst Tahina may be in awe of her team-mates, she hasn’t had the opportunity to share her personal story with them. Undoubtedly, if the rest of the team knew that story, they would be low-key fan-girling about her, too. Tahina grew up in Papua New Guinea and has a deep personal understanding about the levels of gender inequality that exist there. She was raped at age seven by a person known to her family. She was told that if she told anyone what had happened, they would kill her family. The Jillaroos and Orchids after their clash in PNG in 2018. ©Nathan Hopkins/NRL Photos Out of love for her family and fear of the consequences, Tahina kept this a secret until she was 18. It was then that she began to comprehend that the depression and anxiety she was experiencing was a result of that trauma suffered as a child. From that moment, Tahina could begin to get the healing she needed, and sport played a huge role. "As the years went by, I used sport and the power of sport to take control of my body, to find my voice and to say that I matter," Tahina said. "What those people did to me is not going to break my spirit. I am where I am today because of sport." As a teenager, Tahina participated in athletics, basketball, tennis, surfboat rowing, gridiron and rugby league. But it was when she was competing for Papua New Guinea in powerlifting at the South Pacific Games that Tahina realised she could have an even greater impact. "On the day of competition, out of the 50 athletes competing, I was the only one with all the correct gear, because I was sponsored," she said. "There were all these incredible athletes getting disqualified because they were sharing uniforms and gear and consequently being timed out because they weren’t changing fast enough. "So I went back to Australia and asked my social media following if they had any gear to give, because I could hand it directly to the athletes. The post went viral. I thought I would have to organise excess baggage, instead I had to order a shipping container." The Grass Skirts Project was born and has now grown into an organisation that looks to help create the cultural and societal change in Papua New Guinea necessary to improve the status and health of women through sport. One of the most successful programs run by GSP was the Hevea Cup Carnival and Wellness Expo which was launched on International Women’s Day in Port Moresby. Tahina Booth in full cry against the Jillaroos. ©Nathan Hopkins/NRL Photos The idea was to connect people in PNG with specialist Non-Governmental Organisations that promote health and well-being. A total of 24 teams competed - 12 men’s teams and 12 women’s teams - while 20 NGOs were also invited to host stalls. When Tahina arrived at 6.30am to begin setting up, there was a group of 200 women waiting to enter. They were all waiting to hear from Marie Stopes about cervical cancer screenings. "In Papua New Guinea we need to be engaging more with sporting events to deliver health initiatives," Tahina said. "My goal is for the Hevea Cup to be rolled out nationally, because it is in the rural communities that we have the greatest power to effect change." You can see that change in rugby league particularly, which is Papua New Guinea’s national sport. Tahina has been part of the Papua New Guinea Orchids since their second year. After the Orchids hosted the Jillaroos in 2018, one of Tahina's team-mates told her she didn’t want to take part in a lap of honour because the last time they had played at home, a year earlier, people were spitting at them and throwing empty cans at them. Tahina took that young woman’s hand to support her during the lap of honour. But instead of directing vitriol, people were applauding and asking for autographs. All this in just 12 months. But Tahina recognises there is still plenty of work to do. "Women can contribute to society in a meaningful way and I can have a role in changing people’s perceptions, especially in rural communities about the role women can play in developing our society for the better," she said. Help is available 24/7 for anyone who has mental health issues by calling Lifeline Australia on 13 11 14 Rape & Domestic Violence Services Australia provides 24/7 telephone and online crisis counselling for anyone - women and men - in Australia who has experienced or is at risk of sexual assault, family or domestic violence and their non offending supporters. Junior Reps Academy Sharks tackle the Dogs Morris: They're a dangerous side Sponsored By Autocraze 3 hours ago Round 18 Captain's Run Sharks Women set up Finals clash Johnson ready for Mt Smart and playing alongside Nikora Follow the Sharks	cc/2019-30/en_head_0044.json.gz/line3281
__label__wiki	0.694522	0.694522	Study Shows Legal Representation Essential to Avoiding Deportation (ESPAÑOL) It seems obvious that foreign nationals with legal representation will be able to prove their case and avoid deportation easier than those without. But the first formal study on legal representation of foreign nationals in immigration proceedings proves the validity of that theory. “By reviewing over 1.2 million deportation cases decided across the United States over a six-year period, this report provides an urgent portrait of the lack of counsel in immigration courts,” according to the study issued by the American Immigration Council. “In it, we reveal that 63 percent of all immigrants went to court without an attorney. Detained immigrants were even less likely to obtain counsel — 86 percent attended their court hearings without an attorney. For immigrants held in remote detention centers, access to counsel was even more severely impaired, only 10 percent of immigrants detained in small cities obtained counsel.” Having a lawyer usually provides positive outcomes for foreign nationals in immigration court trials, according to the AIC study titled Access to Counsel in Immigration Court. Foreign nationals in immigration court proceedings have a right to counsel, but the court is not required to appoint an attorney to represent the immigrant if he or she cannot afford to pay for legal representation or cannot obtain pro-bono representation. The AIC study also highlighted the nationalities more likely or less likely to have legal representation. “Mexican immigrants had the highest detention rate (78 percent) and the lowest representation rate (21 percent) of nationalities examined,” the AIC report said. “In contrast, Chinese immigrants had the lowest detention rate (4 percent) and the highest representation rate (92 percent).” According to the report, Haitians and immigrants from India also have a high rate of representation with 71 percent for each nationality. Several factors explain why immigrants of different nationalities are more likely or less likely to obtain representation for proceedings in immigration court, according to the study. “Economic status certainly plays a role since the scarcity of pro bono resources demands that the majority of immigrants who obtain representation must be able to afford an attorney,” according to the study. “The ability to find an attorney could also be influenced by the strength of the social networks that different immigrant groups have to assist them in finding counsel.” Community, Latest Immigration News	cc/2019-30/en_head_0044.json.gz/line3283
__label__wiki	0.874823	0.874823	Australia's most controversial stamp? The Surfing Santa of 1977 By Jacqui Taffel November 18, 2015 — 12.12pm Sonia Kretschmar got an early Christmas present this year. On October 30, her first stamp design was released, a glowing, stylised nativity scene that will adorn millions of Christmas cards sent in Australia. For the Melbourne illustrator and graphic designer, it's a lifelong dream come true. She collected stamps as a child, enthralled by their miniature artistry. "Stamps were a symbol of exotic places, overseas especially. And the really colourful, modernist ones from the '60s and '70s; I loved them." Sonia Kretschmar's traditional Christmas stamp design for 2015, full minisheet. Stamps helped inspire her to become an illustrator. So far in her 20-year career, she has produced artwork for books, magazines and newspapers, created animation, taught design and illustration and had a painting hung in the Archibald Prize. Then in May last year she got an email from Australia Post's philatelic design manager. Each year, Christmas stamps are issued with a mix of traditional and secular designs. Would she be interested in creating something a bit different for the 2015 religious stamp? Nudibranch stamp series designed by Simone Sakinofsky at Australia Post. Kretschmar was thrilled to be asked, but also realistic. She knew it would be a long process involving many critiques and committees before final approval. She had friends whose designs had been archived without being released. She was given the choice between designing separate stamps or a mini-sheet, with stamps cropped from a larger scene; she went for the mini-sheet. The basic rules: each stamp must bear the word "Australia" and the price (the year of issue also appears in micro-type); and the design must include light areas for Australia Post's letter sorting machinery to recognise the stamp. The traditional Christmas stamp has extra rules such as Mary's garb (it must be blue) and a halo for Jesus (compulsory). Above all, it must be respectful. The most controversial stamp was the Surfing Santa of 1977. Australia Post received a huge backlash with complainants saying it did not treat Christmas seriously. The postal service had started producing a mix of secular and religious Christmas stamps just a year earlier. When the Surfing Santa was re-released in 2007 as part of a 50 years of Christmas Stamps issue, there were no complaints. Sonia Kretschmar with her Christmas stamp design for Australia Post. Credit:Sonia Kretschmar Kretschmar's design got through with relative ease. There were a few tweaks – the animals' expressions, the exact blue of Mary's dress – but the query she expected, about her golden Madonna, was never raised. "I wanted to make her skin tone a bit ambiguous, so she's not traditionally like a white Mary, she could be any colour," says Kretschmar. The duck, a small tribute to Melbourne cartoonist Michael Leunig, didn't make it into the stamp crop as it was considered too non-traditional. The stamp business, and stamp collectors, tend to be conservative, says Australia Post's philatelic manager Michael Zsolt. "We see stamps as a record of Australian history, it's a very important part of our role and we take it very seriously," he says. "So we're not in it to make political statements or take sides on any issue." Sonia Kretschmar's traditional Christmas 65 cent stamp design for 2015. Before 1997, no living person apart from the monarch and her family was allowed to appear on Australian stamps. Since then, they have featured Olympic gold medallists, Indigenous leaders and the Living Legends series, which began with Donald Bradman and has included medical scientists, writers, philanthropists, cooks and Australian music legends. This year, it was recipients of the Victoria Cross. To select the legends and make sure each design is accurate, the philatelic team has three inhouse researchers and consults with experts and cultural bodies, though sometimes this advice is queried by zealous collectors and interest groups. The controversial Surfing Santa stamp of 1977, re-released in 2007 by Australia Post. "It can be as simple as putting black colouring on a wasp in slightly the wrong spot," says Zsolt. Last year's Things that Sting children's issue included a European wasp, but its colouring raised conjecture. Experts maintained it was right, but "there's still a bit of to-ing and fro-ing", Zsolt says. The design team does get to have some fun. Another children's issue had glow-in-the-dark ink, with hidden fossils only visible under UV light. Australian children's author and illustrator Graeme Base hid insects in his stamps. This year's Centenary of WWI: Gallipoli stamp issue includes a limited edition mini-sheet incorporating shavings from the Australian War Memorial's Lone Pine tree as part of the printing process, an Australian first. Simone Sakinofsky has worked at Australia Post's design studio for nine years. Asked to nominate some of her favourite stamps, she includes a series of nudibranchs, tiny colourful sea creatures she had never heard of before taking on the project. Rather than using plain photos, she designed an underwater landscape for them to float in, with waves and sand and tiny bubbles when you look closely. Stamps usually have a level of detail most people will never notice, but nothing gets past the collectors; the designers often work with them in mind. "They get out their eye pieces and magnifying glasses and look for the hidden detail," Sakinofsky says. "They'll let us know what they think and what they've found." When creating a stamp, Sakinofsky works at 400 per cent of the actual size. "With stamp design you're learning to communicate on a very, very small platform and there's lot to say," she says. What works at 400 per cent doesn't always work at 100 per cent. "You're always trying to simplify and think of different ways to get your message across." It's still a thrill to see her work outside the office. "Sometimes you open the mailbox and say, 'Oh, I designed that!' Or someone will send you an invitation with your stamp on it." As for Kretschmar's debut stamp, the illustrator confesses she doesn't usually send Christmas cards. "But I guess this year I'll have to."	cc/2019-30/en_head_0044.json.gz/line3287
__label__cc	0.582579	0.417421	5 reasons why you should vote SNP at the EU Elections by the SNP Share this article: 0 Posted on 14 May, 2019 21 May, 2019 Scotland’s future lies in Europe. A vote for the SNP is a vote to make clear Scotland says No to Brexit. Scotland voted overwhelmingly to remain in the EU. It’s a democratic outrage that we’re now being dragged out against our will. Brexit will be bad for Scotland – with fewer jobs, fewer opportunities and households left worse off. The European elections are an opportunity for people in Scotland to make clear they will not stand for Brexit. Labour and the Tories are both committed to delivering Brexit. We need to send them a message. Both Theresa May and Jeremy Corbyn are determined to deliver Brexit at any cost. The SNP has repeatedly proposed a compromise, Norway-style single market option that would minimise the damage caused by Brexit – but we’ve been ignored. Neither Labour nor the Tories can stand up for Scotland and our overwhelming vote to Remain in the EU. We need to send them a message that Scotland says no to Brexit. Brexit is undesirable and undeliverable. We support a second EU referendum, with the option to Remain. Politicians at Westminster haven’t been able to deliver Brexit. But Theresa May thinks she can ask them again and again until they agree with her deal. It’s wrong that MPs get to change their mind but the public can’t. A second EU referendum, with the option to Remain, can solve Westminster’s impasse – and can keep Scotland in the EU. What can’t be allowed to happen is for the UK to crash out of the EU without a deal. Article 50 should be revoked if a no-deal Brexit is the only alternative. Brexit has shown, once and for all, that Westminster isn’t working. The UK political system is deeply dysfunctional and has ground to a halt due to Brexit. The Tories and Labour are both hopelessly divided, with neither party a competent or credible choice. Theresa May is a Prime Minister held hostage by the DUP and by hardliners in her own party – but still unable to make any meaningful progress. Scotland deserves better than a Westminster system that isn’t working. No wonder more and more people believe Scotland’s future should be as an independent country. Of the 27 independent countries that decided the UK’s future at the European Council two weeks ago, around a dozen are smaller than or similar in size to Scotland. The contrast between the solidarity EU countries have shown Ireland, and the lack of respect the UK government has shown Scotland, could not be clearer. We want Scotland to be a decision maker, with a seat at the top table – working constructively and on an equal basis with our European partners. Make Scotland’s voice heard – vote SNP on Thursday 23rd of May.	cc/2019-30/en_head_0044.json.gz/line3288
__label__wiki	0.988682	0.988682	Flying frog among 353 new Himalayan species: WWF Source : AFP Last Updated: Mon, Aug 10, 2009 09:20 hrs A flying frog, the world's smallest deer and the first new monkey to be found in over a century are among 350 new species discovered in the eastern Himalayas in the past decade, the WWF said Monday. But the environmental group said the vital habitats of the mountain range were facing growing pressures from unsustainable development in the region, which spans Nepal, China, India, Bhutan and Myanmar. In a report released here Monday, it said climate change, deforestation, overgrazing by domestic livestock and illegal poaching and wildlife trading threatened one of the biologically richest areas of the planet. "In the last half-century, this area of South Asia has faced a wave of pressures as a result of population growth and the increasing demand for commodities," said the report, "The Eastern Himalayas -- Where Worlds Collide." "Only 25 percent of the original habitats in the region remain intact. For the unique species of the Eastern Himalayas, this means that today 163 are considered globally threatened," it said. The WWF said 353 new species were discovered in the region between 1998 and 2008, among them a red-footed tree frog known as a "flying frog" because its large webbed feet allow it to glide when falling. Another new species was a kind of caecilian, a limbless amphibian that resembles a giant earthworm and lives underground -- a significant discovery because caecilians are among the planet's least-studied creatures. Other highlights were the world's smallest deer -- a miniature muntjac standing just 60-80 centimetres (25-30 inches) tall that was found in northern Myanmar -- and the first new monkey species to be discovered in over a century. The WWF said the new species of macaque was one of the highest-dwelling monkeys in the world, living in India's Arunachal Pradesh state at between 1,600 and 3,500 metres (5,000 and 11,500 feet) above sea level. Among the 242 new plant varieties discovered was an ultramarine blue flower found by two intrepid Chinese botanists who descended into a gorge in Tibet that is twice as deep as the Grand Canyon in places. The WWF described the rare bloom as "dramatic in both colour and form" and said its colour changed with the temperature, making it particularly remarkable. "; var catName="international"; var fullTitleVal="title=flying frog among 353 new himalayan species wwf&cid=jikoOcajdfe"; var fullChannelVal="news";	cc/2019-30/en_head_0044.json.gz/line3289
__label__cc	0.724603	0.275397	Polish Wigilia dinner to be held at St. Nicholas Polish Falcons Heritage Foundation (PFHF) will sponsor its third annual Traditional Wigilia Dinner on Saturday, Dec. 3 at the St. Nicholas Greek Orthodox Cathedral in Oakland from 2 p.m. to 4 p.m. PFA Cultural Commissioner Lawrence Kozlowski will host the event, leading guests in the sharing of Oplatki and other traditions. Singing of Polish Koledy (carols), as well as carols in English, will take place following the meal. The cost of the event is $40 per person and $20 for children 12-and-under. Reservations are required. Doors will open at 1 p.m. This year’s dinner will feature mushroom soup, baked fish, boiled potatoes, pierogi, peas and carrots, noodles and cabbage, cucumbers in sour cream, fruit compote, bread and butter, honey cookies, coffee, tea and soft drinks. In attendance at the event promoting his latest book will be Oscar Swan, a Slavic Languages and Literatures professor at the University of Pittsburgh and author of over 15 books. Mr. Swan was the first American recipient of the Thesaurus Poloniae Award from the Center of International Culture, Krakow. He is also the recipient of the Polonicum Award from the University of Warsaw for outstanding contributions to the promulgation of Polish language, literature, and culture outside Poland. Recently, he received the award for outstanding contributions to Polish culture in America from the American Council for Polish Culture. Also in attendance displaying his art will be David Motak, an internationally recognized artist and graphic designer specializing in the Szopka, an ornate traditional architectural art form that originated in the environs of Kraków, Poland. Mr. Motak’s Szopka creations translate basic materials such as wood, cardboard and colored foiled paper into whimsical, multistory interpretive 3-D structural sculptures that combine a variety of traditional architectural styles into ornate, yet harmonious works of art. For more information regarding the dinner and to make reservations, contact the Polish Falcons at 844-203-9917 or visit polishheritage.org/events. Subscribe to our Business mailing list to receive email only specials	cc/2019-30/en_head_0044.json.gz/line3295
__label__cc	0.744176	0.255824	Latest Productions Chartered Banker – April 10th May 2018 /in Journals, Trade Publishers /by emma https://www.soundunderstanding.co.uk/podcast-player/388/chartered_banker_april.mp3 Download file \| Play in new window \| Duration: 2:06 The latest from Chartered Banker Magazine. The Chartered Banker Institute is the largest professional body for bankers in the UK, with more than 30,000 members students in 87 countries worldwide. It is the oldest banking institute in the world, approved by the UK’s Privy Council to award the “Chartered Banker” designation to qualified members. As a professional body it provides a quarterly audio magazine to its members who are time poor but information hungry and value the word-for-word reading of the print edition. Chartered Bankers ‘on the move’ listen to their specialist information in the car, on a plane, or out for a jog. https://www.soundunderstanding.co.uk/wp-content/uploads/2018/06/sound_understnding_header.jpg 0 0 emma https://www.soundunderstanding.co.uk/wp-content/uploads/2018/06/sound_understnding_header.jpg emma2018-05-10 12:22:142018-10-19 16:15:47Chartered Banker - April Membership Organisations (1) Trade Publishers (1) More audio growth! through smart speakers are proving surprisingly popular with older people as they are less fiddly to use than other technology according to the Times. soundunderstanding.co.uk/indu… © Copyright - Sound Understanding 2018. Sound Understanding Ltd. is registered in England & Wales. Company Registration No. 10582848. Registered Offices: 38 Gay Street, Bath, England, BA1 2NT.	cc/2019-30/en_head_0044.json.gz/line3296
__label__wiki	0.686663	0.686663	Books DUINO ELEGIES Rainer Maria Rilke PreviousWINTERWARD William Stafford NextTHE FIRE'S JOURNEY: PART I Eunice Odio DUINO ELEGIES Rainer Maria Rilke Translated from the German by Gary Miranda Begun in 1912, interrupted by the Great War, and completed early in 1922, the ten meditations on love and death in Rilke’s Duino Elegies are perhaps the twentieth century’s most sustained outpouring of lyricism. Abstract, allusive, and rich with imagery, this sequence has been attempted by many translators. Gary Miranda’s 1981 version, reprinted here in a revised and expanded edition, is unsurpassed in rendering the challenging German text as a lucid and elegant poem in English. "Rilke speaks through Gary Miranda as through a microphone, with an unprecedented combination of utterly transfixing clarity, propulsive urgency, and emotive concentration. Nowhere else in English—nowhere else—have the Elegies achieved such unrelenting, enveloping intensity. This is a mind- and life-altering book. Much more than a translation, this is a work of total reincarnation." —Malachi Black ABOUT RAINER MARIA RILKE Rainer Maria Rilke (1875-1926) is one of the most celebrated poets of the twentieth century. Rilke was born in Prague, lived throughout Europe, and spent his final years in Switzerland, where he wrote the Duino Elegies. He died of leukemia in December 1926. 10 Great Small Press Books Worth Picking Up, by The Seminary Co-op (Literary Hub) ABOUT GARY MIRANDA Gary Miranda was born in Bremerton, Washington, in 1938 and raised in the Pacific Northwest. After three years in Greece as a Fulbright Lecturer in American Literature at the University of Athens, he lived in the Boston area for six years before returning to the Northwest to serve as poet-in-residence for five years at Reed College in Portland, Oregon, where he currently lives. Miranda’s poems have appeared in journals including The New Yorker, Poetry, Atlantic Monthly, and American Poetry Review, and have received numerous awards and wide critical praise. His poetry collections include Listeners at the Breathing Place (Princeton University Press, 1979), nominated for a Pulitzer Prize, Grace Period (Princeton University Press, 1983), and Turning Sixty (Zoland Books, 2003). 80 pages \| 5.5 x 7.5 in. ISBN-13: 978-1-935635-32-1 (paperback) ISBN-13: 978-1-935635-33-8 (hardcover) Select Format paperbackhardcover	cc/2019-30/en_head_0044.json.gz/line3298
__label__cc	0.642744	0.357256	Cutting-edge power and great usability from this consumer level laptop By Alex Bentley 2010-03-11T10:00:00.69Z Laptops and netbooks The Dell Inspiron 1564 is one of the first laptops to use the Core i3 in laptop trim Apart from the weak networking options, the Inspiron 1564 is a great all-round machine that is packed with cutting-edge components Powerful Core i3 CPU Good screen Decent usability Decent 3D performance Limited network connectivity Dell has had an impressive track record over the past year, delivering one stunning consumer laptop after another. The Inspiron 1564 continues this run of success by implementing cutting-edge technology in this powerful and well-rounded machine. Built around a processor from Intel's Core i3 range, this is among the most powerful entry-level laptops we've seen to date. Effortlessly outperforming all but the similarly specified Samsung R580, multi-tasking with even more demanding software is possible. 3D performance Despite using an integrated GPU – a graphics technology traditionally associated with limited power – Intel's latest onboard chip provides surprisingly powerful 3D performance, allowing high-definition (HD) video and even less demanding games to run with little effort. The stunning 15.6-inch screen adds to the multimedia usability on offer. It is a very bright panel, and delivers fantastic colour reproduction and sharp images, ensuring movies, photos and games are shown with impressive clarity and vibrancy. With such powerful performance on offer, we expected mobility to suffer as a result, but this wasn't the case. Running for an impressive 203 minutes under battery power, you can comfortably keep working away from mains power – made easier by the light 2.5kg chassis. The stylish design of the previous Inspiron 15 range has remained relatively intact here, but Dell has added a faux brushed aluminium finish to the plastic interior. While it is a subtle touch, it creates a sleek, high-end look that belies this machine's comparatively low price tag. The keyboard is another high point. While it lacks the backlighting of more expensive models, all keys are large, accurate and responsive, making it easy and comfortable to type over long periods. Unfortunately, network connectivity is more basic than we would have liked. While some rivals provide high-speed wireless and fixed access, an older and slower technology is used here. Speeds will suit basic home use, but it is worth bearing in mind before buying. More pleasingly, storage is excellent. The 500GB hard drive will hold all your family's data with ease. Comprehensive support for flash storage cards is also provided. Continuing Dell's recent run of success, the Inspiron 1564 is an impressively powerful and portable machine. While its limited network connectivity is disappointing, it excels in all other areas, making it one of the best entry-level laptops we've seen this year. Follow TechRadar Reviews on Twitter: http://twitter.com/techradarreview The best Amazon Prime Day deals 2019: US Edition	cc/2019-30/en_head_0044.json.gz/line3300
__label__cc	0.567838	0.432162	Keeping social enterprise going gives a warm glow By Stuart Laundy - Senior Reporter • 10 Feb 2019 KNIT AND NATTER: Volunteers at the Warm Age Wood Company. Seated, from left, are Mary O'Connor, Margaret Forsyth and Muriel Gilson. Standing behind are Rosie Pirrie and Sue Overton. A GROUP of volunteer knitters say ensuring the continued success of a social enterprise committed to keeping people warm is the best possible tribute to the project’s late founder. Dave Watson launched The Warm Age Wood Company, in Barnard Castle, five years ago. Sadly, he died in late 2017 of pancreatic cancer. The enterprise provides wood briquettes for those in fuel poverty. It does this through the general sale of briquettes – with one bag provided free to those in need for every ten sold – and money raised through the sale of woollen items knitted by volunteers. Figures for 2017/18 show the company sold 1,305 bags of briquettes and since last September another 774. This means more than 200 free bags of briquettes have been provided to those in fuel poverty during that period. In addition, last year 496 items knitted by the team of more than 20 volunteers were sold. This included 249 hats, 48 pairs of mittens and gloves and 25 dog coats, while woolly vests, cardigans and jumpers, tea cosies, socks and a host of other pieces of knitwear helped raise funds to buy more briquettes. Volunteer Margaret Forsyth said: “It’s a good tribute to Dave. He would be really pleased that we have been able to keep it going.” Fellow volunteer Mary O’Connor said that after five years, the group was keen to remind people that the Warm Age Wood Company outlet was “more than just a wool shop”. She said that while many in the town are aware of the enterprise, others who are new to the area or just visiting may not know how it operates. The group of volunteer knitters come from near and far, with one member based in Kendal and another in London. Ms O'Connor also visits knitters who live in the vicinity but are unable to get into the shop, delivering wool and fetching the finished items. Ms Forsyth was keen to point out that only pure wool is used to make the items sold at the shop. “We knit small stuff – children’s jumpers, hats, scarves, gloves, etc. We have also invented a Barney beanie,” she said. “We want to thank GSK, The Bowes Museum and Teesdale U3A for their generous donations and also our regular customers who support us and buy our products. When you buy from us, you keep other warm and the more we sell, the more briquettes we can give away.” Ms Forsyth added: “So far this season, we have supported eight people in three homes. One of those expressed his thanks saying the delivery came just at the right time and that it lifted his spirits and kept him warm.” Those in need of help from the Warm Age Wood Company are identified through community organisations, day clubs, food banks, advice centres and other groups and are referred to the enterprise. The company began life by taking a stall at Barnard Castle Market before moving into the shop in October 2016. The shop is open from 10am to 4pm Wednesday to Saturday. It also opens “unofficially” on a Tuesday morning when the volunteers get together for a knit and natter session over a cuppa. “We have a link with No 15 cafe. Quite often when people come, we will go through and order and they will come with a tray of coffee,” said Ms Forsyth.	cc/2019-30/en_head_0044.json.gz/line3302
__label__cc	0.622947	0.377053	British entrepreneurs should feel upbeat about the post-EU future Haakon Overli 3 June 2017 • 2:36pm Last year saw more people in Britain launch their own businesses than ever before Credit: Getty Images Once the General Election is out of the way, how will we position ourselves as entrepreneurs for the next two years, as Britain prepares to leave the European Union – and how will the Government support wealth creation? Well, while the election campaign has inevitably focused on many of the dangers and challenges posed by Brexit, we should not feel unduly pessimistic: the reality is that there are huge opportunities for British innovators to exploit in the years ahead – and the process of change will create even more of these openings. There is every reason to be upbeat. Despite the uncertainties of the political and economic climate, last year saw more people in Britain launch their own businesses...	cc/2019-30/en_head_0044.json.gz/line3303
__label__wiki	0.981175	0.981175	Indian woman gives birth at age of 70 An Indian woman has given birth to her first child at the age of 70 after receiving fertility treatment. 1:39PM GMT 08 Dec 2008 Rajo Devi, who married 50 years ago, gave birth to a baby girl on November 28, and is now thought to be the world's oldest new mother. Dr Anurag Bishnoi, a doctor at the Hisar fertility centre in Haryana state, said: "Rajo Devi and (her husband) Bala Ram approached the centre for treatment and the embryo transfer was done on April 19. "Both the mother and child are in good health." A 67-year-old Spanish woman who had twins in 2006 was thought to have been the previous oldest mother. Devi's husband, aged 72, had also wed his wife's sister after 10 years of his first marriage did not result in children. His second wife also failed to become pregnant. World's oldest mothers Indian woman has first child at age of 70 It was not clear whose egg and sperm were used in the successful treatment. Dr Bishnoi, who helped the couple realise their dream, said both the mother and child were in good health. "IVF has revolutionised the way we look at infertility," said Mr Bishnoi. "Infertility is no longer a social taboo or a divine curse. It can be treated scientifically." "Adriana Iliescu, a retired university lecturer in Romania, was the oldest woman to have given birth. She delivered at the age of 66 in 2006. Maria Del, a Spanish woman, gave birth by the IVF treatment at the age of 67. And now, Rajo Devi has become the oldest woman to have given birth and the first woman in her seventies to do so," claimed Dr Bishnoi. "Another woman of her age is reported to have delivered a child at Muzzafarnagar, but she was previously fertile," he added. New mother Rajo Devi, "We longed for a child all these years and now we are very happy to have one in the twilight years of our life." Husband Ram said he wasn't worrying over who would look after the child if they died. "The upbringing of the child is not a problem. We have a joint family as is common in rural Haryana," he said. The couple said they were facing social stigma for being childless for the last 55 years. "We used the usual intra cytoplasmic sperm injection (ICSI) technique in her case. The ICSI method enables even poor quality sperms being used creating embryos," said Dr Bishnoi. He said his parents and wife, all doctors, performed the procedure together. "The major concern for us was that in case the woman conceived twins, she may not be able to carry them through the full term of pregnancy. In that case, all over efforts would have failed and the woman's life would have been in danger," Bishnoi said. To avoid multiple pregnancies, the doctors used blastocyst culture, where a single potential embryo is transferred to the uterus instead of the normal two to three embryos. "This embryo is transferred after five days in this technique, while in normal cases it is done in two-three days," he added. "Rajo is the eldest of four siblings. She is elder to me by about 16 years. We all prayed she would get a child and even married our other sister to Bala Ram in this hope. Now the whole family is very happy that she has a child," said Chand Ram, Rajo Devi's brother who is a sub inspector in Haryana Police at Panchkula. Telegraph TV » India's Republic Day Stories of courage Chennai floods, in pictures Narendra Modi visits Britain The Kumbh Mela Power to the people Cannibal monks	cc/2019-30/en_head_0044.json.gz/line3304
__label__cc	0.721959	0.278041	Politics & Government› Terrorism impact on the travel industry in the United States Terrorism impact on tourism in the U.S. - Statistics & Facts Published by Statista Research Department, Aug 27, 2018 Tourism has long been negatively affected by unpredictable events. Financial crises, health epidemics, natural disasters and political unrest can all have negative impacts on the tourism industry. Since the 9/11 attacks, perpetrated by Al Qaeda, terrorism has gained unprecedented media attention and has become a source of anxiety for people around the world. Although terrorism has been in existence for many years, the number of suicide attacks globally has increased in the years since 9/11, with a record 652 suicide terrorist attacks in 2015. In the United States, the fear of terrorism led newly elected President Donald Trump to issue an executive order which temporally banned entrance to the United States for citizens of seven Muslim Majority countries (Iran, Iraq, Syria, Yemen, Somalia, Sudan, and Libya). The order titled ‘Protecting the Nation from Foreign Terrorist Entry into the United States’ was critically dubbed the ‘Muslim Ban’ by the media. The effect of the ban had an immediate impact on the growth of net air bookings from the seven banned countries, with an 80 percent decrease in flight booking between January 28 and February 4, 2017. The ban affected countries were not the only ones which experienced a drop in bookings. In fact, only two regions (Central and Eastern Europe) experienced booking growth, all others including Northern and Western Europe, Asia-Pacific, and the Middle East and Africa, decreased their air travel to the United States. The ban was blocked by the courts, as it was deemed unconstitutional, and a newly revised version of the legislation was reintroduced in March 2017 with residents from six of the original countries remaining banned. This was problematic for many travel managers in the United States who were concerned that this legislation would make travel more difficult for U.S. citizens. It was also problematic for the tourism industry in the U.S., because in 2015, the majority of travelers from the six banned countries were visiting as either leisure or business tourists, with student entries, temporary workers and those arriving on fiancé visas accounting for less than half of the tourist numbers. Travel manager’s fears may have been well founded as the way in which Americans travel have indeed been impacted by terrorism. In 2017, terrorism and / or terror warnings were the leading factors affecting the travel preferences of U.S. adults. That said, the largest share of U.S. travelers stated that they would not avoid any specific European country as a result of terrorist activities. Around 27 percent of these respondents specifically stated that they would not allow fear to dictate their travels. Travel agency workers are also reporting similar sentiments. After the attacks in France, around 35 percent of their clients continued unchanged with their current planned trips. Although some had chosen to delay their travel, less than 10 percent reported having clients cancelling their trips. This text provides general information. Statista assumes no liability for the information given being complete or correct. Due to varying update cycles, statistics can display more up-to-date data than referenced in the text. Interesting statistics In the following 4 chapters, you will quickly find the 23 most important statistics relating to "Terrorism impact on the travel industry in the United States". Statistics on the topic U.S. travelers Effect of U.S. travel ban European travelers Effect of terrorism on travel bookings to Europe People killed due to terrorist attacks Number of people injured due to terrorist attacks Iraq suffered from the most terrorist attacks Factors that have some or a strong influence on U.S. adults' travel preferences 2017 Agreement score of travelers regarding select statements worldwide 2016 Events that may affect travel agency revenue in the next 2 years in the U.S. 2017 European countries U.S. travelers would avoid in 2016 Effect of Paris terror attacks on U.S. travelers vacation plans to France 2016 Willingness of U.S. travel agents to vacation in Paris since the 2015 terror attacks Show all statistics (6) Number of visitors from the six travel ban countries to the U.S. in 2015 by visa type Growth of net bookings to the U.S. during the first travel ban in 2017, by region Leading concerns of U.S. travel managers regarding the March 2017 travel ban U.S. public opinion on banning immigration of Muslims in 2017, by political ideology U.S. public opinion on intent of EO banning immigrants from Muslim majority countries Impact of external factors on holiday plans in the European Union 2015 Impact of terrorism on holiday travel plans in Europe 2015, by country Summer holiday travel: countries avoided due to risk of terror attacks in Spain 2016 Italy: terrorism fear influencing vacations summer 2016 Italy: influence of terrorist attacks on holiday choices 2016, by age Change in flight bookings to Brussels after terror attack March 2016 Change in flight bookings to Paris after Brussels terror attack March 2016 Change in flight bookings to Berlin after Brussels terror attack March 2016 Change in flight bookings to Munich after Brussels terror attack March 2016 Change in flight bookings to Zurich after Brussels terror attack March 2016 Change in flight bookings to Amsterdam after Brussels terror attack March 2016 Change in flight bookings to Rome after Brussels terror attack March 2016 Dossier on the topic All important statistics are prepared by our experts – available for direct download as PPT & PDF! Go to report Important key figures The most important key figures provide you with a compact summary of the topic of "Terrorism impact on the travel industry in the United States" and take you straight to the corresponding statistics. Terrorism in the U.S. Terrorist attacks that happened on U.S. territory in 2017 Detailed statistics Total number of terrorist attacks in the United States between 1995 and 2017 People killed due to terrorist attacks in the U.S. in 2017 Total number of terrorist attack fatalities in the United States from 1995 to 2017 Number bombing terrorist attacks in the U.S. since 1970 Terrorist attacks in the United States from 1970 to 2017, by attack type Number of terrorists in the U.S. who were born citizens Residency status of terrorists in the United States since 9/11, as of 2019 Show more factsHide Travel and Tourism in the U.S. Number of domestic leisure trips in the U.S. 1.79bn Number of domestic leisure and business trips in the U.S. 2008-2022 Number of outbound tourists from the U.S. Number of outbound tourists from the U.S. 2002-2017 Business travel spending in the U.S. in 2016 283.62bn USD Business travel spending in the U.S. 2011-2017 Effect of Terrorism on U.S. travelers Share of Americans whose travel preferences are influenced by terrorism Share of U.S. travel agents who think terrorism fears could affect agency revenue Share of Americans who have been scared for their health or safety on a business trip Distribution of business travelers who have felt in danger on a trip in the U.S. 2015 Share of Americans who are afraid to fly because of terrorist attacks American air travelers - reasons against flying 2017 More interesting topics from the industry "National Security" Global Tourism Industry Travel and Tourism Industry in the U.S. Terrorism impact on the travel industry in Europe Islamic State (ISIS) Other studies on the topic Terrorism in the United Kingdom Terrorism in the European Union	cc/2019-30/en_head_0044.json.gz/line3306
__label__cc	0.662137	0.337863	Gregory Enns, MD Director, Biochemical Genetics Program Add to contacts (vCard) Mary L. Johnson Specialty Services 730 Welch Road Map, Directions & Parking Work and Education University of St Andrews, St. Andrews, Scotland, 12/31/1990 Children's Hospital Los Angeles Pediatric Residency, Los Angeles, CA, 06/30/1992 UCSF Medical Center, San Francisco, CA, 06/30/1998 Clinical Biochemical Genetics, American Board of Medical Genetics and Genomics Clinical Genetics, American Board of Medical Genetics and Genomics View my Stanford Medicine academic profile Neurometabolic Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy PLOS ONE Kahn-Kirby, A. H., Amagata, A., Maeder, C. I., Mei, J. J., Sideris, S., Kosaka, Y., Hinman, A., Malone, S. A., Bruegger, J. J., Wang, L., Kim, V., Shrader, W. D., Hoff, K. G., Latham, J. C., Ashley, E. A., Wheeler, M. T., Bertini, E., Carrozzo, R., Martinelli, D., Dionisi-Vici, C., Chapman, K. A., Enns, G. M., Gahl, W., Wolfe, L., Saneto, R. P., Johnson, S. C., Trimmer, J. K., Klein, M. B., Holst, C. R. 2019; 14 (3) View details for DOI 10.1371/journal.pone.0214250 Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder AMERICAN JOURNAL OF HUMAN GENETICS Olahova, M., Yoon, W., Thompson, K., Jangam, S., Fernandez, L., Davidson, J. M., Kyle, J. E., Grove, M. E., Fisk, D. G., Kohler, J. N., Holmes, M., Dries, A. M., Huang, Y., Zhao, C., Contrepois, K., Zappala, Z., Fresard, L., Waggott, D., Zink, E. M., Kim, Y., Heyman, H. M., Stratton, K. G., Webb-Robertson, B. M., Snyder, M., Merker, J. D., Montgomery, S. B., Fisher, P. G., Feichtinger, R. G., Mayr, J. A., Hall, J., Barbosa, I. A., Simpson, M. A., Deshpande, C., Waters, K. M., Koeller, D. M., Metz, T. O., Morris, A. A., Schelley, S., Cowan, T., Friederich, M. W., McFarland, R., Van Hove, J. K., Enns, G. M., Yamamoto, S., Ashley, E. A., Wangler, M. F., Taylor, R. W., Bellen, H. J., Bernstein, J. A., Wheeler, M. T., Undiagnosed Diseases Network 2018; 102 (3): 494504 ATP synthase, H+ transporting, mitochondrial F1 complex, subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of F1FO ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsyn, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Ourdata establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation. Glutathione as a Redox Biomarker in Mitochondrial Disease-Implications for Therapy. Journal of clinical medicine Enns, G. M., Cowan, T. M. 2017; 6 (5) Technical advances in the ability to measure mitochondrial dysfunction are providing new insights into mitochondrial disease pathogenesis, along with new tools to objectively evaluate the clinical status of mitochondrial disease patients. Glutathione (l--glutamyl-l-cysteinylglycine) is the most abundant intracellular thiol, and the intracellular redox state, as reflected by levels of oxidized (GSSG) and reduced (GSH) glutathione, as well as the GSH/GSSG ratio, is considered to be an important indication of cellular health. The ability to quantify mitochondrial dysfunction in an affected patient will not only help with routine care, but also improve rational clinical trial design aimed at developing new therapies. Indeed, because multiple disorders have been associated with either primary or secondary deficiency of the mitochondrial electron transport chain and redox imbalance, developing mitochondrial therapies that have the potential to improve the intracellular glutathione status has been a focus of several clinical trials over the past few years. This review will also discuss potential therapies to increase intracellular glutathione with a focus on EPI-743 (-tocotrienol quinone), a compound that appears to have the ability to modulate the activity of oxidoreductases, in particular NAD(P)H:quinone oxidoreductase 1. View details for DOI 10.3390/jcm6050050 Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nature communications Gomez-Ospina, N., Potter, C. J., Xiao, R., Manickam, K., Kim, M., Kim, K. H., Shneider, B. L., Picarsic, J. L., Jacobson, T. A., Zhang, J., He, W., Liu, P., Knisely, A. S., Finegold, M. J., Muzny, D. M., Boerwinkle, E., Lupski, J. R., Plon, S. E., Gibbs, R. A., Eng, C. M., Yang, Y., Washington, G. C., Porteus, M. H., Berquist, W. E., Kambham, N., Singh, R. J., Xia, F., Enns, G. M., Moore, D. D. 2016; 7: 10713-? Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. View details for DOI 10.1038/ncomms10713 A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency NEW ENGLAND JOURNAL OF MEDICINE Burton, B. K., Balwani, M., Feillet, F., Baric, I., Burrow, T. A., Camarena Grande, C., Coker, M., Consuelo-Sanchez, A., Deegan, P., Di Rocco, M., Enns, G. M., Erbe, R., Ezgu, F., Ficicioglu, C., Furuya, K. N., Kane, J., Laukaitis, C., Mengel, E., Neilan, E. G., Nightingale, S., Peters, H., Scarpa, M., Schwab, K. O., Smolka, V., Valayannopoulos, V., Wood, M., Goodman, Z., Yang, Y., Eckert, S., Rojas-Caro, S., Quinn, A. G. 2015; 373 (11): 1010-1020 Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia.In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile.Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment.Sebelipase alfa therapy resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency. (Funded by Synageva BioPharma and others; ARISE ClinicalTrials.gov number, NCT01757184.). View details for DOI 10.1056/NEJMoa1501365 Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genetics in medicine Parikh, S., Goldstein, A., Koenig, M. K., Scaglia, F., Enns, G. M., Saneto, R., Anselm, I., Cohen, B. H., Falk, M. J., Greene, C., Gropman, A. L., Haas, R., Hirano, M., Morgan, P., Sims, K., Tarnopolsky, M., van Hove, J. L., Wolfe, L., DiMauro, S. 2015; 17 (9): 689-701 The purpose of this statement is to review the literature regarding mitochondrial disease and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are engaged in diagnosing and treating these patients.The Writing Group members were appointed by the Mitochondrial Medicine Society. The panel included members with expertise in several different areas. The panel members utilized a comprehensive review of the literature, surveys, and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve.Consensus-based recommendations are provided for the diagnosis and treatment of mitochondrial disease.The Delphi process enabled the formation of consensus-based recommendations. We hope that these recommendations will help standardize the evaluation, diagnosis, and care of patients with suspected or demonstrated mitochondrial disease.Genet Med 17 9, 689-701. View details for DOI 10.1038/gim.2014.177 Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. journal of pediatrics Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-61 e1 To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA).A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford.Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 1492 mol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 154 mol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 108 mol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning.LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life. View details for DOI 10.1016/j.jpeds.2015.01.051 Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway GENETICS IN MEDICINE Enns, G. M., Shashi, V., Bainbridge, M., Gambello, M. J., Zahir, F. R., Bast, T., Crimian, R., Schoch, K., Platt, J., Cox, R., Bernstein, J. A., Scavina, M., Walter, R. S., Bibb, A., Jones, M., Hegde, M., Graham, B. H., Need, A. C., Oviedo, A., Schaaf, C. P., Boyle, S., Butte, A. J., Chen, R., Clark, M. J., Haraksingh, R., Cowan, T. M., He, P., Langlois, S., Zoghbi, H. Y., Snyder, M., Gibbs, R. A., Freeze, H. H., Goldstein, D. B. 2014; 16 (10): 751-758 Purpose:The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.Methods:Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data.Results:All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele.Conclusion:NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.Genet Med advance online publication 20 March 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.22. View details for DOI 10.1038/gim.2014.22 Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway. Genetics in medicine Enns, G. M., Shashi, V., Bainbridge, M., Gambello, M. J., Zahir, F. R., Bast, T., Crimian, R., Schoch, K., Platt, J., Cox, R., Bernstein, J. A., Scavina, M., Walter, R. S., Bibb, A., Jones, M., Hegde, M., Graham, B. H., Need, A. C., Oviedo, A., Schaaf, C. P., Boyle, S., Butte, A. J., Chen, R., Clark, M. J., Haraksingh, R., Cowan, T. M., He, P., Langlois, S., Zoghbi, H. Y., Snyder, M., Gibbs, R. A., Freeze, H. H., Goldstein, D. B. 2014; 16 (10): 751-758 Degree of Glutathione Deficiency and Redox Imbalance Depend on Subtype of Mitochondrial Disease and Clinical Status PLOS ONE Enns, G. M., Moore, T., Le, A., Atkuri, K., Shah, M. K., Cusmano-Ozog, K., Niemi, A., Cowan, T. M. 2014; 9 (6) Mitochondrial disorders are associated with decreased energy production and redox imbalance. Glutathione plays a central role in redox signaling and protecting cells from oxidative damage. In order to understand the consequences of mitochondrial dysfunction on in vivo redox status, and to determine how this varies by mitochondrial disease subtype and clinical severity, we used a sensitive tandem mass spectrometry assay to precisely quantify whole blood reduced (GSH) and oxidized (GSSG) glutathione levels in a large cohort of mitochondrial disorder patients. Glutathione redox potential was calculated using the Nernst equation. Compared to healthy controls (n = 59), mitochondrial disease patients (n = 58) as a group showed significant redox imbalance (redox potential -251 mV 9.7, p<0.0001) with an increased level of oxidation by 9 mV compared to controls (-260 mV 6.4). Underlying this abnormality were significantly lower whole blood GSH levels (p = 0.0008) and GSH/GSSG ratio (p = 0.0002), and significantly higher GSSG levels (p<0.0001) in mitochondrial disease patients compared to controls. Redox potential was significantly more oxidized in all mitochondrial disease subgroups including Leigh syndrome (n = 15), electron transport chain abnormalities (n = 10), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (n = 8), mtDNA deletion syndrome (n = 7), mtDNA depletion syndrome (n = 7), and miscellaneous other mitochondrial disorders (n = 11). Patients hospitalized in metabolic crisis (n = 7) showed the greatest degree of redox imbalance at -242 mV 7. Peripheral whole blood GSH and GSSG levels are promising biomarkers of mitochondrial dysfunction, and may give insights into the contribution of oxidative stress to the pathophysiology of the various mitochondrial disorders. In particular, evaluation of redox potential may be useful in monitoring of clinical status or response to redox-modulating therapies in clinical trials. CORRELATION OF GLUTATHIONE REDOX POTENTIAL WITH MITOCHONDRIAL DISEASE ETIOLOGY AND CLINICAL SEVERITY Enns, G. M., Moore, T., Le, A., Atkuri, K., Shah, M. K., Cusmano-Ozog, K., Nierni, A., Cowan, T. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2014: 268 Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status. PloS one Enns, G. M., Moore, T., Le, A., Atkuri, K., Shah, M. K., Cusmano-Ozog, K., Niemi, A., Cowan, T. M. 2014; 9 (6) A new LC-MS/MS method for the clinical determination of reduced and oxidized glutathione from whole blood. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Moore, T., Le, A., Niemi, A., Kwan, T., Cusmano-Ozog, K., Enns, G. M., Cowan, T. M. 2013; 929: 51-55 Reduced levels of glutathione (-glutamylcysteinylglycine, GSH) and the ratio of GSH to glutathione disulfide (GSSG) can serve as important indicators of oxidative stress and disease risk. Measured concentrations of GSH and GSSG vary widely between laboratories, largely due to the instability of GSH during sample handling and variables arising from different analytical methods. We have developed a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring whole blood GSH and GSSG that minimizes preanalytic and analytic variability, reliably eliminates interference from ion suppression, and can easily be implemented in clinical laboratories. Samples were deproteinized with sulfosalicylic acid (SSA) and derivatized with N-ethylmaleimide (NEM) in a single preparative step, and the resulting supernatants combined with stable-isotope internal standards (GSH-(13)C, (15)N-NEM and GSSG-(13)C,(15)N), subjected to chromatographic separation using a Hypercarb column, and analyzed by MS/MS in the positive-ion mode. Results showed excellent linearity for both GSH and GSSG over the ranges of physiologic normal, with inter- and intra-assay CV's of 3.1-4.3% and accuracy between 95% and 101%. The lower limits of detection (LLOD) were 0.4M for GSH and 0.1M for GSSG and the lower limits of quantitation (LLOQ) were 1.5M for GSH and 0.1M for GSSG. Derivatized samples are stable for at least 3 years when stored at -80C, and underivatized samples for at least 24h at either 4C or room temperature. Reference intervals were determined for 59 control samples, and were (meanSD): GSH 900140M; GSSG 1.170.43M; GSH/GSSG 880370. View details for DOI 10.1016/j.jchromb.2013.04.004 Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease MOLECULAR GENETICS AND METABOLISM Blankenberg, F. G., Kinsman, S. L., Cohen, B. H., Goris, M. L., Spicer, K. M., Perlman, S. L., Krane, E. J., Kheifets, V., Thoolen, M., Miller, G., Enns, G. M. 2012; 107 (4): 690-699 While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, *p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population. View details for DOI 10.1016/j.ymgme.2012.09.023 Leigh syndrome caused by a novel m.4296G > A mutation in mitochondrial tRNA isoleucine MITOCHONDRION Cox, R., Platt, J., Chen, L. C., Tang, S., Wong, L., Enns, G. M. 2012; 12 (2): 258-261 Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome. View details for DOI 10.1016/j.mito.2011.09.006 Initial experience in the treatment of inherited mitochondrial disease with EPI-743 MOLECULAR GENETICS AND METABOLISM Enns, G. M., Kinsman, S. L., Perlman, S. L., Spicer, K. M., Abdenur, J. E., Cohen, B. H., Amagata, A., Barnes, A., Kheifets, V., Shrader, W. D., Thoolen, M., Blankenberg, F., Miller, G. 2012; 105 (1): 91-102 Inherited mitochondrial respiratory chain disorders are progressive, life-threatening conditions for which there are limited supportive treatment options and no approved drugs. Because of this unmet medical need, as well as the implication of mitochondrial dysfunction as a contributor to more common age-related and neurodegenerative disorders, mitochondrial diseases represent an important therapeutic target. Thirteen children and one adult with genetically-confirmed mitochondrial disease (polymerase deficiency, n=4; Leigh syndrome, n=4; MELAS, n=3; mtDNA deletion syndrome, n=2; Friedreich ataxia, n=1) at risk for progressing to end-of-life care within 90 days were treated with EPI-743, a novel para-benzoquinone therapeutic, in a subject controlled, open-label study. Serial measures of safety and efficacy were obtained that included biochemical, neurological, quality-of-life, and brain redox assessments using technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) radionuclide imaging. Twelve patients treated with EPI-743 have survived; one polymerase deficiency patient died after developing pneumonia and one patient with Surf-1 deficiency died after completion of the protocol. Of the 12 survivors, 11 demonstrated clinical improvement, with 3 showing partial relapse, and 10 of the survivors also had an improvement in quality-of-life scores at the end of the 13-week emergency treatment protocol. HMPAO SPECT scans correlated with clinical response; increased regional and whole brain HMPAO uptake was noted in the clinical responders and the one subject who did not respond clinically had decreased regional and whole brain HMPAO uptake. EPI-743 has modified disease progression in >90% of patients in this open-label study as assessed by clinical, quality-of-life, and non-invasive brain imaging parameters. Data obtained herein suggest that EPI-743 may represent a new drug for the treatment of inherited mitochondrial respiratory chain disorders. Prospective controlled trials will be undertaken to substantiate these initial promising observations. Furthermore, HMPAO SPECT imaging may be a valuable tool for the detection of central nervous system redox defects and for monitoring response to treatments directed at modulating abnormal redox. High-quality DNA sequence capture of 524 disease candidate genes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Shen, P., Wang, W., Krishnakumar, S., Palm, C., Chi, A., Enns, G. M., Davis, R. W., Speed, T. P., Mindrinos, M. N., Scharfe, C. 2011; 108 (16): 6549-6554 The accurate and complete selection of candidate genomic regions from a DNA sample before sequencing is critical in molecular diagnostics. Several recently developed technologies await substantial improvements in performance, cost, and multiplex sample processing. Here we present the utility of long padlock probes (LPPs) for targeted exon capture followed by array-based sequencing. We found that on average 92% of 5,471 exons from 524 nuclear-encoded mitochondrial genes were successfully amplified from genomic DNA from 63 individuals. Only 144 exons did not amplify in any sample due to high GC content. One LPP was sufficient to capture sequences from <100-500 bp in length and only a single-tube capture reaction and one microarray was required per sample. Our approach was highly reproducible and quick (<8 h) and detected DNA variants at high accuracy (false discovery rate 1%, false negative rate 3%) on the basis of known sample SNPs and Sanger sequence verification. In a patient with clinical and biochemical presentation of ornithine transcarbamylase (OTC) deficiency, we identified copy-number differences in the OTC gene at exon-level resolution. This shows the ability of LPPs to accurately preserve a sample's genome information and provides a cost-effective strategy to identify both single nucleotide changes and structural variants in targeted resequencing. View details for DOI 10.1073/pnas.1018981108 Novel Deoxyguanosine Kinase Gene Mutations and Viral Infection Predispose Apparently Healthy Children to Fulminant Liver Failure JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Shieh, J. T., Berquist, W. E., Zhang, Q., Chou, P., Wong, L. C., Enns, G. M. 2009; 49 (1): 130-132 Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes PLOS COMPUTATIONAL BIOLOGY Scharfe, C., Lu, H. H., Neuenburg, J. K., Allen, E. A., Li, G., Klopstock, T., Cowan, T. M., Enns, G. M., Davis, R. W. 2009; 5 (4) Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes. View details for DOI 10.1371/journal.pcbi.1000374 Inherited disorders affecting mitochondrial function are associated with glutathione deficiency and hypocitrullinemia PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Atkuri, K. R., Cowan, T. M., Kwan, T., Ng, A., Herzenberg, L. A., Herzenberg, L. A., Enns, G. M. 2009; 106 (10): 3941-3945 Disorders affecting mitochondria, including those that directly affect the respiratory chain function or result from abnormalities in branched amino acid metabolism (organic acidemias), have been shown to be associated with impaired redox balance. Almost all of the evidence underlying this conclusion has been obtained from studies on patient biopsies or animal models. Since the glutathione (iGSH) system provides the main protection against oxidative damage, we hypothesized that untreated oxidative stress in individuals with mitochondrial dysfunction would result in chronic iGSH deficiency. We confirm this hypothesis here in studies using high-dimensional flow cytometry (Hi-D FACS) and biochemical analysis of freshly obtained blood samples from patients with mitochondrial disorders or organic acidemias. T lymphocyte subsets, monocytes and neutrophils from organic acidemia and mitochondrial patients who were not on antioxidant supplements showed low iGSH levels, whereas similar subjects on antioxidant supplements showed normal iGSH. Measures of iROS levels in blood were insufficient to reveal the chronic oxidative stress in untreated patients. Patients with organic acidemias showed elevated plasma protein carbonyls, while plasma samples from all patients tested showed hypocitrullinemia. These findings indicate that measurements of iGSH in leukocytes may be a particularly useful biomarker to detect redox imbalance in mitochondrial disorders and organic acidemias, thus providing a relatively non-invasive means to monitor disease status and response to therapies. Furthermore, studies here suggest that antioxidant therapy may be useful for relieving the chronic oxidative stress that otherwise occurs in patients with mitochondrial dysfunction. Survival after treatment with phenylacetate and benzoate for urea-cycle disorders NEW ENGLAND JOURNAL OF MEDICINE Enns, G. M., Berry, S. A., Berry, G. T., Rhead, W. J., Brusilow, S. W., Hamosh, A. 2007; 356 (22): 2282-2292 The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects.We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia.Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, P<0.001). Patients 12 or more years of age (93 patients), who had 437 episodes, were more likely than all younger patients to survive (99%, P<0.001). Eighty-one percent of patients who were comatose at admission survived. Patients less than 30 days of age with a peak ammonium level above 1000 micromol per liter (1804 microg per deciliter) were least likely to survive a hyperammonemic episode (38%, P<0.001). Dialysis was also used in 56 neonates during 60% of episodes and in 80 patients 30 days of age or older during 7% of episodes.Prompt recognition of a urea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate. Molecular-clinical correlations in a family with variable tissue mitochondrial DNA T8993G mutant load MOLECULAR GENETICS AND METABOLISM Enns, G. M., Bai, R., Beck, A. E., Wong, L. 2006; 88 (4): 364-371 Unlike many pathogenic mitochondrial DNA mutations, the T8993G mutation associated with Leigh syndrome (LS) and neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP) typically shows little variation in mutant load between different tissue types. We describe the molecular and clinical findings in a family with variable disease severity and tissue T8993G mutant loads. Real-time ARMS qPCR testing showed that two brothers with features of NARP and LS had high mutant loads (>90%) in all tissues tested, similar to previously reported cases. Their sister, who has mild speech delay but attends normal school, was found to have a relatively high mutant load (mean 93%) in tissues derived from endoderm (buccal mucosa) and mesoderm (blood and skin fibroblasts). However, in tissue derived from ectoderm (hair bulbs), she carried a considerably lower proportion of mutant mtDNA. Because both surface ectoderm, which gives rise to outer epithelia and hair, and neuroectoderm, which gives rise to the central nervous system, are derived from ectoderm, it is tempting to speculate that the mutant load detected in the oligosymptomatic sister's hair bulbs is a reflection of the brain mutant load. We conclude that significant variation in tissue mutant load may occur in at least some individuals that harbor the T8993G mutation. This adds additional complexity to genetic counseling and prenatal diagnosis in such instances. Given the shared embryonic origin of hair bulbs and brain, we recommend performing hair bulb mtDNA analysis in asymptomatic or oligosymptomatic individuals that have high blood mutant loads in order to understand better the genotype-phenotype correlations related to the T8993G mutation. Relationship of primary mitochondrial respiratory chain dysfunction to fiber type abnormalities in skeletal muscle CLINICAL GENETICS Enns, G. M., Hoppel, C. L., DeArmond, S. J., Schelley, S., Bass, N., Weisiger, K., Horoupian, D., Packman, S. 2005; 68 (4): 337-348 Variation in the size and relative proportion of type 1 and type 2 muscle fibers can occur in a number of conditions, including structural myopathies, neuropathies, and various syndromes. In most cases, the pathogenesis of such fiber type changes is unknown and the etiology is heterogeneous. Skeletal muscle mitochondrial respiratory chain analysis was performed in 10 children aged 3 weeks to 5 years with abnormalities in muscle fiber type, size, and proportion. Five children were classified as having definite, four as probable, and one as possible mitochondrial disease. Type 1 fiber predominance was the most common histological finding (six of 10). On light microscopy, four cases had subtle concomitants of a mitochondriopathy, including mildly increased glycogen, lipid, and/or succinate dehydrogenase staining, and one case had more prominent evidence of underlying mitochondrial disease with marked subsarcolemmal staining. Most cases (nine of 10) had abnormal mitochondrial morphology on electron microscopy. All were found to have mitochondrial electron transport chain (ETC) abnormalities and met diagnostic criteria for mitochondrial disease. We did not ascertain any patients who had isolated fiber type abnormalities and normal respiratory chain analysis during the period of study. We conclude that mitochondrial ETC disorders may represent an etiology of at least a subset of muscle fiber type abnormalities. To establish an etiologic diagnosis and to determine the frequency of such changes in mitochondrial disease, we suggest analysis of ETC function in individuals with fiber type changes in skeletal muscle, even in the absence of light histological features suggestive of mitochondrial disorders. View details for DOI 10.1111/j.1399-0004.2005.00499.x The contribution of mitochondria to common disorders MOLECULAR GENETICS AND METABOLISM Enns, G. M. 2003; 80 (1-2): 11-26 Mitochondrial dysfunction secondary to mitochondrial and nuclear DNA mutations has been associated with energy deficiency in multiple organ systems and a variety of severe, often fatal, clinical syndromes. Although the production of energy is indeed the primary function of mitochondria, attention has also been directed toward their role producing reactive oxygen and nitrogen species and the subsequent widespread deleterious effects of these intermediates. The generation of toxic reactive intermediates has been implicated in a number of relatively common disorders, including neurodegenerative diseases, diabetes, and cancer. Understanding the role mitochondrial dysfunction plays in the pathogenesis of common disorders has provided unique insights into a number of diseases and offers hope for potential new therapies. Mitochondrial respiratory chain complex I deficiency with clinical and biochemical features of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency JOURNAL OF PEDIATRICS Enns, G. M., Bennett, M. J., Hoppel, C. L., Goodman, S. I., Weisiger, K., Ohnstad, C., Golabi, M., Packman, S. 2000; 136 (2): 251-254 The mitochondrial respiratory chain and the fatty acid oxidation cycle are theoretically interdependent on each other for normal function. We describe a patient with complex I deficiency who had clinical and biochemical features of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency including liver failure, cardiomyopathy, and consistent urine organic acid pattern. Patients with features of either a respiratory chain or fatty acid oxidation disorder should have the defect characterized biochemically because of the implications with respect to potential therapy and genetic counseling. STANDARDIZING METABOLIC DISEASE GENE AND VARIANT CURATION: THE CLINGEN INBORN ERRORS OF METABOLISM WORKING GROUP Zastrow, D., Baudet, H., Thomas, A., Shen, W., Si, C., Weaver, M., Liu, J., Goldstein, J., Thaxton, C., Ross, J., Crowley, S., Kurtz, C., McGlaughon, J., Seifert, B., Udani, R., Wallace, K., Enns, G., Feigenbaum, A., Lichter-Konecki, U., Lyon, E., Pasquali, M., Blau, N., Bali, D., Caganna, M., Hegde, M., Mooney, S., Senol, O., Watson, M., Rehder, C., Steiner, R., Craigen, W., Mao, R. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 33640 Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium. Translational science of rare diseases Ah Mew, N., Cnaan, A., McCarter, R., Choi, H., Glass, P., Rice, K., Scavo, L., Gillespie, C. W., Diaz, G. A., Berry, G. T., Wong, D., Konczal, L., McCandless, S. E., Coughlin Ii, C. R., Weisfeld-Adams, J. D., Ficicioglu, C., Yudkoff, M., Enns, G. M., Lichter-Konecki, U., Gallagher, R., Tuchman, M. 2018; 3 (3-4): 15770 Organic acidemias and urea cycle disorders are ultra-rare inborn errors of metabolism characterized by episodic acute decompensation, often associated with hyperammonemia, resulting in brain edema and encephalopathy. Retrospective reports and translational studies suggest that N-carbamylglutamate (NCG) may be effective in reducing ammonia levels during acute decompensation in two organic acidemias, propionic and methylmalonic acidemia (PA and MMA), and in two urea cycle disorders, carbamylphosphate synthetase 1 and ornithine transcarbamylase deficiency (CPSD and OTCD). We established the 9-site N-carbamylglutamate Consortium (NCGC) in order to conduct two randomized double-blind, placebo-controlled trials of NCG in acute hyperammonemia of PA, MMA, CPSD and OTCD. Conducting clinical trials is challenging in any disease, but poses unique barriers and risks in the ultra-rare disorders. As the number of clinical trials in orphan diseases increases, evaluating the successes and opportunities for improvement in such trials is essential. We summarize herein the design, methods, experiences, challenges and lessons from the NCGC-conducted trials. View details for DOI 10.3233/TRD-180031 FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia. JCI insight Manoli, I., Sysol, J. R., Epping, M. W., Li, L., Wang, C., Sloan, J. L., Pass, A., Gagne, J., Ktena, Y. P., Li, L., Trivedi, N. S., Ouattara, B., Zerfas, P. M., Hoffmann, V., Abu-Asab, M., Tsokos, M. G., Kleiner, D. E., Garone, C., Cusmano-Ozog, K., Enns, G. M., Vernon, H. J., Andersson, H. C., Grunewald, S., Elkahloun, A. G., Girard, C. L., Schnermann, J., DiMauro, S., Andres-Mateos, E., Vandenberghe, L. H., Chandler, R. J., Venditti, C. P. 2018; 3 (23) Methylmalonic acidemia (MMA), an organic acidemia characterized by metabolic instability and multiorgan complications, is most frequently caused by mutations in methylmalonyl-CoA mutase (MUT). To define the metabolic adaptations in MMA in acute and chronic settings, we studied a mouse model generated by transgenic expression of Mut in the muscle. Mut-/-;TgINS-MCK-Mut mice accurately replicate the hepatorenal mitochondriopathy and growth failure seen in severely affected patients and were used to characterize the response to fasting. The hepatic transcriptome in MMA mice was characterized by the chronic activation of stress-related pathways and an aberrant fasting response when compared with controls. A key metabolic regulator, Fgf21, emerged as a significantly dysregulated transcript in mice and was subsequently studied in a large patient cohort. The concentration of plasma FGF21 in MMA patients correlated with disease subtype, growth indices, and markers of mitochondrial dysfunction but was not affected by renal disease. Restoration of liver Mut activity, by transgenesis and liver-directed gene therapy in mice or liver transplantation in patients, drastically reduced plasma FGF21 and was associated with improved outcomes. Our studies identify mitocellular hormesis as a hepatic adaptation to metabolic stress in MMA and define FGF21 as a highly predictive disease biomarker. Elevated methylmalonic acidemia (MMA) screening markers in Hispanic and preterm newborns. Molecular genetics and metabolism Peng, G., de Fontnouvelle, C. A., Enns, G. M., Cowan, T. M., Zhao, H., Scharfe, C. 2018 Analysis of California newborn screening (NBS) data revealed a high prevalence of Hispanic infants testing positive for methylmalonic acidemia (MMA), a trend seen for both true- and false-positive cases. Here we show that Hispanic infants have significantly higher levels of MMA screening markers than non-Hispanics. Preterm birth and increased birth weight were found to be associated with elevated MMA marker levels but could not entirely explain these differences. While the preterm birth rate was higher in Blacks than Hispanics, Black infants had on average the lowest MMA marker levels. Preterm birth was associated with lower birth weight and increased MMA marker levels suggesting that gestational age is the stronger predictive covariate compared to birth weight. These findings could help explain why MMA false-positive results are more likely in Hispanic than in Black infants, which could inform screening and diagnostic procedures for MMA and potentially other disorders in newborns. Unique aspects of sequence variant interpretation for inborn errors of metabolism (IEM): The ClinGen IEM Working Group and the Phenylalanine Hydroxylase Gene. Human mutation Zastrow, D. B., Baudet, H., Shen, W., Thomas, A., Si, Y., Weaver, M. A., Lager, A. M., Liu, J., Mangels, R., Dwight, S. S., Wright, M. W., Dobrowolski, S. F., Eilbeck, K., Enns, G. M., Feigenbaum, A., Lichter-Konecki, U., Lyon, E., Pasquali, M., Watson, M., Blau, N., Steiner, R. D., Craigen, W. J., Mao, R., ClinGen Inborn Errors of Metabolism Working Group 2018; 39 (11): 156980 The ClinGen Inborn Errors of Metabolism Working Group was tasked with creating a comprehensive, standardized knowledge base of genes and variants for metabolic diseases. Phenylalanine hydroxylase (PAH) deficiency was chosen to pilot development of the Working Group's standards and guidelines. A PAH variant curation expert panel (VCEP) was created to facilitate this process. Following ACMG-AMP variant interpretation guidelines, we present the development of these standards in the context of PAH variant curation and interpretation. Existing ACMG-AMP rules were adjusted based on disease (6) or strength (5) or both (2). Disease adjustments include allele frequency thresholds, functional assay thresholds, and phenotype-specific guidelines. Our validation of PAH-specific variant interpretation guidelines is presented using 85 variants. The PAH VCEP interpretations were concordant with existing interpretations in ClinVar for 69 variants (81%). Development of biocurator tools and standards are also described. Using the PAH-specific ACMG-AMP guidelines, 714 PAH variants have been curated and will be submitted to ClinVar. We also discuss strategies and challenges in applying ACMG-AMP guidelines to autosomal recessive metabolic disease, and the curation of variants in these genes. Combining newborn metabolic and DNA analysis for second-tier testing of methylmalonic acidemia. Genetics in medicine : official journal of the American College of Medical Genetics Peng, G., Shen, P., Gandotra, N., Le, A., Fung, E., Jelliffe-Pawlowski, L., Davis, R. W., Enns, G. M., Zhao, H., Cowan, T. M., Scharfe, C. 2018 PURPOSE: Improved second-tier tools are needed to reduce false-positive outcomes in newborn screening (NBS) for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP).METHODS: We designed an assay for multiplex sequencing of 72 metabolic genes (RUSPseq) from newborn dried blood spots. Analytical and clinical performance was evaluated in 60 screen-positive newborns for methylmalonic acidemia (MMA) reported by the California Department of Public Health NBS program. Additionally, we trained a Random Forest machine learning classifier on NBS data to improve prediction of true and false-positive MMA cases.RESULTS: Of 28 MMA patients sequenced, we found two pathogenic or likely pathogenic (P/LP) variants in a MMA-related gene in 24 patients, and one pathogenic variant and a variant of unknown significance (VUS) in 1 patient. No such variant combinations were detected in MMA false positives and healthy controls. Random Forest-based analysis of the entire NBS metabolic profile correctly identified the MMA patients and reduced MMA false-positive cases by 51%. MMA screen-positive newborns were more likely of Hispanic ethnicity.CONCLUSION: Our two-pronged approach reduced false positives by half and provided a reportable molecular finding for 89% of MMA patients. Challenges remain in newborn metabolic screening and DNA variant interpretation in diverse multiethnic populations. Current clinical evidence does not support a link between TBL1XR1 and Rett syndrome: Description of one patient with Rett features and a novel mutation in TBL1XR1, and a review of TBL1XR1 phenotypes AMERICAN JOURNAL OF MEDICAL GENETICS PART A Zaghlula, M., Glaze, D. G., Enns, G. M., Potocki, L., Schwabe, A. L., Suter, B. 2018; 176 (7): 168387 Mitochondrial disease phenotypes of 999 patients in the North American Mitochondrial Disease Consortium (NAMDC) Barca, E., Cooley, V., Schoenaker, R., Emmanuele, V., DiMauro, S., Cohen, B., Karaa, A., Vladutiu, G., Haas, R., Haas, R., Van Hove, J., Scaglia, F., Parikh, S., Bedoyan, J., DeBrosse, S., Gavrilova, R., Saneto, R., Enns, G., Stacpoole, P., Ganesh, J., Larson, A., Zolkipli-Cunningham, Z., Falk, M., Goldstein, A., Tarnopolsky, M., Camp, K., Krotoski, D., Engelstad, K., Rosales, X., Kriger, J., Buchsbaum, R., Thompson, J., Hirano, M. LIPPINCOTT WILLIAMS & WILKINS. 2018 PERSPECTIVES ON UREA CYCLE DISORDER MANAGEMENT: RESULTS OF A CLINICIAN SURVEY Burdett, A., Francis-Sedlak, M., Vockley, J., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2018: 22122 Prenatal treatment of ornithine transcarbamylase deficiency. Molecular genetics and metabolism Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., Lyell, D. J., Esquivel, C. O., Homeyer, M., Hudgins, L., Hurwitz, M., Palma, J. P., Schelley, S., Akula, V. P., Summar, M. L., Enns, G. M. 2018 Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor.Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery.Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years.Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome. Triheptanoin: A Rescue Therapy for Cardiogenic Shock in Carnitine-acylcarnitine Translocase Deficiency. JIMD reports Mahapatra, S., Ananth, A., Baugh, N., Damian, M., Enns, G. M. 2018; 39: 1923 Carnitine-acylcarnitine translocase (CACT) deficiency is a rare long-chain fatty acid oxidation disorder (LC-FAOD) with high mortality due to cardiomyopathy or lethal arrhythmia. Triheptanoin (UX007), an investigational drug composed of synthetic medium odd-chain triglycerides, is a novel therapy in development for LC-FAOD patients. However, cases of its safe and efficacious use to reverse severe heart failure in CACT deficiency are limited. Here, we present a detailed report of an infant with CACT deficiency admitted in metabolic crisis that progressed into severe cardiogenic shock who was successfully treated by triheptanoin. The child was managed, thereafter, on triheptanoin until her death at 3 years of age from a cardiopulmonary arrest in the setting of acute respiratory illness superimposed on chronic hypercarbic respiratory failure. A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network. The Journal of pediatrics Reuter, C. M., Brimble, E., DeFilippo, C., Dries, A. M., Enns, G. M., Ashley, E. A., Bernstein, J. A., Fisher, P. G., Wheeler, M. T. 2018 Management of ophthalmologic manifestations of mitochondrial diseases Response GENETICS IN MEDICINE Parikh, S., Goldstein, A., Karaa, A., Koenig, M., Anselm, I., Brunel-Guitton, C., Christodoulou, J., Cohen, B. H., Dimmock, D., Enns, G. M., Falk, M. J., Feigenbaum, A., Frye, R. E., Ganesh, J., Griesemer, D., Haas, R., Horvath, R., Korson, M., Kruer, M. C., Mancuso, M., McCormack, S., Raboisson, M., Reimschisel, T., Salvarinova, R., Saneto, R. P., Scaglia, F., Shoffner, J., Stacpoole, P. W., Sue, C. M., Tarnopolsky, M., Van Karnebeek, C., Wolfe, L. A., Cunningham, Z., Rahman, S., Chinnery, P. F. 2017; 19 (12) Correction of hyperleucinemia in MSUD patients on leucine-free dietary therapy. Molecular genetics and metabolism Scott, A. I., Cusmano-Ozog, K., Enns, G. M., Cowan, T. M. 2017 PURPOSE: Maple Syrup Urine Disease (MSUD) is a rare disorder of branched-chain amino acid catabolism associated with encephalopathy from accumulation of leucine. Leucine is closely monitored during normal growth and particularly during acute illness. As most hospitals do not have access to rapid plasma amino acid quantification, the initial management is often empirical. A model describing the reduction of plasma leucine in hyperleucinemic patients on leucine-free formula would help to guide management and optimize testing frequency.METHODS: We retrospectively reviewed charts from 15 MSUD patients comprising 29 episodes of hyperleucinemia that were managed with leucine-free formula. Episodes were categorized by clinical presentation.RESULTS: Upon leucine restriction, plasma leucine concentrations fell exponentially at a rate proportional to approximately 50% of the starting value over each 24-hour period. Recovery appears to be sensitive to clinical status and triggering event of the hyperleucinemic episode. Patients with upper respiratory infections generally recovered slowly, while cases of dietary non-adherence resolved more quickly.CONCLUSION: This general model may help anticipate leucine levels during clinical management of MSUD patients when using nutritional support and leucine-free formula. The response of individual patients may vary depending on clinical status and triggering factors. Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature. journal of pediatrics Sylvester, K. G., Kastenberg, Z. J., Moss, R. L., Enns, G. M., Cowan, T. M., Shaw, G. M., Stevenson, D. K., Sinclair, T. J., Scharfe, C., Ryckman, K. K., Jelliffe-Pawlowski, L. L. 2017; 181: 80-85 e1 To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm.A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009.Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC. Each log unit increase in C5 and free carnitine /(C16+18:1) was associated with a 78% and a 76% increased risk for developing NEC, respectively (OR 1.78, 95% CI 1.53-2.02, and OR 1.76, 95% CI 1.51-2.06). Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified 89.8% of newborns with NEC in the model-development cohort (area under the curve0.898, 95% CI 0.889-0.907) and 90.8% of the newborns with NEC in the validation cohort (area under the curve0.908, 95% CI 0.901-0.930).Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies. Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria JOURNAL OF INHERITED METABOLIC DISEASE Olahova, M., Thompson, K., Hardy, S. A., Barbosa, I. A., Besse, A., Anagnostou, M., White, K., Davey, T., Simpson, M. A., Champion, M., Enns, G., Schelley, S., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M., McFarland, R., Deshpande, C., Bonnen, P. E., Taylor, R. W. 2017; 40 (1): 121-130 View details for DOI 10.1007/s10545-016-9977-2 Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Parikh, S., Goldstein, A., Karaa, A., Koenig, M. K., Anselm, I., Brunel-Guitton, C., Christodoulou, J., Cohen, B. H., Dimmock, D., Enns, G. M., Falk, M. J., Feigenbaum, A., Frye, R. E., Ganesh, J., Griesemer, D., Haas, R., Horvath, R., Korson, M., Kruer, M. C., Mancuso, M., McCormack, S., Raboisson, M. J., Reimschisel, T., Salvarinova, R., Saneto, R. P., Scaglia, F., Shoffner, J., Stacpoole, P. W., Sue, C. M., Tarnopolsky, M., Van Karnebeek, C., Wolfe, L. A., Cunningham, Z. Z., Rahman, S., Chinnery, P. F. 2017 The purpose of this statement is to provide consensus-based recommendations for optimal management and care for patients with primary mitochondrial disease. This statement is intended for physicians who are engaged in the diagnosis and management of these patients. Working group members were appointed by the Mitochondrial Medicine Society. The panel included members with several different areas of expertise. The panel members utilized surveys and the Delphi method to reach consensus. We anticipate that this statement will need to be updated as the field continues to evolve. Consensus-based recommendations are provided for the routine care and management of patients with primary genetic mitochondrial disease. De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. American journal of human genetics Kry, S., van Woerden, G. M., Besnard, T., Proietti Onori, M., Latypova, X., Towne, M. C., Cho, M. T., Prescott, T. E., Ploeg, M. A., Sanders, S., Stessman, H. A., Pujol, A., Distel, B., Robak, L. A., Bernstein, J. A., Denomm-Pichon, A. S., Lesca, G., Sellars, E. A., Berg, J., Carr, W., Busk, . L., van Bon, B. W., Waugh, J. L., Deardorff, M., Hoganson, G. E., Bosanko, K. B., Johnson, D. S., Dabir, T., Holla, . L., Sarkar, A., Tveten, K., de Bellescize, J., Braathen, G. J., Terhal, P. A., Grange, D. K., van Haeringen, A., Lam, C., Mirzaa, G., Burton, J., Bhoj, E. J., Douglas, J., Santani, A. B., Nesbitt, A. I., Helbig, K. L., Andrews, M. V., Begtrup, A., Tang, S., van Gassen, K. L., Juusola, J., Foss, K., Enns, G. M., Moog, U., Hinderhofer, K., Paramasivam, N., Lincoln, S., Kusako, B. H., Lindenbaum, P., Charpentier, E., Nowak, C. B., Cherot, E., Simonet, T., Ruivenkamp, C. A., Hahn, S., Brownstein, C. A., Xia, F., Schmitt, S., Deb, W., Bonneau, D., Nizon, M., Quinquis, D., Chelly, J., Rudolf, G., Sanlaville, D., Parent, P., Gilbert-Dussardier, B., Toutain, A., Sutton, V. R., Thies, J., Peart-Vissers, L. E., Boisseau, P., Vincent, M., Grabrucker, A. M., Dubourg, C., Tan, W. H., Verbeek, N. E., Granzow, M., Santen, G. W., Shendure, J., Isidor, B., Pasquier, L., Redon, R., Yang, Y., State, M. W., Kleefstra, T., Cogn, B., Petrovski, S., Retterer, K., Eichler, E. E., Rosenfeld, J. A., Agrawal, P. B., Bzieau, S., Odent, S., Elgersma, Y., Mercier, S. 2017; 101 (5): 76888 Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway. Nutritional interventions in primary mitochondrial disorders: Developing an evidence base. Molecular genetics and metabolism Camp, K. M., Krotoski, D., Parisi, M. A., Gwinn, K. A., Cohen, B. H., Cox, C. S., Enns, G. M., Falk, M. J., Goldstein, A. C., Gopal-Srivastava, R., Gorman, G. S., Hersh, S. P., Hirano, M., Hoffman, F. A., Karaa, A., MacLeod, E. L., McFarland, R., Mohan, C., Mulberg, A. E., Odenkirchen, J. C., Parikh, S., Rutherford, P. J., Suggs-Anderson, S. K., Tang, W. H., Vockley, J., Wolfe, L. A., Yannicelli, S., Yeske, P. E., Coates, P. M. 2016; 119 (3): 187-206 In December 2014, a workshop entitled "Nutritional Interventions in Primary Mitochondrial Disorders: Developing an Evidence Base" was convened at the NIH with the goals of exploring the use of nutritional interventions in primary mitochondrial disorders (PMD) and identifying knowledge gaps regarding their safety and efficacy; identifying research opportunities; and forging collaborations among researchers, clinicians, patient advocacy groups, and federal partners. Sponsors included the NIH, the Wellcome Trust, and the United Mitochondrial Diseases Foundation. Dietary supplements have historically been used in the management of PMD due to their potential benefits and perceived low risk, even though little evidence exists regarding their effectiveness. PMD are rare and clinically, phenotypically, and genetically heterogeneous. Thus patient recruitment for randomized controlled trials (RCTs) has proven to be challenging. Only a few RCTs examining dietary supplements, singly or in combination with other vitamins and cofactors, are reported in the literature. Regulatory issues pertaining to the use of dietary supplements as treatment modalities further complicate the research and patient access landscape. As a preface to exploring a research agenda, the workshop included presentations and discussions on what PMD are; how nutritional interventions are used in PMD; challenges and barriers to their use; new technologies and approaches to diagnosis and treatment; research opportunities and resources; and perspectives from patient advocacy, industry, and professional organizations. Seven key areas were identified during the workshop. These areas were: 1) defining the disease, 2) clinical trial design, 3) biomarker selection, 4) mechanistic approaches, 5) challenges in using dietary supplements, 6) standards of clinical care, and 7) collaboration issues. Short- and long-term goals within each of these areas were identified. An example of an overarching goal is the enrollment of all individuals with PMD in a natural history study and a patient registry to enhance research capability. The workshop demonstrates an effective model for fostering and enhancing collaborations among NIH and basic research, clinical, patient, pharmaceutical industry, and regulatory stakeholders in the mitochondrial disease community to address research challenges on the use of dietary supplements in PMD. Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine. Journal of inherited metabolic disease Gomez-Ospina, N., Scott, A. I., Oh, G. J., Potter, D., Goel, V. V., Destino, L., Baugh, N., Enns, G. M., Niemi, A., Cowan, T. M. 2016; 39 (6): 821-829 Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can aid in identifying this condition, although their relationship to the clinical manifestations is not known. Herein we describe clinical and laboratory findings in two fraternal twins with hawkinsinuria who presented with failure to thrive and metabolic acidosis. Close clinical follow-up and laboratory testing revealed previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia, and anemia, along with the characteristic urinary metabolites, including massive pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal growth and normalized or improved most biochemical parameters. The dramatic response to NAC therapy supports the idea that glutathione depletion plays a key role in the pathogenesis of hawkinsinuria. Triheptanoin treatment in patients with pediatric cardiomyopathy associated with long chain-fatty acid oxidation disorders. Molecular genetics and metabolism Vockley, J., Charrow, J., Ganesh, J., Eswara, M., DIAZ, G. A., McCracken, E., Conway, R., Enns, G. M., Starr, J., Wang, R., Abdenur, J. E., Sanchez-de-Toledo, J., Marsden, D. L. 2016; 119 (3): 223-231 Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy was treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12-45%. Improvements in EF began between 2 and 21days following initiation of triheptanoin, and peaked at 33-71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD. De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms AMERICAN JOURNAL OF HUMAN GENETICS Weiss, K., Terhal, P. A., Cohen, L., Bruccoleri, M., Irving, M., Martinez, A. F., Rosenfeld, J. A., Machol, K., Yang, Y., Liu, P., Walkiewicz, M., Beuten, J., Gomez-Ospina, N., Haude, K., Fong, C., Enns, G. M., Bernstein, J. A., Fan, J., Gotway, G., Ghorbani, M., van Gassen, K., Monroe, G. R., van Haaften, G., Basel-Vanagaite, L., Yang, X., Campeau, P. M., Muenke, M. 2016; 99 (4): 934-941 Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the roleof CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. View details for DOI 10.1016/j.ajhg.2016.08.001 Impaired Health-Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia. Journal of genetic counseling Splinter, K., Niemi, A., Cox, R., Platt, J., Shah, M., Enns, G. M., Kasahara, M., Bernstein, J. A. 2016; 25 (5): 936-944 An understanding of health related quality of life (HRQoL) in children and families affected by methylmalonic acidemia (MMA) is important in planning counseling and therapeutic intervention. Liver transplantation (LT) is used as a treatment for MMA; however, its risks and benefits continue to be investigated. The purpose of this study was twofold: (1) to measure HRQoL in children and families affected by MMA using the Pediatric Quality of Life Inventory (PedsQL) parent version, and (2) to assess the impact of LT on HRQoL by comparing LT and non-LT patient scores and free responses. Parents/caregivers reported lower scores on the majority of the PedsQL scales as compared to samples of healthy children, children with solid organ transplants for indications other than MMA, and families affected by chronic conditions. Scores for children with MMA were lowest in school and social functioning and scores for families were lowest in worry and activity impairment. There were no significant differences in LT and non-LT patient scores on the PedsQL scales. Our results document the negative impact of MMA on HRQoL. View details for DOI 10.1007/s10897-015-9921-x Living donor liver transplantation for inborn errors of metabolism - An underutilized resource in the United States. Pediatric transplantation Pham, T. A., Enns, G. M., Esquivel, C. O. 2016; 20 (6): 770-773 Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver. View details for DOI 10.1111/petr.12746 The M405V allele of the glutaryl-CoA dehydrogenase gene is an important marker for glutaric aciduria type I (GA-I) low excretors. Molecular genetics and metabolism Schillaci, L. P., Greene, C. L., Strovel, E., Rispoli-Joines, J., Spector, E., Woontner, M., Scharer, G., Enns, G. M., Gallagher, R., Zinn, A. B., McCandless, S. E., Hoppel, C. L., Goodman, S. I., Bedoyan, J. K. 2016; 119 (1-2): 50-56 Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria resulting from a functional deficiency of glutaryl-CoA dehydrogenase, encoded by GCDH. Two clinically indistinguishable diagnostic subgroups of GA-I are known; low and high excretors (LEs and HEs, respectively). Early medical and dietary interventions can result in significantly better outcomes and improved quality of life for patients with GA-I. We report on nine cases of GA-I LE patients all sharing the M405V allele with two cases missed by newborn screening (NBS) using tandem mass spectrometry (MS/MS). We describe a novel case with the known pathogenic M405V variant and a novel V133L variant, and present updated and previously unreported clinical, biochemical, functional and molecular data on eight other patients all sharing the M405V allele. Three of the nine patients are of African American ancestry, with two as siblings. GCDH activity was assayed in six of the nine patients and varied from 4 to 25% of the control mean. We support the use of urine glutarylcarnitine as a biochemical marker of GA-I by demonstrating that glutarylcarnitine is efficiently cleared by the kidney (50-90%) and that plasma and urine glutarylcarnitine follow a linear relationship. We report the allele frequencies for three known GA-I LE GCDH variants (M405V, V400M and R227P) and note that both the M405V and V400M variants are significantly more common in the population of African ancestry compared to the general population. This report highlights the M405V allele as another important molecular marker in patients with the GA-I LE phenotype. Therefore, the incorporation into newborn screening of molecular screening for the M405V and V400M variants in conjunction with MS/MS could help identify asymptomatic at-risk GA-I LE patients that could potentially be missed by current NBS programs. Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period. Journal of ultrasound in medicine Blumenfeld, Y. J., Davis, A. S., Hintz, S. R., Milan, K., Messner, A. H., Barth, R. A., Hudgins, L., Chueh, J., Homeyer, M., Bernstein, J. A., Enns, G., Atwal, P., Manning, M. 2016; 35 (6): 1353-1358 Binder phenotype, or maxillonasal dysostosis, is a distinctive pattern of facial development characterized by a short nose with a flat nasal bridge, an acute nasolabial angle, a short columella, a convex upper lip, and class III malocclusion. We report 3 cases of prenatally diagnosed Binder phenotype associated with perinatal respiratory impairment. View details for DOI 10.7863/ultra.15.02050 Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder PEDIATRIC NEUROLOGY Ananth, A. L., Robichaux-Viehoever, A., Kim, Y., Hanson-Kahn, A., Cox, R., Enns, G. M., Strober, J., Willing, M., Schlaggar, B. L., Wu, Y. W., Bernstein, J. A. 2016; 59: 81-84 Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novoGNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy.Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients.All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age fouryears in all but one patient, who developed chorea at 14years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients.Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy. View details for DOI 10.1016/j.pediatrneurol.2016.02.018 Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures AMERICAN JOURNAL OF HUMAN GENETICS Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., Wadley, A., Politi, A. R., Colombo, S., Zhu, X., Ren, Z., Andrews, I., Dudding-Byth, T., Schneider, A. L., Wallace, G., Rosen, A. B., Schelley, S., Enns, G. M., Corre, P., Dalton, J., Mercier, S., Latypova, X., Schmitt, S., Guzman, E., Moore, C., Bier, L., Heinzen, E. L., Karachunski, P., Shur, N., Grebe, T., Basinger, A., Nguyen, J. M., Bezieau, S., Wierenga, K., Bernstein, J. A., Scheffer, I. E., Rosenfeld, J. A., Mefford, H. C., Isidor, B., Goldstein, D. B. 2016; 98 (5): 1001-1010 Whole-exome sequencing of 13 individuals with developmental delay commonly accompanied by abnormal muscle tone and seizures identified de novo missense mutations enriched within a sub-region of GNB1, a gene encoding the guanine nucleotide-binding proteinsubunit beta-1, G. These 13 individuals were identified among a base of 5,855 individuals recruited for various undiagnosed genetic disorders. The probability of observing 13 or more de novo mutations by chance among 5,855 individuals is very low (p=7.1 10(-21)), implicating GNB1 as a genome-wide-significant disease-associated gene. The majority of these 13 mutations affect known G binding sites, which suggests that a likely disease mechanism is through the disruption of the protein interface required for G-G interaction (resulting in a constitutively active G) or through the disruption of residues relevant for interaction between G and certain downstream effectors (resulting in reduced interaction with the effectors). Strikingly, 8 of the 13 individuals recruited here for a neurodevelopmental disorder have a germline de novo GNB1 mutation that overlaps a set of five recurrent somatic tumor mutations for which recent functional studies demonstrated a gain-of-function effect due to constitutive activation of G protein downstream signaling cascades for some of the affected residues. Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants GENETICS IN MEDICINE Jones, S. A., Valayannopoulos, V., Schneider, E., Eckert, S., Banikazemi, M., Bialer, M., Cederbaum, S., Chan, A., Dhawan, A., Di Rocco, M., Domm, J., Enns, G. M., Finegold, D., Gargus, J. J., Guardamagna, O., Hendriksz, C., Mahmoud, I. G., Raiman, J., Selim, L. A., Whitley, C. B., Zaki, O., Quinn, A. G. 2016; 18 (5): 452-458 The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients.Records for 35 patients, 26 with early GF, were analyzed. Prominent symptom manifestations included vomiting, diarrhea, and steatorrhea. Median age at death was 3.7 months; estimated probability of survival past age 12 months was 0.114 (95% confidence interval (CI): 0.009-0.220). Among patients with early GF, median age at death was 3.5 months; estimated probability of survival past age 12 months was 0.038 (95% CI: 0.000-0.112). Treated patients (hematopoietic stem cell transplant (HSCT), n = 9; HSCT and liver transplant, n = 1) in the overall population and the early GF subset survived longer than untreated patients, but survival was still poor (median age at death, 8.6 months).These data confirm and expand earlier insights on the progression and course of LALD presenting in infancy. Despite variations in the nature, onset, and severity of clinical manifestations, and treatment attempts, clinical outcome was poor.Genet Med 18 5, 452-458. Line intensities and temperature-dependent line broadening coefficients of Q-branch transitions in the v(2) band of ammonia near 10.4 mu m JOURNAL OF QUANTITATIVE SPECTROSCOPY & RADIATIVE TRANSFER Sur, R., Spearrin, R. M., Peng, W. Y., Strand, C. L., Jeffries, J. B., Enns, G. M., Hanson, R. K. 2016; 175: 90-99 View details for DOI 10.1016/j.jqsrt.2016.02.002 RATE OF LEUCINE CLEARANCE IN MSUD Scott, A. I., Cusmano-Ozog, K., Enns, G. M., Cowan, T. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2016: 284 Clinical Features of Lysosomal Acid Lipase Deficiency. Journal of pediatric gastroenterology and nutrition Burton, B. K., Deegan, P. B., Enns, G. M., Guardamagna, O., Horslen, S., Hovingh, G. K., Lobritto, S. J., Malinova, V., Mclin, V. A., Raiman, J., Di Rocco, M., Santra, S., Sharma, R., Sykut-Cegielska, J., Whitley, C. B., Eckert, S., Valayannopoulos, V., Quinn, A. G. 2015; 61 (6): 619-625 The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults.Investigators reviewed medical records of LAL D patients ages 5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset.A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n=31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was 1.15 multiples of normal (MN) and median spleen volume was 2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years).This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation. View details for DOI 10.1097/MPG.0000000000000935 Reply. journal of pediatrics Niemi, A., Enns, G. M. 2015; 167 (5): 1173-1174 De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay. Cold Spring Harbor molecular case studies Yang, H., Douglas, G., Monaghan, K. G., Retterer, K., Cho, M. T., Escobar, L. F., Tucker, M. E., Stoler, J., Rodan, L. H., Stein, D., Marks, W., Enns, G. M., Platt, J., Cox, R., Wheeler, P. G., Crain, C., Calhoun, A., Tryon, R., Richard, G., Vitazka, P., Chung, W. K. 2015; 1 (1) Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors. Additional common clinical features include dysmorphic facial features and feeding difficulties associated with failure to thrive and short stature. The AHDC1 gene has only one coding exon, and the protein contains conserved regions including AT-hook motifs and a PDZ binding domain. We postulate that all seven variants detected in these patients result in a truncated protein missing critical functional domains, disrupting interactions with other proteins important for brain development. Our study demonstrates that truncating variants in AHDC1 are associated with ID and are primarily associated with a neurodevelopmental phenotype. View details for DOI 10.1101/mcs.a000562 A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts. Glycobiology He, P., Grotzke, J. E., Ng, B. G., Gunel, M., Jafar-Nejad, H., Cresswell, P., Enns, G. M., Freeze, H. H. 2015; 25 (8): 836-844 N-Glycanase 1, encoded by NGLY1, catalyzes the deglycosylation of misfolded N-linked glycoproteins retrotranslocated into the cytosol. We identified nine cases with mutations in NGLY1. The patients show developmental delay, seizures, peripheral neuropathy, abnormal liver function and alacrima (absence of tears). The mutations in NGLY1 resulted in the absence of N-glycanase 1 protein in patient-derived fibroblasts. Applying a recently established cellular deglycosylation-dependent Venus fluorescence assay, we found that patient fibroblasts had dramatically reduced fluorescence, indicating a pronounced reduction in N-glycanase enzymatic activity. Using this assay, we could find no evidence of other related activities. Our findings reveal that NGLY1 mutations destroy both N-glycanase 1 protein and enzymatic activity. View details for DOI 10.1093/glycob/cwv024 ClinGen - The Clinical Genome Resource NEW ENGLAND JOURNAL OF MEDICINE Rehm, H. L., Berg, J. S., Brooks, L. D., Bustamante, C. D., Evans, J. P., Landrum, M. J., Ledbetter, D. H., Maglott, D. R., Martin, C. L., Nussbaum, R. L., Plon, S. E., Ramos, E. M., Sherry, S. T., Watson, M. S. 2015; 372 (23): 2235-2242 View details for DOI 10.1056/NEJMsr1406261 Treatment of Methylmalonic Acidemia by Liver or Combined Liver-Kidney Transplantation JOURNAL OF PEDIATRICS Niemi, A., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., Bonham, C. A., Concepcion, W., Esquivel, C. O., Enns, G. M. 2015; 166 (6): 1455-? Correlation of HMPAO uptake with live single cell synchrotron mid-Infrared spectromicroscopy in inherited mitochondrial disease Holman, E., Chen, L., Holman, H., Enns, G., Blankenberg, F. SOC NUCLEAR MEDICINE INC. 2015 Long-term safety and efficacy of sapropterin: The PKUDOS registry experience MOLECULAR GENETICS AND METABOLISM Longo, N., Arnold, G. L., Pridjian, G., Enns, G. M., Ficicioglu, C., Parker, S., Cohen-Pfeffer, J. L. 2015; 114 (4): 557-563 The Phenylketonuria (PKU) Demographics, Outcomes and Safety (PKUDOS) registry is designed to provide longitudinal safety and efficacy data on subjects with PKU who are (or have been) treated with sapropterin dihydrochloride. The PKUDOS population consists of 1189 subjects with PKU: N = 504 who were continuously exposed to sapropterin from date of registry enrollment, N = 211 who had intermittent exposure to the drug, and N = 474 with some other duration of exposure. Subjects continuously exposed to sapropterin showed an average 34% decrease in blood phenylalanine (Phe)--from 591 382 mol/L at baseline to 392 239 mol/L (p = 0.0009) after 5 years. This drop in blood Phe was associated with an increase in dietary Phe tolerance [from 1000 959 mg/day (pre-sapropterin baseline) to 1539 840 mg/day after 6 years]. Drug-related adverse events (AEs) were reported in 6% of subjects, were mostly considered non-serious, and were identified in the gastrointestinal, respiratory, and nervous systems. Serious drug-related AEs were reported in 1% of subjects. Similar safety and efficacy data were observed for children<4 years. Long-term data from the PKUDOS registry suggest that sapropterin has a tolerable safety profile and that continuous use is associated with a significant and persistent decrease in blood Phe and improvements in dietary Phe tolerance. Identification of HIBCH Gene Mutations Causing Autosomal Recessive Leigh Syndrome: A Gene Involved in Valine Metabolism PEDIATRIC NEUROLOGY Soler-Alfonso, C., Enns, G. M., Koenig, M. K., Saavedra, H., Bonfante-Mejia, E., Northrup, H. 2015; 52 (3): 361-365 Leigh syndrome is a progressive neurodegenerative disorder with usual onset of symptoms during the first year of life. The disorder has been associated with mutations in over 30 genes. This difficulty with genetic heterogeneity makes whole exome sequencing a more cost-effective approach for investigation of etiology.We describe an individual with typical Leigh syndrome who was found to have compound heterozygous mutations in the gene HIBCH (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism of valine. She exhibited significant clinical improvement after a valine-restricted diet.A subset of patients with uncharacterized Leigh syndrome present with specific biochemical abnormalities. This report highpoints the challenges and restrictions of routine metabolic testing and features the recognition of inborn errors of metabolism as potential treatable causes of Leigh syndrome. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency JOURNAL OF HEPATOLOGY Valayannopoulos, V., Malinova, V., Honzik, T., Balwani, M., Breen, C., Deegan, P. B., Enns, G. M., Jones, S. A., Kane, J. P., Stock, E. O., Tripuraneni, R., Eckert, S., Schneider, E., Hamilton, G., Middleton, M. S., Sirlin, C., Kessler, B., Bourdon, C., Boyadjiev, S. A., Sharma, R., Twelves, C., Whitley, C. B., Quinn, A. G. 2014; 61 (5): 1135-1142 Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase.Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals.216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected.Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). View details for DOI 10.1016/j.jhep.2014.06.022 Abnormal Hepatocellular Mitochondria in Methylmalonic Acidemia ULTRASTRUCTURAL PATHOLOGY Wilnai, Y., Enns, G. M., Niemi, A., Higgins, J., Vogel, H. 2014; 38 (5): 309-314 Methylmalonic acidemia (MMA) is one of the most frequently encountered forms of branched-chain organic acidemias. Biochemical abnormalities seen in some MMA patients, such as lactic acidemia and increased tricarboxylic acid cycle intermediate excretion, suggest mitochondrial dysfunction. In order to investigate the possibility of mitochondrial involvement in MMA, we examined liver tissue for evidence of mitochondrial ultrastructural abnormalities. Five explanted livers obtained from MMA mut(0) patients undergoing liver transplantation were biopsied. All patients had previous episodes of metabolic acidosis, lactic acidemia, ketonuria, and hyperammonemia. All biopsies revealed a striking mitochondriopathy by electron microscopy. Mitochondria were markedly variable in size, shape, and conformation of cristae. The inner matrix appeared to be greatly expanded and the cristae were diminutive and disconnected. No crystalloid inclusions were noted. This series clearly documents extensive mitochondrial ultrastructure abnormalities in liver samples from MMA patients undergoing transplantation, providing pathological evidence for mitochondrial dysfunction in the pathophysiology of MMA mut(0). Considering the trend to abnormally large mitochondria, the metabolic effects of MMA may restrict mitochondrial fission or promote fusion. The correlation between mitochondrial dysfunction and morphological abnormalities in MMA may provide insights for better understanding and monitoring of optimized or novel therapeutic strategies. View details for DOI 10.3109/01913123.2014.921657 Clinical whole-exome sequencing: are we there yet? GENETICS IN MEDICINE Atwal, P. S., Brennan, M., Cox, R., Niaki, M., Platt, J., Homeyer, M., Kwan, A., Parkin, S., Schelley, S., Slattery, L., Wilnai, Y., Bernstein, J. A., Enns, G. M., Hudgins, L. 2014; 16 (9): 717-719 Background:Clinical laboratories began offering whole-exome sequencing in 2011 at a cost between $4,500 and $9,000. Reported detection rates for deleterious mutations range from 25 to 50%. Based on the experience of our clinical genetics service, actual success rates may be lower than estimated rates. We report results from our own experience along with a survey of clinical geneticists to ascertain (i) current success rates for causal gene detection in a clinical setting; (ii) if there are insurance authorization issues; and (iii) if turnaround times quoted by the clinical laboratories are accurate; we also gauge provider opinions toward clinical whole-exome sequencing.Methods:We reviewed our results and the results of a survey that was electronically distributed to 47 clinical genetics centers.Results:A total of 35 exome reports were available. If all positive results are collated, we observe a success rate of 22.8%. One result incorrectly identified a known benign variant as pathogenic. Some insurers covered all testing, whereas others denied any insurance coverage. Only three (23.1%) of our reports were available within the laboratory's quoted turnaround times. More than 50% of clinicians queried in our survey had not ordered whole-exome sequencing at the current time, many stating concerns regarding interpretation, insurance coverage, and cost.Conclusion:Clinical whole-exome sequencing has proven diagnostic utility; however, currently many clinicians have concerns regarding interpretation of results, insurance coverage, and cost.Genet Med advance online publication 13 February 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.10. Treatment of Mitochondrial Disorders: Antioxidants and Beyond JOURNAL OF CHILD NEUROLOGY Enns, G. M. 2014; 29 (9): 1235-1240 Although mitochondrial disorders are among the most common inherited conditions that cause neurologic impairment, there are currently no U.S. Food and Drug Administration (FDA)-approved medications designed to treat primary mitochondrial disease. This is in part related to the lack of biomarkers to monitor disease status or response to treatment and the paucity of randomized, controlled clinical trials focused on mitochondrial disease therapies. Despite this discouraging historical precedent, a number of new approaches to mitochondrial disease therapy are on the horizon. By studying metabolites central to redox chemistry, investigators are gaining new insights into potential noninvasive biomarkers. Controlled clinical trials designed to study the effects of novel redox-modulating therapies, such as EPI-743, in patients with inherited mitochondrial disease are also underway. Furthermore, several new compounds with potential effects on inner mitochondrial membrane function and mitochondrial biogenesis are in development. Such advances are providing the foundation for a new era in mitochondrial disease therapeutics. View details for DOI 10.1177/0883073814538509 Points to Consider in the Clinical Use of NGS Panels for Mitochondrial Disease: An Analysis of Gene Inclusion and Consent Forms JOURNAL OF GENETIC COUNSELING Platt, J., Cox, R., Enns, G. M. 2014; 23 (4): 594-603 Mitochondrial next generation sequencing (NGS) panels offer single-step analysis of the numerous nuclear genes involved in the structure, function, and maintenance of mitochondria. However, the complexities of mitochondrial biology and genetics raise points for consideration in clinical use of these tests. To understand the current status of mitochondrial genetic testing, we assessed the gene offerings and consent forms of mitochondrial NGS panels available from seven US-based clinical laboratories. The NGS panels varied markedly in number of genes (101-1204 genes), and the proportion of genes causing "classic" mitochondrial diseases and their phenocopies ranged widely between labs (18 %-94 % of panel contents). All panels included genes not associated with classic mitochondrial diseases (6 %-28 % of panel contents), including genes causing adult-onset neurodegenerative disorders, cancer predisposition, and other genetic syndromes or inborn errors of metabolism. Five of the panels included genes that are not listed in OMIM to be associated with a disease phenotype (5 %-49 % of panel contents). None of the consent documents reviewed had options for patient preference regarding receipt of incidental findings. These findings raise points of discussion applicable to mitochondrial diagnostics, but also to the larger arenas of exome and genome sequencing, including the need to consider the boundaries between clinical and research testing, the necessity of appropriate informed consent, and the responsibilities of clinical laboratories and clinicians. Based on these findings, we recommend careful evaluation by laboratories of the genes offered on NGS panels, clear communication of the predicted phenotypes, and revised consent forms to allow patients to make choices about receiving incidental findings. We hope that our analysis and recommendations will help to maximize the considerable clinical utility of NGS panels for the diagnosis of mitochondrial disease. Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway (vol 111, pg 236, 2014) GENETICS IN MEDICINE Enns, G. M., Shashi, V., Bainbridge, M., Gambello, M. J., Zahir, F. R., Bast, T., Crimian, R., Schoch, K., Platt, J., Cox, R., Bernstein, J. A., Scavina, M., Walter, R. S., Bibb, A., Jones, M., Hegde, M., Graham, B. H., Need, A. C., Oviedo, A., Schaaf, C. P., Boyle, S., Butte, A. J., Chen, R., Chen, R., Clark, M. J., Haraksingh, R., Cowan, T. M., He, P., Langlois, S., Zoghbi, H. Y., Snyder, M., Gibbs, R. A., Freeze, H. H., Goldstein, D. B., Chen, R., FORGE Canada Consortium 2014; 16 (7): 568 Monitoring mitochondrial disease related nephropathy and subclinical redox stress of the brain in the kd/kd murine model Blankenberg, F., Enns, G. SOC NUCLEAR MEDICINE INC. 2014 HMPAO uptake assay with t-BHP or irradiation of primary patient SURF-1 fibroblast cultures Holman, E., Enns, G., Blankenberg, F. SOC NUCLEAR MEDICINE INC. 2014 Clinical interpretation and implications of whole-genome sequencing. JAMA : the journal of the American Medical Association Dewey, F. E., Grove, M. E., Pan, C., Goldstein, B. A., Bernstein, J. A., Chaib, H., Merker, J. D., Goldfeder, R. L., Enns, G. M., David, S. P., Pakdaman, N., Ormond, K. E., Caleshu, C., Kingham, K., Klein, T. E., Whirl-Carrillo, M., Sakamoto, K., Wheeler, M. T., Butte, A. J., Ford, J. M., Boxer, L., Ioannidis, J. P., Yeung, A. C., Altman, R. B., Assimes, T. L., Snyder, M., Ashley, E. A., Quertermous, T. 2014; 311 (10): 1035-1045 Whole-genome sequencing (WGS) is increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication.To examine coverage and concordance of clinically relevant genetic variation provided by WGS technologies; to quantitate inherited disease risk and pharmacogenomic findings in WGS data and resources required for their discovery and interpretation; and to evaluate clinical action prompted by WGS findings.An exploratory study of 12 adult participants recruited at Stanford University Medical Center who underwent WGS between November 2011 and March 2012. A multidisciplinary team reviewed all potentially reportable genetic findings. Five physicians proposed initial clinical follow-up based on the genetic findings.Genome coverage and sequencing platform concordance in different categories of genetic disease risk, person-hours spent curating candidate disease-risk variants, interpretation agreement between trained curators and disease genetics databases, burden of inherited disease risk and pharmacogenomic findings, and burden and interrater agreement of proposed clinical follow-up.Depending on sequencing platform, 10% to 19% of inherited disease genes were not covered to accepted standards for single nucleotide variant discovery. Genotype concordance was high for previously described single nucleotide genetic variants (99%-100%) but low for small insertion/deletion variants (53%-59%). Curation of 90 to 127 genetic variants in each participant required a median of 54 minutes (range, 5-223 minutes) per genetic variant, resulted in moderate classification agreement between professionals (Gross , 0.52; 95% CI, 0.40-0.64), and reclassified 69% of genetic variants cataloged as disease causing in mutation databases to variants of uncertain or lesser significance. Two to 6 personal disease-risk findings were discovered in each participant, including 1 frameshift deletion in the BRCA1 gene implicated in hereditary breast and ovarian cancer. Physician review of sequencing findings prompted consideration of a median of 1 to 3 initial diagnostic tests and referrals per participant, with fair interrater agreement about the suitability of WGS findings for clinical follow-up (Fleiss , 0.24; P<001).In this exploratory study of 12 volunteer adults, the use of WGS was associated with incomplete coverage of inherited disease genes, low reproducibility of detection of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable findings. In certain cases, WGS will identify clinically actionable genetic variants warranting early medical intervention. These issues should be considered when determining the role of WGS in clinical medicine. View details for DOI 10.1001/jama.2014.1717 Clinical interpretation and implications of whole-genome sequencing. JAMA Dewey, F. E., Grove, M. E., Pan, C., Goldstein, B. A., Bernstein, J. A., Chaib, H., Merker, J. D., Goldfeder, R. L., Enns, G. M., David, S. P., Pakdaman, N., Ormond, K. E., Caleshu, C., Kingham, K., Klein, T. E., Whirl-Carrillo, M., Sakamoto, K., Wheeler, M. T., Butte, A. J., Ford, J. M., Boxer, L., Ioannidis, J. P., Yeung, A. C., Altman, R. B., Assimes, T. L., Snyder, M., Ashley, E. A., Quertermous, T. 2014; 311 (10): 1035-1045 MUTATIONS IN NGLY1 CAUSE AN INHERITED DISORDER OF THE ENDOPLASMIC RETICULUM-ASSOCIATED DEGRADATION (ERAD) PATHWAY Enns, G. M., Shashi, V., Zahir, F., Gambello, M. J., Bainbridge, M. N., Bast, T., Crimian, R., Schoch, K., Zoghbi, H. Y., Platt, J., Cox, R., Bernstein, J., Scavina, M., Walter, R. S., Need, A. C., Oviedo, A., Langlois, S., Bibb, A., Jones, M., Hedge, M., Gibbs, R. A., Schaaf, C. P., Boyle, S., Butte, A. J., Clark, M., Cowan, T., He, P., Snyder, M., Freeze, H. H., Goldstein, D. B., FORGE Canada Consortium ACADEMIC PRESS INC ELSEVIER SCIENCE. 2014: 23637 PRENATAL TREATMENT OF ORNITHINE TRANSCARBAMYLASE DEFICIENCY Wilnai, Y., Alcorn, D., Benitz, W., Berquist, W., Bernstein, J., Blumenfeld, Y. J., Castillo, R., Concepcion, W., Cowan, T., Cox, K. L., Cusmano, K., Deirdre, L., Esquival, C., Hintz, S. R., Homeyer, M., Hudgins, L., Palma, J., Summar, M. L., Schelley, S., Vishnu, P., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2014: 248 Severe and rapid disease course in the natural history of infants with lysosomal acid lipase deficiency Jones, S. A., Bernstein, D., Bialer, M., Dhawan, A., Hendriksz, C., Whitley, C. B., Banikazemi, M., Chang, A., Guardamagna, O., Raiman, J., Gamal, I., Selim, L., Cederbaum, S., Di Rocco, M., Domm, J., Enns, G., Finegold, D., Gargus, J., Zaki, O., Eckert, S., Schneider, E., Quinn, A. G., Valayannopouloss, V. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2014: S57S58 Practice patterns of mitochondrial disease physicians in North America. Part 1: Diagnostic and clinical challenges. Mitochondrion Parikh, S., Goldstein, A., Koenig, M. K., Scaglia, F., Enns, G. M., Saneto, R. 2014; 14 (1): 26-33 Mitochondrial medicine is a young subspecialty. Clinicians have a limited evidence base on which to formulate clinical decisions regarding diagnosis, treatment and patient management. Mitochondrial medicine specialists have cobbled together an informal set of rules and paradigms for preventive care and management based in part on anecdotal experience. The Mitochondrial Medicine Society (MMS) assessed the current state of clinical practice from diagnosis, to preventive care and treatment, as provided by various mitochondrial disease specialists in North America. We hope that by obtaining this information we can begin moving towards formulating a set of consensus criteria and establishing standards of care. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency. Molecular genetics and metabolism reports Niemi, A., Brown, C., Moore, T., Enns, G. M., Cowan, T. M. 2014; 1: 129-132 The pathophysiology of succinic semialdehyde dehydrogenase (SSADH) deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH), and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients. Severe multi-systemic presentation of COX10 deficiency Wilnai, Y., Cox, R., Bai, R., Enns, G. M. ELSEVIER SCI LTD. 2013: 926 Practice patterns of mitochondrial disease physicians in North America. Part 2: treatment, care and management MITOCHONDRION Parikh, S., Goldstein, A., Koenig, M. K., Scaglia, F., Enns, G. M., Saneto, R. 2013; 13 (6): 681-687 Mitochondrial medicine is a young subspecialty. Clinicians have limited evidence-based guidelines on which to formulate clinical decisions regarding diagnosis, treatment and management for patients with mitochondrial disorders. Mitochondrial medicine specialists have cobbled together an informal set of rules and paradigms for preventive care and management based in part on anecdotal experience. The Mitochondrial Medicine Society (MMS) assessed the current state of clinical practice including diagnosis, preventive care and treatment, as provided by various mitochondrial disease providers in North America. In this second of two reports, we present data related to clinical practice that highlight the challenges clinicians face in the routine care of patients with established mitochondrial disease. Concerning variability in treatment and preventative care approaches were noted. We hope that sharing this information will be a first step toward formulating a set of consensus criteria and establishing standards of care. View details for DOI 10.1016/j.mito2013.09.003 Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene MOLECULAR GENETICS AND METABOLISM Chanprasert, S., Wang, J., Weng, S., Enns, G. M., Boue, D. R., Wong, B. L., Mendell, J. R., Perry, D. A., Sahenk, Z., Craigen, W. J., Climent Alcala, F. J., Pascual, J. M., Melancon, S., Zhang, V. W., Scaglia, F., Wong, L. C. 2013; 110 (1-2): 153-161 Mitochondrial DNA (mtDNA) depletion syndromes (MDSs) are a clinically and molecularly heterogeneous group of mitochondrial cytopathies characterized by severe mtDNA copy number reduction in affected tissues. Clinically, MDSs are mainly categorized as myopathic, encephalomyopathic, hepatocerebral, or multi-systemic forms. To date, the myopathic form of MDS is mainly caused by mutations in the TK2 gene, which encodes thymidine kinase 2, the first and rate limiting step enzyme in the phosphorylation of pyrimidine nucleosides. We analyzed 9 unrelated families with 11 affected subjects exhibiting the myopathic form of MDS, by sequencing the TK2 gene. Twelve mutations including 4 novel mutations were detected in 9 families. Skeletal muscle specimens were available from 7 out of 11 subjects. Respiratory chain enzymatic activities in skeletal muscle were measured in 6 subjects, and enzymatic activities were reduced in 3 subjects. Quantitative analysis of mtDNA content in skeletal muscle was performed in 5 subjects, and marked mtDNA content reduction was observed in each. In addition, we outline the molecular and clinical characteristics of this syndrome in a total of 52 patients including those previously reported, and a total of 36 TK2 mutations are summarized. Clinically, hypotonia and proximal muscle weakness are the major phenotypes present in all subjects. In summary, our study expands the molecular and clinical spectrum associated with TK2 deficiency. Clinical Effect and Safety Profile of Recombinant Human Lysosomal Acid Lipase in Patients With Cholesteryl Ester Storage Disease HEPATOLOGY Balwani, M., Breen, C., Enns, G. M., Deegan, P. B., Honzik, T., Jones, S., Kane, J. P., Malinova, V., Sharma, R., Stock, E. O., Valayannopoulos, V., Wraith, J. E., Burg, J., Eckert, S., Schneider, E., Quinn, A. G. 2013; 58 (3): 950-957 Cholesteryl ester storage disease (CESD), an inherited deficiency of lysosomal acid lipase (LAL), is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. To assess the clinical effects and safety of the recombinant human LAL, sebelipase alfa, nine patients received four once-weekly infusions (0.35, 1, or 3 mgkg(-1) ) in LAL-CL01, which is the first human study of this investigational agent. Patients completing LAL-CL01 were eligible to enroll in the extension study (LAL-CL04) in which they again received four once-weekly infusions of sebelipase alfa (0.35, 1, or 3 mgkg(-1) ) before transitioning to long-term every-other-week infusions (1 or 3 mgkg(-1) ). Sebelipase alfa was well tolerated, with mostly mild adverse events unrelated to sebelipase alfa. No antidrug antibodies were detected. Transaminases decreased in patients in LAL-CL01 and increased between studies. In seven patients receiving ongoing sebelipase alfa treatment in LAL-CL04, the mean standard deviation (SD) decreases for alanine transaminase and aspartate aminotransferase at week 12 compared to the baseline values in LAL-CL01 were 46 21 U/L (-52%) and 21 14 U/L (-36%), respectively (P 0.05). Through week 12 of LAL-CL04, these seven patients also showed mean decreases from baseline in total cholesterol of 44 41 mg/dL (-22%; P = 0.047), low density lipoprotein-cholesterol of 29 31 mg/dL (-27%; P = 0.078), and triglycerides of 50 38 mg/dL (-28%, P = 0.016) and increases in high density lipoprotein-cholesterol of 5 mg/dL (15%; P = 0.016). Conclusion: These data establish that sebelipase alfa, an investigational enzyme replacement, in patients with CESD is well tolerated, rapidly decreases serum transaminases, and that these improvements are sustained with long-term dosing and are accompanied by improvements in serum lipid profile. View details for DOI 10.1002/hep.26289 Molecular and clinical characterization of the myopathic form of mitochondrial DNA depletion syndrome caused by mutations in the thymidine kinase (TK2) gene. Molecular genetics and metabolism Chanprasert, S., Wang, J., Weng, S., Enns, G. M., Bou, D. R., Wong, B. L., Mendell, J. R., Perry, D. A., Sahenk, Z., Craigen, W. J., Alcala, F. J., Pascual, J. M., Melancon, S., Zhang, V. W., Scaglia, F., Wong, L. C. 2013; 110 (1-2): 153-161 Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Manoli, I., Sysol, J. R., Li, L., Houillier, P., Garone, C., Wang, C., Zerfas, P. M., Cusmano-Ozog, K., Young, S., Trivedi, N. S., Cheng, J., Sloan, J. L., Chandler, R. J., Abu-Asab, M., Tsokos, M., Elkahloun, A. G., Rosen, S., Enns, G. M., Berry, G. T., Hoffmann, V., DiMauro, S., Schnermann, J., Venditti, C. P. 2013; 110 (33): 13552-13557 Isolated methylmalonic acidemia (MMA), caused by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by end stage renal disease that is resistant to conventional therapies, including liver transplantation. To establish a viable model of MMA renal disease, Mut was expressed in the liver of Mut(-/-) mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut(-/-);Tg(INS-Alb-Mut) mice, although completely rescued from neonatal lethality that was displayed by Mut(-/-) mice, manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstitial nephritis and ultrastructural changes in the proximal tubule mitochondria associated with aberrant tubular function, as demonstrated by single-nephron GFR studies. Microarray analysis of Mut(-/-);Tg(INS-Alb-Mut) kidneys identified numerous biomarkers, including lipocalin-2, which was then used to monitor the response of the GFR to antioxidant therapy in the mouse model. Renal biopsies and biomarker analysis from a large and diverse patient cohort (ClinicalTrials.gov identifier: NCT00078078) precisely replicated the findings in the animals, establishing Mut(-/-);Tg(INS-Alb-Mut) mice as a unique model of MMA renal disease. Our studies suggest proximal tubular mitochondrial dysfunction is a key pathogenic mechanism of MMA-associated kidney disease, identify lipocalin-2 as a biomarker of increased oxidative stress in the renal tubule, and demonstrate that antioxidants can attenuate the renal disease of MMA. Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism MOLECULAR GENETICS AND METABOLISM Camp, K. M., Lloyd-Puryear, M. A., Yao, L., Groft, S. C., Parisi, M. A., Mulberg, A., Gopal-Srivastava, R., Cederbaum, S., Enns, G. M., Ershow, A. G., Frazier, D. M., Gohagan, J., Harding, C., Howell, R. R., Regan, K., Stacpoole, P. W., Venditti, C., Vockley, J., Watson, M., Coates, P. M. 2013; 109 (4): 319-328 A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers. Glutathione: A redox signature in monitoring EPI-743 therapy in children with mitochondrial encephalomyopathies MOLECULAR GENETICS AND METABOLISM Pastore, A., Petrillo, S., Tozzi, G., Carrozzo, R., Martinelli, D., Dionisi-Vici, C., Di Giovamberardino, G., Ceravolo, F., Klein, M. B., Miller, G., Enns, G. M., Bertini, E., Piemonte, F. 2013; 109 (2): 208-214 Genetically defined Leigh syndrome (LS) is a rare, fatal inherited neurodegenerative disorder that predominantly affects children. Although mitochondrial dysfunction has clearly been associated with oxidative stress, few studies have specifically examined Leigh syndrome patients' blood glutathione levels. In this study, we analyzed the balance between oxidized and reduced glutathione in lymphocytes of 10 patients with genetically confirmed LS and monitored the effects of glutathione status following 6 months of treatment with EPI-743, a novel redox therapeutic.Lymphocytes were obtained from blood samples of 10 children with a genetically confirmed diagnosis of LS and in 20 healthy subjects. Total, reduced, oxidized and protein-bound glutathione levels were determined by HPLC analysis. Erythrocyte superoxide dismutase and glutathione peroxidase enzyme activities were measured by spectrophotometric assays. Plasma total thiols, carbonyl contents and malondialdehyde were assessed by spectrophotometric and fluorometric assays.A significant impairment of all glutathione forms was detected in patients, including a profound decrease of total and reduced glutathione (GSH) associated with high levels of all oxidized glutathione forms (GSSG+GS-Pro; OX). These findings negatively correlated with the glutathione peroxidase activity, which underwent a significant decrease in patients. After treatment with EPI-743, all patients showed a significant increase in reduced glutathione levels and 96% decrease of OX/GSH ratio.The data presented here strongly support glutathione as a "redox blood signature" in mitochondrial disorders and its use as a clinical trial endpoint in the development of mitochondrial disease therapies. Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders GENETICS IN MEDICINE Cui, H., Li, F., Chen, D., Wang, G., Truong, C. K., Enns, G. M., Graham, B., Milone, M., Landsverk, M. L., Wang, J., Zhang, W., Wong, L. C. 2013; 15 (5): 388-394 Purpose:The application of massively parallel sequencing technology to the analysis of the mitochondrial genome has demonstrated great improvement in the molecular diagnosis of mitochondrial DNA-related disorders. The objective of this study was to investigate the performance characteristics and to gain new insights into the analysis of the mitochondrial genome.Methods:The entire mitochondrial genome was analyzed as a single amplicon using a long-range PCR-based enrichment approach coupled with massively parallel sequencing. The interference of the nuclear mitochondrial DNA homologs was distinguished from the actual mitochondrial DNA sequences by comparison with the results obtained from conventional PCR-based Sanger sequencing using multiple pairs of primers.Results:Our results demonstrated the uniform coverage of the entire mitochondrial genome. Massively parallel sequencing of the single amplicon revealed the presence of single-nucleotide polymorphisms and nuclear homologs of mtDNA sequences that cause the erroneous and inaccurate variant calls when PCR/Sanger sequencing approach was used. This single amplicon massively parallel sequencing strategy provides an accurate quantification of mutation heteroplasmy as well as the detection and mapping of mitochondrial DNA deletions.Conclusion:The ability to quantitatively and qualitatively evaluate every single base of the entire mitochondrial genome is indispensible to the accurate molecular diagnosis and genetic counseling of mitochondrial DNA-related disorders. This new approach may be considered as first-line testing for comprehensive analysis of the mitochondrial genome.Genet Med 2013:15(5):388-394. Mutations in B3GALNT2 Cause Congenital Muscular Dystrophy and Hypoglycosylation of alpha-Dystroglycan AMERICAN JOURNAL OF HUMAN GENETICS Stevens, E., Carss, K. J., Cirak, S., Foley, R., Torelli, S., Willer, T., Tambunan, D. E., Yau, S., Brodd, L., Sewry, C. A., Feng, L., Haliloglu, G., Orhan, D., Dobyns, W. B., Enns, G. M., Manning, M., Krause, A., Salih, M. A., Walsh, C. A., Hurles, M., Campbell, K. P., Manzini, M. C., Stemple, D., Lin, Y., Muntoni, F. 2013; 92 (3): 354-365 Mutations in several known or putative glycosyltransferases cause glycosylation defects in -dystroglycan (-DG), an integral component of the dystrophin glycoprotein complex. The hypoglycosylation reduces the ability of -DG to bind laminin and other extracellular matrix ligands and is responsible for the pathogenesis of an inherited subset of muscular dystrophies known as the dystroglycanopathies. By exome and Sanger sequencing we identified two individuals affected by a dystroglycanopathy with mutations in -1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2). B3GALNT2 transfers N-acetyl galactosamine (GalNAc) in a -1,3 linkage to N-acetyl glucosamine (GlcNAc). A subsequent study of a separate cohort of individuals identified recessive mutations in four additional cases that were all affected by dystroglycanopathy with structural brain involvement. We show that functional dystroglycan glycosylation was reduced in the fibroblasts and muscle (when available) of these individuals via flow cytometry, immunoblotting, and immunocytochemistry. B3GALNT2 localized to the endoplasmic reticulum, and this localization was perturbed by some of the missense mutations identified. Moreover, knockdown of b3galnt2 in zebrafish recapitulated the human congenital muscular dystrophy phenotype with reduced motility, brain abnormalities, and disordered muscle fibers with evidence of damage to both the myosepta and the sarcolemma. Functional dystroglycan glycosylation was also reduced in the b3galnt2 knockdown zebrafish embryos. Together these results demonstrate a role for B3GALNT2 in the glycosylation of -DG and show that B3GALNT2 mutations can cause dystroglycanopathy with muscle and brain involvement. Liver transplantation for urea cycle disorders in pediatric patients: A single-center experience PEDIATRIC TRANSPLANTATION Kim, I. K., Niemi, A., Krueger, C., Bonham, C. A., Concepcion, W., Cowan, T. M., Enns, G. M., Esquivel, C. O. 2013; 17 (2): 158-167 LT has emerged as a surgical treatment for UCDs. We hypothesize that LT can be safely and broadly utilized in the pediatric population to effectively prevent hyperammonemic crises and potentially improve neurocognitive outcomes. To determine the long-term outcomes of LT for UCDs, charts of children with UCD who underwent LT were retrospectively reviewed at an academic institution between July 2001 and May 2012. A total of 23 patients with UCD underwent LT at a mean age of 3.4 yr. Fifteen (65%) patients received a whole-liver graft, seven patients (30%) received a reduced-size graft, and one patient received a living donor graft. Mean five-yr patient survival was 100%, and allograft survival was 96%. Mean peak blood ammonia (NH(3) ) at presentation was 772 mol/L (median 500, range 178-2969, normal <30-50). After transplantation, there were no episodes of hyperammonemia. Eleven patients were diagnosed with some degree of developmental delay before transplantation, which remained stable or improved after transplantation. Patients without developmental delay before transplantation maintained their cognitive abilities at long-term follow-up. LT was associated with the eradication of hyperammonemia, removal of dietary restrictions, and potentially improved neurocognitive development. Long-term follow-up is underway to evaluate whether LT at an early age (<1 yr) will attain improved neurodevelopmental outcomes. Long term safety and clinical activity of SBC-102, a recombinant human lysosomal acid lipase (rhLAL), in patients with late onset LAL deficiency 9th Annual Research Meeting of the Lysosomal-Disease-Network (LDN) Balwani, M., Malinova, V., Sharma, R., Valayannopoulos, V., Stock, E. O., Boyadjiev, S. A., Kessler, B., Deegan, P., Enns, G. M., Breen, C., Kane, J. P., Schneider, E., Quinn, A. G. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2013: S22S23 ARTHROGRYPOSIS, RENAL DYSFUNCTION AND CHOLESTASIS (ARC) SYNDROME: A NEW PATIENT CASE REPORT Western Regional Meeting of the American-Federation-for-Medical-Research Brennan, M., SLATTERY, L., Esplin, E., Enns, G. M., Hudgins, L., Manning, M. LIPPINCOTT WILLIAMS & WILKINS. 2013: 18888 Pediatric Liver Transplantation as Definitive Therapy for Urea Cycle Disorders 13th Annual State of the Art Winter Symposium of the American-Society-of-Transplant-Surgeons (ASTS) Held in Conjunction with the NATCO Symposium for Advanced Transplant Professionals Kim, I. K., Niemi, A., Krueger, C., Enns, G., Esquivel, C. O. WILEY-BLACKWELL. 2013: 8686 Enzyme Replacement with Recombinant Human Lysosomal Acid Lipase (rhLAL) in Patients with Cholesteryl Ester Storage Disease, the Late Onset Form of LAL Deficiency, Produces Sustained Decreases in Transaminases and Reduction in Liver Fat Content 63rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) Jones, S., Enns, G. M., Balwani, M., Breen, C., Sharma, R., Deegan, P., Malinova, V., Honzik, T., Valayannopoulos, V., Schneider, E., Burg, J., Quinn, A. G. WILEY-BLACKWELL. 2012: 824A825A Atypical Amyoplasia Congenita in an Infant With Leigh Syndrome: A Mitochondrial Cause of Severe Contractures? AMERICAN JOURNAL OF MEDICAL GENETICS PART A Wilnai, Y., Seaver, L. H., Enns, G. M. 2012; 158A (9): 2353-2357 Amyoplasia congenita is a distinct form of arthrogryposis with characteristic features including internally rotated and adducted shoulders, extended elbows, flexion, and ulnar deviation of the wrists, and adducted thumbs. Fetal hypokinesia, secondary to a variety of genetic conditions, neuromuscular disorders, and environmental agents, is associated with contractures. In order to increase our understanding of the phenotypic spectrum associated with SURF 1 deficiency, a common cause of mitochondrial respiratory chain complex IV deficiency and Leigh syndrome, we describe a now 6-year-old boy who presented in the neonatal period with amyoplasia congenita. His development was normal until age 10.5 months, at which time he developed severe hypotonia and choreoathetosis following an episode of viral gastroenteritis. Following the onset of neurological symptoms, he gradually developed severe kyphosis and lower limb contractures. Blood and cerebrospinal fluid lactate levels were elevated and head imaging showed characteristic features of Leigh syndrome. He was found to harbor two pathogenic heterozygous mutations in the SURF 1 gene. In this case, mitochondrial dysfunction and the resultant energy deficiency may have played a role in causing abnormal neuronal development during embryogenesis, causing arthrogryposis. A variety of mitochondrial respiratory chain complex deficiencies have been associated with contractures of varying severity. Therefore, mitochondrial disorders should be considered in the differential diagnosis of neonatal arthrogryposis, especially if other characteristic findings such as lactic acidemia or basal ganglia abnormalities are present. View details for DOI 10.1002/ajmg.a.35533 RECOMBINANT HUMAN LYSOSOMAL ACID LIPASE (LAL) DEMONSTRATES PHARMACODYNAMIC ACTIVITY IN CHOLESTERYL ESTER STORAGE DISEASE (CESD), THE LATE ONSET FORM OF LAL DEFICIENCY Jones, S., Enns, G., Balwani, M., Breen, C., Sharma, R., Deegan, P., Malinova, V., Honzik, T., Valayannopoulos, V., Schneider, E., Burg, J., Quinn, A. G. SPRINGER. 2012: S11S11 Improved redox status after liver transplantation in a patient with MMA mut(0) subtype; functional evidence for EPI-743 therapy Niemi, A., Niemi, A., Moore, T., Cowan, T., Kheifets, V., Enns, G. M. ELSEVIER SCI LTD. 2012: 55757 Outcome of infants diagnosed with 3-methyl-crotonyl-CoA-carboxylase deficiency by newborn screening MOLECULAR GENETICS AND METABOLISM Arnold, G. L., Salazar, D., Neidich, J. A., Suwannarat, P., Graham, B. H., Lichter-Konecki, U., Bosch, A. M., Cusmano-Ozog, K., Enns, G., Wright, E. L., Lanpher, B. C., Owen, N. N., Lipson, M. H., Cerone, R., Levy, P., Wong, L. C., Dezsofi, A. 2012; 106 (4): 439-441 3-Methyl CoA carboxylase (3-MCC) deficiency is an inborn error of metabolism in the catabolism of the amino acid leucine. Original reports suggested this disorder was associated with significant neurological and biochemical effects. However newborn screening has identified a higher than expected incidence of this disorder with apparent normal outcome in most cases.A retrospective analysis of thirty-five cases of 3-MCC deficiency identified by newborn screening and diagnosed by enzyme or molecular analysis.There was a strong inverse correlation between initial C5OH level and residual enzyme activity. A few reports of hypoglycemia, ketosis, poor feeding/failure to thrive or fasting intolerance were reported, but there was no clear relationship between symptoms and residual enzyme activity. Developmental outcome included several children with mental retardation (including one with Down syndrome and one with schizencephaly) and two with Autism Spectrum disorders but there was no apparent relationship to residual enzyme activity. Free carnitine deficiency was relatively common.Although residual enzyme activity was clearly related to metabolite elevation, there was no apparent relationship with other measures of outcome. The number of reports of neurologic abnormalities or metabolic symptoms (poor feeding, hypoglycemia, fasting intolerance, etc.) is concerning, but the significance is unclear in this retrospective sample. Pediatric Liver Transplantation as Definitive Therapy for Urea Cycle Disorders 24th Annual Meeting of the European-Association-for-Cardiothoracic-Surgery Kim, I., Niemi, A., Enns, G., Esquivel, C. WILEY-BLACKWELL. 2012: 344344 Propionic acidemia: To liver transplant or not to liver transplant? PEDIATRIC TRANSPLANTATION Chapman, K. A., Summar, M. L., Enns, G. M. 2012; 16 (3): 209-210 Low glutathione levels in a patient with succinic semialdehyde dehydrogenase (SSADH) deficiency 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD) Niemi, A., Brown, C., Moore, T., Enns, G. M., Cowan, T. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2012: 34545 Mutations in KAT6B, Encoding a Histone Acetyltransferase, Cause Genitopatellar Syndrome AMERICAN JOURNAL OF HUMAN GENETICS Campeau, P. M., Kim, J. C., Lu, J. T., Schwartzentruber, J. A., Abdul-Rahman, O. A., Schlaubitz, S., Murdock, D. M., Jiang, M., Lammer, E. J., Enns, G. M., Rhead, W. J., Rowland, J., Robertson, S. P., Cormier-Daire, V., Bainbridge, M. N., Yang, X., Gingras, M., Gibbs, R. A., Rosenblatt, D. S., Majewski, J., Lee, B. H. 2012; 90 (2): 282-289 Genitopatellar syndrome (GPS) is a skeletal dysplasia with cerebral and genital anomalies for which the molecular basis has not yet been determined. By exome sequencing, we found de novo heterozygous truncating mutations in KAT6B (lysine acetyltransferase 6B, formerly known as MYST4 and MORF) in three subjects; then by Sanger sequencing of KAT6B, we found similar mutations in three additional subjects. The mutant transcripts do not undergo nonsense-mediated decay in cells from subjects with GPS. In addition, human pathological analyses and mouse expression studies point to systemic roles of KAT6B in controlling organismal growth and development. Myst4 (the mouse orthologous gene) is expressed in mouse tissues corresponding to those affected by GPS. Phenotypic differences and similarities between GPS, the Say-Barber-Biesecker variant of Ohdo syndrome (caused by different mutations of KAT6B), and Rubinstein-Taybi syndrome (caused by mutations in other histone acetyltransferases) are discussed. Together, the data support an epigenetic dysregulation of the limb, brain, and genital developmental programs. Initial Human Experience with SBC-102, a Recombinant Enzyme Replacement Therapy in Adults with Lysosomal Acid Lipase Deficiency 8th Annual World Symposium of the Lysosomal Disease Network Enns, G., Balwani, M., Deegan, P., Malinova, V. R., Honzik, H., Sharma, R., Valayannopoulos, V., Wraith, E., Schneider, E., Burg, J., Quinn, A. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2012: S29S29 Natural history of propionic acidemia MOLECULAR GENETICS AND METABOLISM Pena, L., Franks, J., Chapman, K. A., Gropman, A., Mew, N. A., Chakrapani, A., Island, E., MacLeod, E., Matern, D., Smith, B., Stagni, K., Sutton, V. R., Ueda, K., Urv, T., Venditti, C., Enns, G. M., Summar, M. L. 2012; 105 (1): 5-9 Propionic acidemia is an organic acidemia that can lead to metabolic acidosis, coma and death, if not treated appropriately in the acute setting. Recent advancements in treatment have allowed patients with propionic acidemia to live beyond the neonatal period and acute presentation. The natural history of the disease is just beginning to be elucidated as individuals reach older ages. Recent studies have identified the genomic mutations in the genes PCCA and PCCB. However, as of yet no clear genotype-phenotype correlations are known. As patients age, the natural progression of propionic acidemia illuminates intellectual difficulties, increased risk for neurological complications, including stroke-like episodes, cardiac complications, and gastrointestinal difficulties, as well as a number of other complications. This article reviews the available literature for the natural history of propionic acidemia. A Novel Mutation in the HSD17B10 Gene of a 10-Year-Old Boy with Refractory Epilepsy, Choreoathetosis and Learning Disability PLOS ONE Seaver, L. H., He, X., Abe, K., Cowan, T., Enns, G. M., Sweetman, L., Philipp, M., Lee, S., Malik, M., Yang, S. 2011; 6 (11) Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this gene result in HSD10 deficiency, whereas a silent mutation results in mental retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense mutation found in the HSD17B10 gene, namely c.194T>C transition (rs104886492), brought about by the loss of two forked methyl groups of valine 65 in the HSD10 active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a neurological syndrome with metabolic derangements, choreoathetosis, refractory epilepsy and learning disability. He has no history of acute decompensation or metabolic acidosis whereas his urine organic acid profile, showing elevated levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of HSD10 deficiency. His HSD10 activity was much lower than the normal control level, with normal -ketothiolase activity. The c.194T>C mutation in HSD17B10 can be identified by the restriction fragment polymorphism analysis, thereby facilitating the screening of this novel mutation in individuals with intellectual disability of unknown etiology and their family members much easier. The patient's mother is an asymptomatic carrier, and has a mixed ancestry (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency patients are not confined to a particular ethnicity although previously reported cases were either Spanish or German descendants. Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development PSYCHOPHARMACOLOGY Casper, R. C., Gilles, A. A., Fleisher, B. E., Baran, J., Enns, G., Lazzeroni, L. C. 2011; 217 (2): 211-219 This study evaluated the question whether length of in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants might affect neonatal outcome and psychomotor development in infancy.Birth outcome was determined in the offspring of 55 women with major depressive disorder who used SSRI medication for different durations during their pregnancies. At an average age of 14months, children underwent a pediatric examination and an evaluation with the Bayley Scales of Infant Development (BSID-II).Duration of in utero exposure to SSRIs was negatively associated with total Apgar scores, specifically the activity subscale. Odds ratios for a low score (<2) on this scale were 3.8 and 6.0 at 1 and 5min, respectively. Newborns with longer exposure were more often admitted to the Neonatal Intensive Care Unit (p<.03). Mental Development Index scores of the infants were not associated with the length of gestational exposure to SSRIs. A longer duration of exposure increased the risk for lower Psychomotor Developmental Index and Behavioral Rating Scale scores in infancy (p=0.012 and p=0.007, respectively) on the BSID-II.The findings provide evidence that the length of prenatal SSRI antidepressant use can affect neonatal adjustment and can have an effect on psychomotor test scores in infancy. Importantly, the children's mental development and motor function by neurological examination were within the normal range. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations. View details for DOI 10.1007/s00213-011-2270-z alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Shrader, W. D., Amagata, A., Barnes, A., Enns, G. M., Hinman, A., Jankowski, O., Kheifets, V., Komatsuzaki, R., Lee, E., Mollard, P., Murase, K., Sadun, A. A., Thoolen, M., Wesson, K., Miller, G. 2011; 21 (12): 3693-3698 We report that -tocotrienol quinone (ATQ3) is a metabolite of -tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function. View details for DOI 10.1016/j.bmcl.2011.04.085 Clinical Report-Health Supervision for Children With Fragile X Syndrome PEDIATRICS Hersh, J. H., Saul, R. A., Saal, H. M., Braddock, S. R., Enns, G. M., Gruen, J. R., Perrin, J. M., Tarini, B. A., Hanson, J. W., Lloyd-Puryear, M. A., Musci, T. J., Rasmussen, S. A., Spire, P. 2011; 127 (5): 994-1006 View details for DOI 10.1542/peds.2010-3500 Long-term follow-up of a patient with early onset CBLG disease 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) Niemi, A. K., Cusmano-Ozog, K., Rosenblatt, D. S., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2011: 3067 Baseline characteristics of PKU patients enrolled in the PKUDOS registry 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) Burton, B. K., Longo, N., Arnold, G. L., Enns, G. M., Andersson, H. C., Mofidi, S., Peck, D., Prado, B. C., Pridjian, G., Waisbren, S., White, D. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2011: 27373 MITOCHONDRIAL PATHOLOGY IN ANGELMAN SYNDROME Western Regional Meeting of the American-Federation-for-Medical-Research Niemi, A., Cox, R., Scharfe, C., Cherry, A., Enns, G. LIPPINCOTT WILLIAMS & WILKINS. 2011: 16566 Suboptimal outcomes in patients with PKU treated early with diet alone: Revisiting the evidence MOLECULAR GENETICS AND METABOLISM Enns, G. M., Koch, R., Brumm, V., Blakely, E., Suter, R., Jurecki, E. 2010; 101 (2-3): 99-109 The National Institute of Health (NIH) published a Consensus Statement on the screening and management of Phenylketonuria (PKU) in 2000. The panel involved in the development of this consensus statement acknowledged the lack of data regarding the potential for more subtle suboptimal outcomes and the need for further research into treatment options. In subsequent years, the approval of new treatment options for PKU and outcome data for patients treated from the newborn period by dietary therapy alone have become available. We hypothesized that a review of the PKU literature since 2000 would provide further evidence related to neurocognitive, psychosocial, and physical outcomes that could serve as a basis for reassessment of the 2000 NIH Consensus Statement.A systematic review of literature residing in PubMed, Scopus and PsychInfo was performed in order to assess the outcome data over the last decade in diet-alone early-treated PKU patients to assess the need for new recommendations and validity of older recommendations in light of new evidence.The majority of publications (140/150) that contained primary outcome data presented at least one suboptimal outcome compared to control groups or standardized norms/reference values in at least one of the following areas: neurocognitive/psychosocial (N=60; 58 reporting suboptimal outcomes); quality of life (N=6; 4 reporting suboptimal outcomes); brain pathology (N=32; 30 reporting suboptimal outcomes); growth/nutrition (N=34; 29 reporting suboptimal outcomes); bone pathology (N=9; 9 reporting suboptimal outcomes); and/or maternal PKU (N=19; 19 reporting suboptimal outcomes).Despite the remarkable success of public health programs that have instituted newborn screening and early introduction of dietary therapy for PKU, there is a growing body of evidence that suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology and maternal PKU outcomes are suboptimal. The time may be right for revisiting the 2000 NIH Consensus Statement in order to address a number of important issues related to PKU management, including treatment advancements for metabolic control in PKU, blood Phe variability, neurocognitive and psychological assessments, routine screening measures for nutritional biomarkers, and bone pathology. Long-term outcome following pediatric liver transplantation for metabolic disorders PEDIATRIC TRANSPLANTATION Stevenson, T., Millan, M. T., Wayman, K., Berquist, W. E., Sarwal, M., Johnston, E. E., Esquivel, C. O., Enns, G. M. 2010; 14 (2): 268-275 In order to determine long-term outcome, including survival, growth and development, following liver transplantation in children with metabolic disorders, we retrospectively reviewed charts of 54 children with metabolic disorders evaluated from 1989-2005 for presenting symptoms, transplantation timing and indications, survival, metabolic parameters, growth, and development. Thirty-three patients underwent liver transplantation (12 received combined liver-kidney transplants) at a median age of 21 months. At a median follow-up of 3.6 yr, patient survival was 100%, and liver and kidney allograft survival was 92%, and 100%, respectively. For the group as a whole, weight Z scores improved and body mass index at follow-up was in the normal range. Two yr post-transplantation, psychomotor development improved significantly (p < 0.01), but mental skills did not; however, both indices were in the low-normal range of development. When compared to patients with biliary atresia, children with metabolic disorders showed significantly lower mental developmental scores at one and two yr post-transplantation (p < 0.05), but psychomotor developmental scores were not significantly different. We conclude that, in patients with metabolic disorders meeting indications for transplantation, liver transplantation or combined liver-kidney transplantation (for those with accompanying renal failure) is associated with excellent long-term survival, improved growth, and improved psychomotor development. Biomarkers of redox abnormalities in mitochondrial disorders and organic acidemias Atkuri, K. R., Cowan, T. M., Procaccio, V., Herzenberg, L. A., Enns, G. M. ELSEVIER SCI LTD. 2010: 2067 EVIDENCE OF REDOX IMBALANCE IN A PATIENT WITH METHYLMALONIC ACIDEMIA (mut0) 33rd Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2010) Cusmano-Ozog, K., Moore, T., Niemi, A., Zadeh, N., Cowan, T. M., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2010: 21011 Nitrogen sparing therapy revisited 2009 3rd International Satellite on Urea Cycle Disorders Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2010: S65S71 Although the protocol that most experienced metabolic centers in the United States follow for treating acute hyperammonemia in urea cycle disorders (UCDs) is similar to that proposed by Brusilow and Batshaw in the early 1980s, over the years a steady evolution has taken place. Continued developments in intensive care, surgical and hemodialysis techniques, fluid and electrolyte management, cardiovascular support, and emergency transport have contributed to improved management of acute hyperammonemia. Compared to historical data, survival of urea cycle patients has also improved following treatment with alternative pathway therapy, in addition to appropriate supportive care, including the provision of adequate calories to prevent catabolism and promote anabolism and hemodialysis if needed. However, overall neurological outcomes have been suboptimal. There are currently a number of exciting prospective new therapies on the horizon, including novel medications or cell-based treatments. Nevertheless, the therapeutic expertise that is currently in place at centers specializing in management of metabolic emergencies already has the potential to improve survival and outcome in these children significantly. The early identification of UCD patients so that transport to a metabolic treatment center may be carried out without delay continues to be a major area of focus and challenge. Future treatment strategies in phenylketonuria MOLECULAR GENETICS AND METABOLISM van Spronsen, F. J., Enns, G. M. 2010; 99: S90-S95 Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy. During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU. Pathological evidence of Wolman's disease following hematopoietic stem cell transplantation despite correction of lysosomal acid lipase activity BONE MARROW TRANSPLANTATION Gramatges, M. M., Dvorak, C. C., Regula, D. P., Enns, G. M., Weinberg, K., Agarwal, R. 2009; 44 (7): 449-450 View details for DOI 10.1038/bmt.2009.57 Hypoplastic Glomerulocystic Kidney Disease and Hepatoblastoma A Potential Association not Caused by Mutations in Hepatocyte Nuclear Factor 1 beta JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Abdul-Rahman, O. A., Edghill, E. L., Kwan, A., Enns, G. M., Hattersley, A. T. 2009; 31 (7): 527-529 Hypoplastic glomerulocystic kidney disease is an autosomal dominant disorder caused by mutations in hepatocyte nuclear factor-1beta. Hepatoblastoma is a sporadic occurring tumor of embryonal origin that has been associated with the several overgrowth syndromes. We report a case of concomitant hypoplastic glomerulocystic kidney disease and hepatoblastoma. Review of the literature identified 4 other patients with a similar association. We propose that hypoplastic glomerulocystic kidney disease and hepatoblastoma represent a possible association, and we excluded mutations in hepatocyte nuclear factor-1beta in our patient as causative of this putative association. Clinical and Molecular Heterogeneity in Patients with the CblD Inborn Error of Cobalamin Metabolism JOURNAL OF PEDIATRICS Miousse, I. R., Watkins, D., Coelho, D., Rupar, T., Crombez, E. A., Vilain, E., Bernstein, J. A., Cowan, T., Lee-Messer, C., Enns, G. M., Fowler, B., Rosenblatt, D. S. 2009; 154 (4): 551-556 To describe 3 patients with the cblD disorder, a rare inborn error of cobalamin metabolism caused by mutations in the MMADHC gene that can result in isolated homocystinuria, isolated methylmalonic aciduria, or combined homocystinuria and methylmalonic aciduria.Patient clinical records were reviewed. Biochemical and somatic cell genetic studies were performed on cultured fibroblasts. Sequence analysis of the MMADHC gene was performed on patient DNA.Patient 1 presented with isolated methylmalonic aciduria, patient 3 with isolated homocystinuria, and patient 2 with combined methylmalonic aciduria and homocystinuria. Studies of cultured fibroblasts confirmed decreased synthesis of adenosylcobalamin in patient 1, decreased synthesis of methylcobalamin in patient 3, and decreased synthesis of both cobalamin derivatives in patient 2. The diagnosis of cblD was established in each patient by complementation analysis. Mutations in the MMADHC gene were identified in all patients.The results emphasize the heterogeneous clinical, cellular and molecular phenotype of the cblD disorder. The results of molecular analysis of the MMADHC gene are consistent with the hypothesis that mutations affecting the N terminus of the MMADHC protein are associated with methylmalonic aciduria, and mutations affecting the C terminus are associated with homocystinuria. A novel homozygous SCO2 mutation, p.G193S, causing fatal infantile cardioencephalomyopathy CLINICAL NEUROPATHOLOGY Mobley, B. C., Enns, G. M., Wong, L., Vogel, H. 2009; 28 (2): 143-149 Cytochrome c oxidase (COX) deficiency is a frequent cause of mitochondrial disease in infants. Mutations in the COX assembly gene SCO2 cause fatal infantile cardioencephalomyopathy. All patients reported to date with SCO2 deficiency share a common p.E140K mutation in at least 1 allele. In order to further the understanding of the genotype-phenotype spectrum associated with fatal infantile cardioencephalomyopathy, we describe a novel homozygous SCO2 mutation p.G193S in a patient with fatal infantile cardioencephalomyopathy born to consanguineous parents of Indian ancestry. Successful pregnancy and cesarean delivery via noninvasive ventilation in mitochondrial myopathy JOURNAL OF PERINATOLOGY Yuan, N., El-Sayed, Y. Y., Ruoss, S. J., Riley, E., Enns, G. M., Robinson, T. E. 2009; 29 (2): 166-167 We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia. View details for DOI 10.1038/jp.2008.178 Neurologic Damage and Neurocognitive Dysfunction in Urea Cycle Disorders SEMINARS IN PEDIATRIC NEUROLOGY Enns, G. M. 2008; 15 (3): 132-139 Although the survival of patients who have urea cycle disorders has improved with the use of modalities such as alternative pathway therapy and hemodialysis, neurologic outcome is suboptimal. Patients often manifest with a variety of neurologic abnormalities, including cerebral edema, seizures, cognitive impairment, and psychiatric illness. Current hypotheses of the pathogenesis underlying brain dysfunction in these patients have focused on several lines of investigation, including the role of glutamine in causing cerebral edema, mitochondrial dysfunction leading to energy failure and the production of free radicals, and altered neurotransmitter metabolism. Advances in understanding the pathogenetic mechanisms underlying brain impairment in urea cycle disorders may lead to the development of therapies designed to interfere with the molecular cascade that ultimately leads to cerebral edema and other brain pathological findings. View details for DOI 10.1016/j.spen.2008.05.007 Cell-based therapies for metabolic liver disease MOLECULAR GENETICS AND METABOLISM Enns, G. M., Millan, M. T. 2008; 95 (1-2): 3-10 Liver transplantation is an important therapeutic option for many individuals with metabolic liver disease. Nevertheless, the invasive nature of surgery and limitations of donor organ availability have led to the search for alternatives to whole-organ transplantation. Cell-based therapies have been a particularly active area of investigation in recent years. Hepatocyte transplantations have been performed for a variety of indications, including acute liver failure, end-stage liver disease, and inborn errors of metabolism. Individuals with inborn errors of metabolism who have undergone hepatocyte transplantation have shown clinical improvement and partial correction of the underlying metabolic defect. In most cases, sustained benefits have not been observed. This may be related to inadequate cell dose, variations in the quality of hepatocyte preparations, rejection of the transplanted cells, or senescence of transplanted hepatocytes. Though initial proof of concept with hepatocyte transplantation has been demonstrated by a number of investigators, wide application of this technology has been hindered by the inability to secure a reliable and well-characterized cell source(s) for transplantation and by the challenges of sustained engraftment and expansion of transplanted cells in vivo. Cell-based therapies, including those based on stem cells or more differentiated progenitor cells, may represent the future of cell transplantation for treatment of metabolic liver disease. Maternal phenylketonuria PEDIATRICS Saal, H. M., Braddock, S. R., Bull, M. J., Enns, G., Gruen, J. R., Mendelsohn, N. J., Saul, R. A. 2008; 122 (2): 445-449 Dopa-responsive dystonia presenting as delayed and awkward gait PEDIATRIC NEUROLOGY Cheyette, B. N., Cheyette, S. N., Cusmano-Ozog, K., Enns, G. M. 2008; 38 (4): 273-275 Dopa-responsive dystonia is a hereditary disease characterized by inadequate dopamine production. Autosomal-dominant cases result from mutations in the GCH1 gene, encoding guanosine triphosphate (GTP)-cyclohydrolase 1. The most common presenting manifestation is dystonia of a lower extremity, often worsening late in the day. The onset and clinical severity are variable, sometimes even within a single family. Gender effects on allele penetrance have been reported. We present a male toddler with dopa-responsive dystonia caused by an autosomal-dominant GCH1 mutation. Three other family members were also found to carry the mutation, with widely different functional consequences. Central nervous system therapy for lysosomal storage disorders NEUROSURGICAL FOCUS Enns, G. M., Huhn, S. L. 2008; 24 (3-4) Most lysosomal storage disorders are characterized by progressive central nervous system impairment, with or without systemic involvement. Affected individuals have an array of symptoms related to brain dysfunction, the most devastating of which is neurodegeneration following a period of normal development. The blood-brain barrier has represented a significant impediment to developing therapeutic approaches to treat brain disease, but novel approaches-including enzyme replacement, small-molecule, gene, and cell-based therapies-have given children afflicted by these conditions and those who care for them hope for the future. View details for DOI 10.3171/FOC/2008/24/3-4/E11 Health supervision for children with neurofibromatosis PEDIATRICS Schaefer, G. B., Bull, M. J., Enns, G. M., Gruen, J. R., Hersh, J. H., Mendelsohn, N. J., Saal, H. M. 2008; 121 (3): 633-642 Neurofibromatosis 1 is a multisystem disorder that primarily involves the skin and nervous system. Its population prevalence is 1 in 3500. The condition usually is recognized in early childhood, when cutaneous manifestations are apparent. Although neurofibromatosis 1 is associated with marked clinical variability, most affected children do well from the standpoint of their growth and development. Some features of neurofibromatosis 1 are present at birth, and others are age-related abnormalities of tissue proliferation, which necessitate periodic monitoring to address ongoing health and developmental needs and to minimize the risk of serious medical complications. This clinical report provides a review of the clinical criteria needed to establish a diagnosis, the inheritance pattern of neurofibromatosis 1, its major clinical and developmental manifestations, and guidelines for monitoring and providing intervention to maximize the growth, development, and health of an affected child. Progressive cerebral vascular degeneration with mitochondrial encephalopathy AMERICAN JOURNAL OF MEDICAL GENETICS PART A Longo, N., Schrijver, I., Vogel, H., Pique, L. M., Cowan, T. M., Pasquali, M., Steinberg, G. K., Hedlund, G. L., Ernst, S. L., Gallagher, R. C., Enns, G. M. 2008; 146A (3): 361-367 MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a maternally inherited disorder characterized by recurrent cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with loss of consciousness and severe metabolic acidosis following vomiting and dehydration. She developed progressive sensorineural hearing loss, myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (hexanoylglycine and suberylglycine), but also severe lactic acidemia (10-25 mM) and, in urine, excess of lactic acid, intermediates of the citric cycle, and marked ketonuria, suggesting mitochondrial dysfunction. She progressed rapidly to develop temporary cortical blindness. Brain imaging indicated generalized atrophy, more marked on the left side, in addition to white matter alterations consistent with a mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A>G) and a second pathogenic mutation (233T>C). MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A>T mutation in tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that mitochondrial disorders may be associated with severe vascular disease resulting in Moyamoya syndrome. The contribution of the concomitant MCAD deficiency to the development of the phenotype in this case is unclear. Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase HUMAN MUTATION Dimmock, D. P., Zhang, Q., Dionisi-Vici, C., Carrozzo, R., Shieh, J., Tang, L. Y., Truong, C., Schmitt, E., Sifry-Platt, M., Lucioli, S., Santorelli, F. M., Ficicioglu, C. H., Rodriguez, M., Wierenga, K., Enns, G. M., Longo, N., Lipson, M. H., Valiance, H., Craigen, W. J., Scaglia, F., Wong, L. 2008; 29 (2): 330-331 Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology. View details for DOI 10.1002/humu.9519 An unusual case of Pompe disease presenting as muscular dystrophy Cusmano-Ozog, K., Vogel, H., Cowan, T., Enns, G. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2008: S18 Inborn error of metabolism presenting as malformation syndrome: Hydrocephalus as a manifestation of cobalamin D disease Western Regional Meeting of the American-Federation-for-Medical-Research Bernstein, J. A., Lee-Messer, C., Cusmano, K., Rosenblatt, D. S., Cowan, T., Enns, G. M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 19696 Glutaric acidemia type I: a neurosurgical perspective JOURNAL OF NEUROSURGERY Hou, L. C., Veeravagu, A., Hsu, A. R., Enns, G. M., Huhn, S. L. 2007; 107 (2): 167-172 Glutaric acidemia type I (GA-I) is a rare, autosomal recessive metabolic disorder that leads to severe dystonia, basal ganglia degeneration, and bilaterally enlarged anterior middle cranial fossae. The current management of this disease includes early diagnosis with newborn screening, prevention of catabolism, carnitine supplementation, and a strict dietary protein restriction. Neurosurgical evaluation and intervention may be necessary in patients with structural lesions associated with this disease. In this report, the authors present two pediatric patients with GA-I and discuss the neurosurgical aspects of this rare medical disorder. View details for DOI 10.3171/PED-07/08/167 Cobalamin C disease identified by expanded newborn screening: The California experience. Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) Cusmano-Ozog, K., Lorey, F., LEVINE, S., Martin, M., Nicholas, E., Packman, S., Rosenblatt, D. S., Cederbaum, S. D., Cowan, T. M., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: 24040 Early identification and aggressive treatment of cobalamin C disease. Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2007) Cusmano-Ozog, K., Martin, M., Nicholas, E., Packman, S., Rosenblatt, D. S., Cowan, T. M., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: 24950 Cobalamin c disease and expanded newborn screening: The California experience. 8th Conference of the Western Student Medical Research Forum/Western Section of the American-Federation-for-Medical-Research/Western Association-of-Physicians/Western-Society-for-Pediatric-Research/Western-Society-for-Clinical-Investigation Cusmano-Ozog, K., Lorey, F., LEVINE, S., Martin, M., Nicholas, E., Packman, S., Rosenblatt, D. S., Cowan, T. M., Enns, G. M. LIPPINCOTT WILLIAMS & WILKINS. 2007: S90S90 Systemic hyalinosis: A distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (ANTRX2) PEDIATRICS Shieh, J. T., Swidler, P., Martignetti, J. A., Ramirez, M. C., Balboni, I., Kaplan, J., Kennedy, J., Abdul-Rahman, O., Enns, G. M., Sandborg, C., Slavotinek, A., Hoyme, H. E. 2006; 118 (5): E1485-E1492 We sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.We report on 3 children who presented in infancy with symptoms and signs that initially were not recognized to be those of systemic hyalinosis. Although the children were evaluated for a variety of problems, including lysosomal storage disorders and nonaccidental trauma, all eventually underwent genetic analysis of the anthrax toxin receptor 2 gene (ANTRX2) and were diagnosed as having systemic hyalinosis.We describe the recognizable but variable clinical phenotype of systemic hyalinosis and associated mutations in ANTRX2. Affected individuals presented in early infancy with severe pain and progressive contractures. Initial diagnostic evaluations were unrevealing; however, hyperpigmented skin over bony prominences, skin nodules, and fleshy perianal masses suggested a diagnosis of systemic hyalinosis. ANTRX2 analysis confirmed the diagnosis in each case. Although 2 of the children died in infancy as a result of complications of chronic diarrhea, the third child has survived into midchildhood. These data suggest that some ANTRX2 mutations, such as that identified in the long-term survivor, may be associated with a less severe course of disease.Although some aspects of systemic hyalinosis may resemble lysosomal storage disorders, the clinical features of systemic hyalinosis are distinctive, and detection of an ANTRX2 mutation can confirm the diagnosis. Early recognition of affected individuals should allow for aggressive pain control and expectant management of the multiple associated problems, including gastrointestinal dysfunction. Immunohistochemical analysis of cytochrome oxidase deficiency using fixed tissues Vogel, H., Masek, M., Gallagher, R., Enns, G. BLACKWELL PUBLISHING. 2006: S167 Introduction to the newborn screening fact sheets PEDIATRICS Kaye, C. I., Schaefer, G. B., Bull, M. J., Enns, G. M., Gruen, J. R., Hersh, J. H., Mendelsohn, N. J., Saal, H. M., Goldberg, J. D., Hanson, J. W., Lloyd-Puryear, M. A., Rasmussen, S. A., Spire, P., Accurso, F., La Franchi, S., Lane, P. A., Northrup, H., Pang, S., Watson, M. 2006; 118 (3): 1304-1312 Newborn screening fact sheets were last revised in 1996 by the Committee on Genetics of the American Academy of Pediatrics. These fact sheets have been revised again because of advances in the field, including technologic innovations such as tandem mass spectrometry, as well as greater appreciation of ethical issues such as informed consent. The fact sheets provide information to assist pediatricians and other professionals who care for children in performing their essential role within the newborn screening public health system. The newborn screening system consists of 5 parts: (1) newborn testing; (2) follow-up of abnormal screening results to facilitate timely diagnostic testing and management; (3) diagnostic testing; (4) disease management, which requires coordination with the medical home and genetic counseling; and (5) continuous evaluation and improvement of the newborn screening system. The following disorders are reviewed in the newborn screening fact sheets (which are available at www.pediatrics.org/cgi/content/full/118/3/e934): biotinidase deficiency, congenital adrenal hyperplasia, congenital hearing loss, congenital hypothyroidism, cystic fibrosis, galactosemia,homocystinuria, maple syrup urine disease, medium-chain acyl-coenzyme A dehydrogenase deficiency, phenylketonuria, sickle cell disease and other hemoglobinopathies,and tyrosinemia. Genitopatellar syndrome: expanding the phenotype and excluding mutations in LMX1B and TBX4. American journal of medical genetics. Part A Abdul-Rahman, O. A., La, T. H., Kwan, A., Schlaubitz, S., Barsh, G. S., Enns, G. M., Hudgins, L. 2006; 140 (14): 1567-1572 Genitopatellar syndrome is a newly described disorder characterized by absent/hypoplastic patellae, lower extremity contractures, urogenital anomalies, dysmorphic features, skeletal anomalies, and agenesis of the corpus callosum. More recently, cardiac anomalies and ectodermal dysplasia have been suggested as additional features of this syndrome. We report on two additional patients with genitopatellar syndrome and expand the spectrum of anomalies to include radio-ulnar synostosis. Since there exists significant overlap in the skeletal phenotype between genitopatellar syndrome and both the nail-patella and short patella syndromes, mutation screening of their causative genes, LMX1B and TBX4, was performed. Although there still does not appear to be an identifiable molecular etiology in genitopatellar syndrome, mutations in these two candidate genes have been excluded in our patients. Since both LMX1B and TBX4 are involved in a common molecular pathway, it is likely that the causative gene of genitopatellar syndrome functions within the same developmental process. Genitopatellar syndrome: Expanding the phenotype and excluding mutations in LMX1B and TBX4 AMERICAN JOURNAL OF MEDICAL GENETICS PART A Abdul-Rahman, O. A., La, T. H., Kwan, A., Schlaubitz, S., Barsh, G. S., Enns, G. M., Hudgins, L. 2006; 140A (14): 1567-1572 Glutaryl-CoA dehydrogenase deficiency and newborn screening: Retrospective analysis of a low excretor provides further evidence that some cases may be missed MOLECULAR GENETICS AND METABOLISM Gallagher, R. C., Cowan, T. M., Goodman, S. I., Enns, G. A. 2005; 86 (3): 417-420 Glutaryl-CoA dehydrogenase deficiency (GA-I) is associated with the onset of irreversible, disabling dystonia between 3 and 18 months of age. Presymptomatic identification and treatment can prevent the devastating disability associated with this disorder. We report the retrospective analysis of the newborn blood spot of an affected child with a low excretor phenotype. The level of glutarylcarnitine was below the newborn screening program cut-off. This suggests that some cases of GA-I may be missed by newborn screening by tandem mass spectrometry. Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function (vol 386, pg 319, 2005) BIOLOGICAL CHEMISTRY Van Kuilenburg, A. B., Meinsma, R., Beke, E., Bobba, B., Boffi, P., Enns, G. M., Witt, D. R., Dobritzsch, D. 2005; 386 (10): 1075 View details for DOI 10.1515/BC.2005.123 Management of methylmalonic acidaemia by combined liver-kidney transplantation JOURNAL OF INHERITED METABOLIC DISEASE Nagarajan, S., Enns, G. M., Millan, M. T., Winter, S., Sarwal, M. M. 2005; 28 (4): 517-524 Methylmalonic acidaemia (MMA) is a rare autosomal recessive inborn error of metabolism that typically presents in infancy with recurrent episodes of metabolic acidosis, developmental delay and failure to thrive. The disease course is complicated by the development of chronic tubulointerstitial nephritis progressing to end-stage renal disease in adolescence. We describe two adolescents with cobalamin-nonresponsive MMA (mut0) who developed polyuria, chronic tubulointerstitial nephritis, dystonia but normal synthetic liver function. Both patients received combined liver-kidney transplantation (CLKT), preceded by a single pretransplant haemodialysis for clearance of methylmalonic acid. Post CLKT there was 95-97% reduction in serum and urine methylmalonic acid, leading to significant liberalization of dietary protein intake and a consequent increase in body mass index, muscle strength and energy. In addition, renal function normalized and clinical neurological status stabilized. We propose that CLKT be considered as a therapeutic option early in the course of cobalamin-nonresponsive MMA. Progressive tubulointerstitial nephritis with disabling polyuria is a confounder in patient management even in the absence of end-stage renal disease. Successful CLKT restores methylmalonyl-CoA mutase enzyme levels in the liver and kidney, improves clearance of methylmalonic acid with resultant dietary protein liberalization, and offers excellent graft and patient outcomes with improvement in quality of life. Postpartum "psychosis" in mild argininosuccinate synthetase deficiency OBSTETRICS AND GYNECOLOGY Enns, G. M., O'Brien, W. E., Kobayashi, K., Shinzawa, H., Pellegrino, J. E. 2005; 105 (5): 1244-1246 Urea cycle disorders are relatively rare but well-established causes of postpartum coma and death. Such clinical presentations have been reported previously in ornithine transcarbamylase and carbamyl phosphate synthetase deficiencies.We describe a woman, without prior symptoms of metabolic disease, who presented with hyperammonemia and psychiatric symptoms in the postpartum period. Initial diagnoses included acute fatty liver of pregnancy and postpartum psychosis. She was later found to have argininosuccinate synthetase deficiency after further metabolic investigations. Rare heterozygous mutations in the argininosuccinate synthetase gene were identified.Urea cycle disorders may present initially with postpartum psychiatric symptoms and may represent an underrecognized cause of "postpartum psychosis." We recommend obtaining metabolic studies in women with neurologic or severe psychiatric symptoms in the postpartum period. View details for DOI 10.1097/01.AOG.0000157769.90230.24 Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function BIOLOGICAL CHEMISTRY van Kuilenburg, A. B., Meinsma, R., Beke, E., Bobba, B., Boffi, P., Enns, G. M., Witt, D. R., Dobritzsch, D. 2005; 386 (4): 319-324 Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of the pyrimidine bases uracil and thymine, as well as of the widely used chemotherapeutic drug 5-fluorouracil (5FU). Analysis of the DPD gene ( DPYD ) in two patients presenting with complete DPD deficiency and the parents of an affected child showed the presence of three novel mutations, including one splice site mutation IVS11 + 1G-->T and the missense mutations 731A-->C (E244V) and 1651G-->A (A551T). The G-->T mutation in the invariant GT splice donor site flanking exon 11 (IVS11 + 1G-->T) created a cryptic splice site within exon 11. As a consequence, a 141-bp fragment encoding the aminoacid residues 400-446 of the primary sequence of the DPD protein was missing in the mature DPD mRNA. Analysis of the crystal structure of pig DPD suggested that the E244V mutation might interfere with the electron flow between NADPH and the pyrimidine binding site of DPD. The A551T point mutation might prevent binding of the prosthetic group FMN and affect folding of the DPD protein. The identification of these novel mutations in DPYD will allow the identification of patients with an increased risk of developing severe 5FU-associated toxicity. Two cases of transient 5-oxoprolinuria resolving with antioxidant therapy. Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2005) Huguenin, S. M., Gallagher, R. C., Lyons, M. J., Kwan, T., Enns, G. M., Cowan, T. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2005: 22324 Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome AMERICAN JOURNAL OF MEDICAL GENETICS PART A Currier, S. C., Lee, C. K., Chang, B. S., Bodell, A. L., Pai, G. S., Job, L., Lagae, L. G., Al-Gazali, L. I., Eyaid, W. M., Enns, G., Dobyns, W. B., Walsh, C. A. 2005; 133A (1): 53-57 Walker-Warburg syndrome (WWS) is an autosomal recessive disorder of infancy characterized by hydrocephalus, agyria, retinal dysplasia, congenital muscular dystrophy, and over migration of neurons through a disrupted pial surface resulting in leptomeningeal heterotopia. Although previous work identified mutations in the o-mannosyl transferase, POMT1, in 6 out of 30 WWS families [Beltran-Valero de Bernabe et al., 2002], the incidence of POMT1 mutations in WWS is not known. We sequenced the entire coding region of POMT1 in 30 consecutive, unselected patients with classic WWS. Two novel heterozygous mutations were found in two patients from non-consanguineous parents, whereas 28 other patients failed to show any POMT1 mutations. One patient was found to be heterozygous for a transition, g.1233T > A, which predicts p.Y352X. A second patient was found also to be heterozygous for a transition g.1790C > G, which predicts p.S537R. As an additional determination of the frequency of the POMT1 mutations in WWS, we tested for linkage of WWS to POMT1 in six consanguineous families. All six demonstrated heterozygosity and negative LOD scores at the POMT1 locus. From these data we show that POMT1 is an uncommon cause of WWS, the incidence of coding region mutations in this population of WWS being less than 7%. We conclude that while the incidence of POMT1 mutations in WWS can be as high as 20% as reported by Beltran-Valero de Bernabe et al. [2002] and it can be as low as approximately 7%, as reported here. Mild developmental delay in terminal chromosome 6p deletion AMERICAN JOURNAL OF MEDICAL GENETICS PART A Chen, K. M., Cherry, A. M., Hahn, J. S., Enns, G. M. 2004; 129A (2): 201-205 Deletions involving the short arm of chromosome 6 are relatively rare. Although features of this condition are variable, common findings include developmental delay, ocular abnormalities, hearing loss, and cardiac defects. In an effort to define further the clinical variability of this condition, we report a 6-year-old female with a de novo terminal deletion of chromosome 6 at band 6p24, with mild gross motor delays and normal cognition. Terminal 22q deletion syndrome: A newly recognized cause of speech and language disability in the autism spectrum PEDIATRICS Manning, M. A., Cassidy, S. B., Clericuzio, C., Cherry, A. M., Schwartz, S., Hudgins, L., Enns, G. M., Hoyme, H. E. 2004; 114 (2): 451-457 Cryptic subtelomeric chromosome rearrangements account for 6% to 10% of idiopathic mental retardation. As cytogenetic and molecular techniques have become more sophisticated, the number of genetic syndromes attributed to these microdeletions has increased. To date, 64 patients have been described in the literature with a more recently recognized microdeletion syndrome, del 22q13.3. The purpose of this study is to present 11 new cases of this recently described syndrome to delineate further the phenotype and to alert the clinician to another genetic condition that should be considered in the differential diagnosis of early hypotonia, delayed speech acquisition, and autistic behavior.Eleven patients were evaluated in 3 academic institutions. Clinical features and results of cytogenetic testing were recorded and tabulated. Reasons for referral for genetic evaluation included developmental delay, severe expressive speech and language delay, and dysmorphic features.Age of presentation ranged from 5 months to 46 years. There were 10 female patients and 1 male patient. All of the patients exhibited delayed motor development, some degree of hypotonia, and severe expressive speech and language delay. Dysmorphic facial features included epicanthal folds, large cupped ears, underdeveloped philtrum, loss of cupid's bow, and full supraorbital ridges. Six patients exhibited autistic-like behaviors. Microscopically visible chromosome deletions were observed in 6 patients. In the remainder, the deletion was detected with the use of fluorescence in situ hybridization.Hypotonia and developmental delay are nonspecific findings observed in many malformation and genetic syndromes. However, in association with severe speech and language delay and autistic-like behavior, this phenotype may be a significant indication to consider the 22q13 deletion syndrome as a potential cause. Head imaging abnormalities in dihydropyrimidine dehydrogenase deficiency JOURNAL OF INHERITED METABOLIC DISEASE Enns, G. M., Barkovich, A. J., van Kuilenburg, A. B., Manning, M., Sanger, T., Witt, D. R., Van Gennip, A. H. 2004; 27 (4): 513-522 Dihydropyrimidine dehydrogenase (DPD) deficiency is a rare autosomal recessive disorder of pyrimidine metabolism. Patients may present with a wide range of neurological symptoms during the first years of life. Head imaging abnormalities have been reported only rarely and include diffuse cerebral atrophy and white-matter hyperintensity. The pathogenesis of the white-matter abnormalities is unknown, although environmental factors and altered energy metabolism may be involved. To further understanding of the spectrum of brain abnormalities associated with DPD deficiency, we report a 17-month-old girl, born to a consanguineous Pakistani couple, who had a history of encephalopathy, prolonged hypoventilation, developmental delay and failure to thrive. Head MRI showed prominent sulci and abnormal T2 prolongation in the cerebral white matter and brainstem. Thus, DPD deficiency may feature prominent brain abnormalities involving the cerebral white matter and brainstem. Anoxic stress may have contributed to the clinical presentation and brain findings in this case. In order to define more clearly the contribution of DPD deficiency to the pathogenesis of these MRI abnormalities, we recommend performing detailed analysis of urine pyrimidine metabolites in patients who have such findings. Methotrexate/misoprostol embryopathy: Report of four cases resulting from failed medical abortion Bryan D Hall Festschrift 2003 Adam, M. P., Manning, M. A., Beck, A. E., Kwan, A., Enns, G. M., Clericuzio, C., Hoyme, H. E. WILEY-LISS. 2003: 7278 Methotrexate, a methyl derivative of aminopterin, is a folic acid antagonist and a known human teratogen; misoprostol is a synthetic prostaglandin E1 analog that causes uterine contractions. Recently, there has been resurgence in the use of methotrexate in combination with misoprostol or of methotrexate alone for the treatment of unwanted or ectopic pregnancies, respectively. This report documents the findings in four infants who were exposed prenatally to methotrexate alone or in combination with misoprostol in a failed attempt at medical abortion or treatment of ectopic pregnancy. All patients demonstrated growth deficiency, with growth parameters <10th centile, and all displayed features consistent with methotrexate and/or misoprostol embryopathy. Since an increasing number of medical abortions are being performed, it is important for physicians to recognize the associated teratogenic effects of these abortifacients. Data from the patients herein described should prompt obstetricians and other health care practitioners who prescribe these medications to counsel their patients regarding these risks, especially if the treatment regimen fails to induce an abortion. Compensatory amplification of mtDNA in a patient with a novel deletion/duplication and high mutant load JOURNAL OF MEDICAL GENETICS Wong, L. J., Perng, C. L., Hsu, C. H., Bai, R. K., Schelley, S., Vladutiu, G. D., Vogel, H., Enns, G. M. 2003; 40 (11) Congenital disorder of glycosylation Ic in patients of Indian origin MOLECULAR GENETICS AND METABOLISM Newell, J. W., Seo, N. S., Enns, G. M., McCraken, M., Mantovani, J. F., Freeze, H. H. 2003; 79 (3): 221-228 Congenital disorder of glycosylation type Ic (CDG-Ic) is caused by mutations in ALG6, encoding an alpha 1,3-glucosyltransferase. The most frequent mutation found in this gene (C998T resulting in an A333V substitution) has until now been found only in patients of European origin. Here we describe the first occurrence of this CDG-Ic mutation in patients of Indian origin. Of three Indian patients described in this study, patient 1 was homozygous and patient 2 heterozygous for the A333V mutation. In patient 2 we also found a new mutation, IVS3+2_3insT, just 3bp away from the previously described IVS3+5G>A substitution; both mutations resulted in exon 3 skipping. We screened a panel of >350 genomic DNA samples from an ethnically diverse American population to determine the frequency of the A333V mutation. None of the samples carried this mutation, indicating the frequency of patients carrying this homozygous mutation should be <1 in 5x10(5). The discovery of the common CDG-Ic mutation A333V in an Indian population raises questions as to its ethnic origin. View details for DOI 10.1016/S1096-7192(03)00089-1 Severe liver disease in urea cycle disorders. Western Regional Meeting of the American-Federation-for-Medical-Research Traynor, J. D., Tuchman, M., Manning, M. A., Goodman, S. I., Enns, G. M. LIPPINCOTT WILLIAMS & WILKINS. 2003: S118S118 Bilateral cystic lung disease in a monoamnionic twin of an anencephalic: A case of glial heterotopia in the lungs. Western Regional Meeting of the American-Federation-for-Medical-Research Anderson, J. M., Adams, M. L., Morgan, T., Robinson, T., Enns, G. M., Keller, K. A., Sylvester, K. G., Hintz, S. R. LIPPINCOTT WILLIAMS & WILKINS. 2003: S119S120 Clinical and molecular features of congenital disorder of glycosylation in patients with type 1 sialotransferrin pattern and diverse ethnic origins JOURNAL OF PEDIATRICS Enns, G. M., Steiner, R. D., Buist, N., Cowan, C., Leppig, K. A., McCracken, M. F., Westphal, V., Freeze, H. H., O'Brien, J. F., Jaeken, J., Matthijs, G., Behera, S., Hudgins, L. 2002; 141 (5): 695-700 To increase awareness of congenital disorders of glycosylation (CDG), we report the features of patients with a variety of clinical presentations ranging from mild hypotonia and strabismus to severe neurologic impairment.Nine North American patients with CDG type I and different ethnic origins were studied.All patients had transferrin isoelectric focusing studies with a type 1 sialotransferrin pattern. Molecular analysis showed the previously described R141H, V231M, and T237M PMM2 mutations in four patients as well as 3 rare mutations (DeltaC389, L104V, and IVS1 -1 G-->A) in the PMM2 gene in two Asian patients.The clinical features of these patients with diverse ethnic backgrounds confirm the variable course of CDG type I. Screening for CDG should be considered in children with relatively mild neurologic impairment, especially if they have suggestive findings such as cerebellar hypoplasia and abnormal fat distribution. View details for DOI 10.1067/mpd.2002.128658 Post-partum "psychosis" in mild argininosuccinate synthetase deficiency. 52nd Annual Meeting of the American-Society-of-Human-Genetics Enns, G. M., O'Brien, W. E., Kobayashi, K., Shinzawa, H., Hart, K., Gao, H. Z., Tabata, A., Saheki, T. CELL PRESS. 2002: 42525 The adolescent with an inborn error of metabolism: medical issues and transition to adulthood. Adolescent medicine (Philadelphia, Pa.) Enns, G. M., Packman, W. 2002; 13 (2): 315-? As patients with inborn errors of metabolism survive longer, understanding of potential medical and psychiatric complications adolescence and adulthood has increased. In general, detailed therapeutic guidelines for specific metabolic disorders are not available, and medical management must be tailored to the individual patient. Close interaction between the biochemical genetics clinic staff, primary care physician, mental health professional, and other specialists is necessary to formulate an integrated care plan. The education of the patient and family is a critical function of the biochemical genetics clinic, and transition from dependence on parents or other care providers to full independence is gradual. The ultimate goal is for the patient to have the essential knowledge and motivation required to cope responsibly with dietary and medical therapeutic regimens by adolescence or early adulthood. Specific illustrative inborn errors of metabolism are discussed (aminoacidemias, urea cycle defects, organic acidemias, fatty acid oxidation defects, disorders of carbohydrate metabolism, lysosomal storage disorders) in light of potential problems encountered in adolescence and adulthood, including issues involving pregnancy and long-term medical, psychosocial, and psychiatric complications. Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase and mitochondrial trifunctional protein deficiencies MOLECULAR GENETICS AND METABOLISM Hintz, S. R., Matern, D., Strauss, A., Bennett, M. J., Hoyme, H. E., Schelley, S., Kobori, J., Colby, C., Lehman, N. L., Enns, G. M. 2002; 75 (2): 120-127 Tandem mass spectrometry (MS/MS) has been introduced in several newborn screening programs for the detection of a large number of inborn errors of metabolism, including fatty acid oxidation disorders (FAOD). Early identification and treatment of FAOD have the potential to improve outcome and may be life-saving in some cases; an estimated 5% of sudden infant deaths are attributable to undiagnosed disorders of fatty acid oxidation. We report very early neonatal presentations of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (TFP) deficiencies confirmed by molecular analysis. Both patients had cardiorespiratory collapse and hypoglycemia, without a history of maternal pregnancy complications. Retrospective MS/MS analysis of the original newborn screening blood spots revealed characteristic acylcarnitine profiles. These cases are among the earliest reported presentations of LCHAD and TFP deficiencies and further illustrate the potential of MS/MS as a valuable tool for newborn screening of FAOD. However, timely analysis and reporting of results to clinicians are essential, because these disorders can manifest in the first few days of life. View details for DOI 10.1006/mgme.2001.3282 Redefining a case of Jarcho-Levin syndrome as Oculo-Auriculo-Vertebral Spectrum. Cheng, S. F., Enns, G. M., Golabi, M., Blumberg, B., Kostiner, D. R. CELL PRESS. 2001: 300300 Functional analysis of novel mutations in a congenital disorder of glycosylation Ia patient with mixed Asian ancestry MOLECULAR GENETICS AND METABOLISM Westphal, V., Enns, G. M., McCracken, M. F., Freeze, H. H. 2001; 73 (1): 71-76 Congenital disorders of glycosylation (CDG) are caused by autosomal recessive mutations in genes affecting N-glycan biosynthesis. Mutations in the PMM2 gene, which encodes the enzyme phosphomannomutase (mannose 6-phosphate <--> mannose 1-phosphate), give rise to the most common form: CDG-Ia. These patients typically present with dysmorphic features and neurological abnormalities, cerebellar hypoplasia, ataxia, hypotonia, and coagulopathy, in addition to feeding problems. However, the clinical symptoms vary greatly. The great majority of known CDG-Ia patients are of European descent where the most common mutant alleles originated. This ethnic bias can also be explained by lack of global awareness of the disorder. Here we report an Asian patient with prominent systemic features that we diagnosed with CDG-Ia resulting from two new mutations in the PMM2 gene (310C --> G resulting in L104V and an intronic mutation IVS1-1G --> A). The latter mutation seems to result in lower mRNA levels, and the L104V has been functionally analyzed in a yeast expression system together with known mutations. The Filipino and Cambodian origins of the parents show that CDG-Ia mutations occur in these ethnic groups as well as in Caucasians. Clinical course and biochemistry of sialuria JOURNAL OF INHERITED METABOLIC DISEASE Enns, G. M., Seppala, R., Musci, T. J., Weisiger, K., Ferrell, L. D., Wenger, D. A., Gahl, W. A., Packman, S. 2001; 24 (3): 328-336 Sialuria is a rare inborn error of metabolism in which excessive free sialic acid (N-acetylneuraminic acid, NeuAc) is synthesized. A defect in the feedback inhibition of UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase by the end-product of the sialic acid synthetic pathway, CMP-NeuAc, is the mechanism underlying this overproduction. Recent evidence suggests that sialuria is an autosomal dominant disorder. Only five patients have been documented to have such an enzymatic defect. We report a longitudinal study of one of the original sialuria patients, to age 11 years. Although he has coarse features and massive hepatomegaly, he has shown normal growth and relatively normal development. Pulmonary function testing showed minimal small airway obstruction. At 11 years, he developed intermittent abdominal pain and transient transaminase elevation above his baseline. Sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of a mucopolysaccharidosis or oligosaccharidosis in the absence of developmental regression or prominent dysostosis multiplex. We recommend close monitoring of liver and pulmonary function in sialuria patients. Natural history of branchio-oto-renal (BOR) syndrome. Hudgins, L., Jones, M. C., Olney, R. S., Enns, G. M., Schelley, S. L. CELL PRESS. 2000: 5656 Molecular correlations in phenylketonuria: Mutation patterns and corresponding biochemical and clinical phenotypes in a heterogeneous California population PEDIATRIC RESEARCH Enns, G. M., Martinez, D. R., Kuzmin, A. I., Koch, R., Wakeem, C. K., Woo, S. L., Eisensmith, R. C., Packman, S. 1999; 46 (5): 594-602 We studied 133 California phenylketonuria (PKU) patients and one obligate heterozygote to delineate the molecular basis of PKU in a population with greater ethnic diversity than in previous studies, and to determine whether a correlation exists between genotype and clinical phenotype, with the latter defined by both the diagnostic pretreatment blood phenylalanine (PHE) level and cognitive (IQ) test scores. To determine PAH genotypes, we used PCR-mediated amplification, denaturing gradient gel electrophoresis, and direct sequencing on dried whole blood samples. Where possible, mutation severity was defined according to predicted in vitro PAH enzyme activity estimated by using Cos cell expression analysis for a given mutation. We then asked whether mutation severity, as defined by such expression analysis, correlated with pretreatment PHE levels or with IQ test results. A mutation was identified in 236 (88%) of 267 mutant alleles. Seventeen new mutant alleles were found; A47E, T81P, I102T, E182G, T328D, Y343P, K371R, Y387H, A389E, E422K, IVS9nt5, IVS11nt20, delS70, del364-368/del198-220, delF299, delT323, and -1C/T. In striking contrast to a number of studies in other populations, in this study, based on predicted PAH activity, we observed no correlation between mutation severity and pretreatment PHE levels. There was also no correlation between genotype and IQ. We conclude that in samples collected from an ethnically heterogeneous population, there is no correlation of mutation severity with either pretreatment PHE levels or IQ measurement in treated patients. We caution that genetic counseling in PKU should incorporate the notion that prognosis may not be predicted with precision based on mutation analysis in a given patient. Apparent cyclophosphamide (cytoxan) embryopathy: A distinct phenotype? AMERICAN JOURNAL OF MEDICAL GENETICS Enns, G. M., Roeder, E., Chan, R. T., Catts, Z. A., Cox, V. A., Golabi, M. 1999; 86 (3): 237-241 Cyclophosphamide (CP) is an alkylating agent widely used in treating cancer and autoimmune disease. CP is classified as a pregnancy risk factor D drug and is teratogenic in animals, but population studies have not conclusively demonstrated teratogenicity in humans. Six isolated reports of prenatally exposed infants with various congenital anomalies exist, but to date no specific phenotype has been delineated. The purpose of this report is to document a new case of in utero CP exposure with multiple congenital anomalies and to establish an apparent CP embryopathy phenotype. The mother had systemic lupus erythematosus and cyclophosphamide exposure in the first trimester. She also took nifedipine, atenolol, clonidine, prednisone, aspirin, and potassium chloride throughout pregnancy. The infant had growth retardation and multiple anomalies including microbrachycephaly, coronal craniosynostosis, hypotelorism, shallow orbits, proptosis, blepharophimosis, small, abnormal ears, unilateral preauricular pit, broad, flat nasal bridge, microstomia, high-arched palate, micrognathia, preaxial upper limb and postaxial lower limb defects consisting of hypoplastic thumbs, and bilateral absence of the 4th and 5th toes. Chromosomes were apparently normal. The reported cases of in utero exposure to cyclosposphamide shared the following manifestations with our patient: growth deficiency, developmental delay, craniosynostosis, blepharophimosis, flat nasal bridge, abnormal ears, and distal limb defects including hypoplastic thumbs and oligodactyly. We conclude that (a) cyclophosphamide is a human teratogen, (b) a distinct phenotype exists, and (c) the safety of CP in pregnancy is in serious question. Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin JOURNAL OF INHERITED METABOLIC DISEASE Enns, G. M., Barkovich, A. J., Rosenblatt, D. S., Fredrick, D. R., Weisiger, K., Ohnstad, C., Packman, S. 1999; 22 (5): 599-607 Cobalamin C (cblC) defects result in decreased activity of both methylmalonyl-CoA mutase and N5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase), with subsequent methylmalonic acid-uria and homocystinuria. Patients typically show failure to thrive, developmental delay and megaloblastic anaemia. Vitamin B12 therapy has been beneficial in some cases. We report a now 4-year-old Hispanic girl with cblC disease documented by complementation analysis, with progressive neurological deterioration and worsening head MRI changes while on intramuscular hydroxocobalamin begun at age 3 weeks. Oral carnitine and folic acid were added at age 1 year. Blood levels of methylmalonic acid were reduced to treatment ranges. In the absence of acute metabolic crises, she developed microcephaly, progressive hypotonia and decreased interactiveness. Funduscopic examination was normal at age 13 months. At age 19 months, she developed nystagmus, and darkly pigmented fundi and sclerotic retinal vessels were observed on examination. Her neonatal head MRI was normal. By age 1 year, the MRI showed diffuse white-matter loss with secondary third and lateral ventricle enlargement, a thin corpus callosum, and normal basal ganglia. At age 15 months, progression of the white-matter loss, as well as hyperintense globi pallidi, were present. Interval progression of both grey- and white-matter loss was seen at age 27 months. We therefore caution that progressive neurological deterioration and head MRI abnormalities may still occur in cblC disease, despite early initiation of hydroxocobalamin therapy and improvement in toxic metabolite concentrations in physiological fluids. Severe congenital anomalies requiring transplantation in children with Kabuki syndrome AMERICAN JOURNAL OF MEDICAL GENETICS Ewart-Toland, A., Enns, G. M., Cox, V. A., Mohan, G. C., Rosenthal, P., Golabi, M. 1998; 80 (4): 362-367 Kabuki syndrome (KS) is a rare multiple malformation disorder characterized by developmental delay, distinct facial anomalies, congenital heart defects, limb and skeletal anomalies, and short stature. Renal anomalies have been reported in a few cases of KS, but to our knowledge, hepatic anomalies have not. Here, we document two cases of KS requiring liver or kidney transplantation: one with severe hepatic and renal anomalies and one with severe renal anomalies. Both cases had the characteristic facial appearance of children with KS, postnatal growth deficiency, and developmental delay. At birth, case 1 presented with hypoglycemia, ileal perforation, right hydroureter, and hydronephrosis. The patient subsequently developed hyperbilirubinemia, hepatic abscess, and cholangitis. At age 8 months, he underwent a liver transplant. Hepatic pathology diagnosed neonatal sclerosing cholangitis. Case 2 presented with renal failure at age 6 years. Renal ultrasound study showed markedly dysplastic kidneys requiring transplantation. In addition to characteristic findings of KS, she had coronal synostosis and was shown to have immune deficiency and an autoimmune disorder manifesting as Hashimoto thyroiditis and vitiligo. We conclude: 1) severe hepatic and renal anomalies leading to organ failure can occur in KS; 2) patients with neonatal sclerosing cholangitis should be examined closely for features of KS; 3) coronal synostosis may occur in KS; and 4) immune deficiency and autoimmune disorder can be associated with KS. View details for PubMedID 9856564 Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: A retrospective study of 60 patients and literature review AMERICAN JOURNAL OF MEDICAL GENETICS Enns, G. M., Cox, V. A., Goldstein, R. B., Gibbs, D. L., Harrison, M. R., Golabi, M. 1998; 79 (3): 215-225 Congenital diaphragmatic defects (CDDs) may occur in malformation syndromes of varied causes. Syndromic cases of CDDs due to chromosomal defects, autosomal recessive, autosomal dominant, or X-linked inheritance have been described. In order to determine the frequency and nature of syndromes, malformations, and chromosome abnormalities associated with CDDs, we reviewed the records of all patients with CDDs evaluated over a 4-year period. During the 4-year interval, a total of 60 patients was evaluated. Of these, 29 had a therapeutic or spontaneous abortion, and 31 received postnatal care. On prenatal ultrasonography, 20 of 60 (33%) of patients with CDDs had additional anomalies. Additional anomalies, besides CDDs, were present in 15 of 31 (48%) of liveborn patients on newborn evaluation. In total, 16 patients with multiple anomalies were evaluated. Of these, 12 of 16 (75%) had additional abnormalities detected by prenatal ultrasonography. The 4 of 16 (25%) without additional anomalies on prenatal sonography had multiple anomalies found neonatally, lethal multiple pterygium syndrome being diagnosed in one case. Prenatal chromosome analysis was performed in 7 of 16 patients, and all had postnatal karyotypes. All initial karyotypes were normal. Tetrasomy 12p was documented on postnatal fibroblast analysis in one case who had percutaneous umbilical blood sampling (PUBS). Syndromes diagnosed postnatally in 7 of 16 patients (44%) include: Fryns syndrome (2), Simpson-Golabi-Behmel syndrome (2), tetrasomy 12p (1), Brachmann-de Lange syndrome (1), and lethal multiple pterygium syndrome (1). We were unable to make a specific diagnosis in 9 of 16 patients (56%) with multiple malformations. In patients with CDDs, a normal prenatal karyotype, especially if obtained by PUBS, and absence of other detected abnormalities by fetal ultrasonography, do not exclude the presence of other major anomalies, including chromosome abnormalities and severe multiple malformation syndromes.	cc/2019-30/en_head_0044.json.gz/line3311
__label__cc	0.612857	0.387143	Read this page in: The single-minded focus on getting Washington on board at the UN climate conference in Bali resulted in the lack of firm targets for reducing emissions. (Bali, Dec. 16). A day after the dramatic ending of the Bali climate talks, many are wondering if the result was indeed best outcome possible given the circumstances. The US was brought back to the fold, but at the cost of excising from the final document--the so-called Bali Roadmap--any reference to the need for a 25 to 40 per cent reduction in greenhouse gas emissions from 1990 levels by 2020 to keep the mean global temperature increase to 2.0 to 2.4 degrees Celsius in the 21st century. Reference to quantitative figures was reduced to a footnote referring readers to some pages in the Intergovernmental Panel on Climate Change (IPCC) 2007 Report which simply enumerates several climate stabilization scenarios. The alternative scenarios ranged from a 2.0 to 2.4 degree rise in temperature to a 4.9 to 6.1 degree increase. This prompted one civil society participant to remark that "The Bali roadmap is a roadmap to anywhere." Would it have been better to have simply let the US walk out, allowing the rest of the world to forge a strong agreement containing deep mandatory cuts in greenhouse gas emissions on the part of the developed countries? With a new US president with a new policy on climate change expected at the beginning of 2009, the US would have rejoined a process that would already be moving along with strong binding targets. As it is now, having been part of the Bali consensus, Bush administration negotiators, say skeptics, will be able to continue their obstructionist tactics to further water down global action throughout the negotiations in 2008. One wonders what would have happened had Washington remained true to its ideological propensities and decided to stomp out of the room when the delegate from Papua New Guinea, releasing the conference’s pent up collective frustration, issued his now historic challenge: "We ask for your leadership and we seek your leadership. If you are not willing to lead, please get out of the way." As everyone now knows, after last-minute consultations with Washington, the American negotiator backed down from the US’s hard-line position on an Indian amendment seeking the conference’s understanding for the different capacities of developing countries to deal with climate change and said Washington "will go forward and join the consensus." The single-minded focus on getting Washington on board resulted in the dearth of hard obligations agreed upon at the meeting except for the deadline for the negotiating body, the "Ad Hoc Working Group on Long-term Cooperative Action under the Convention," to have its work ready for adoption at the Conference of Parties in Copenhagen in 2009 (COP 15). Many delegates also felt ambivalent about the institutional arrangements that were agreed upon after over a week of hard North-South negotiations. An Adaptation Fund was set up, but it was put under the administration of the Global Environmental Facility (GEF) of the US-dominated World Bank. Moreover, the seed funds from the developed countries are expected to come to only between $18.6 million to US$37.2 million--sums which are deemed severely inadequate to support the emergency efforts to address the ongoing ravages of climate change in the small island states and others on the "frontlines" of climate change. Oxfam estimates that a minimum of US$50 billion a year will be needed to assist all developing countries adapt to climate change. A "strategic program" for technology development and transfer was also approved, again with troubling compromises. The developing countries had initially held out for the mechanism to be a designated a "facility" but finally had to agree to the watered-down characterization of the initiative as a "program" on account of US intransigence. Moreover, the program was also placed under the GEF with no firm levels of funding stated for an enterprise that is expected to cost hundreds of billions of dollars. The REDD (Reducing Emissions from Deforestation and Degradation) initiative pushed by host Indonesia and several other developing countries with large forests that are being cut down rapidly was adopted. The idea is to get the developed world to channel money to these countries, via aid or market mechanisms, to maintain these forests as carbon sinks. However, many climate activists fear that indigenous communities will lose be victimized by predatory private interests that will position themselves to become the main recipients of the funds raised. Still, many felt that the meager and mixed results were better than nothing. Perhaps the best indication on whether the conference was right to bend over backward almost 180 degrees to accommodate the US will come next month in Honolulu during the Major Economies Meeting, a Washington-initiated conference that was originally designed to subvert the United Nations process. The question on everyone's lips is: Will the Bush adminstration revert to form and use the conference to launch a separate process to derail the Bali Roadmap? Walden Bello, a fellow of the Transnational Institute, is senior analyst at Focus on the Global South and professor of sociology at the University of the Philippines. He was an NGO participant at the Bali Conference on Climate Change.	cc/2019-30/en_head_0044.json.gz/line3315
__label__cc	0.663818	0.336182	Cochlear Implants: How Are They Different from He... Cochlear Implants: How Are They Different from Hearing Aids? Posted June 15, 2017 by Maria E. Pomponio, AuD, CCC-A, FAAA, Sarah Sohns, AuD What Is a Hearing Aid? A hearing aid is a small electronic device that makes some sounds louder for a person with hearing loss. Hearing aids are typically worn one of two ways: either completely in the ear, or with parts inside of and behind the ear. They can help people in both quiet and noisy environments so they can listen and communicate better. Hearing aids are often used to improve hearing and speech understanding for people with a kind of hearing loss called “sensory-neural hearing loss.” This kind of hearing loss is caused when the nerve cells in the inner ear, called hair cells, are damaged. The more damage is done to a person’s hair cells, the more severe the hearing loss becomes. Individuals with severe hearing loss need a lot more power from the hearing aid for it to help them. If the hair cells are too damaged, hearing aids may provide little to no help to the user when it comes to understanding speech. So, what’s the next step after a hearing aid does not help a person with a severe to profound hearing loss? That person may be a candidate for a cochlear implant. How Is a Cochlear Implant Different from a Hearing Aid? In order to better understand the differences between a hearing aid and a cochlear implant, it is important to understand how each one works. A hearing aid has three basic parts: the microphone, amplifier, and speaker. Sound goes into a hearing aid through its microphone. When the sound is in there, the amplifier makes sound louder. Then, that sound is sent to the inner ear (a part of the ear you cannot see when you look at someone) through speaker. Once the sound gets to a person’s inner ear, the hair cells in that area send the sound to the hearing (auditory) nerve. This nerve sends the sound signal on to the brain. The brain makes sense of that signal so a person can understand it. When a person has a hearing loss, the hair cells that send the signal from one spot to another become damaged. When they become damaged, the signal that they send to the brain becomes unclear. When the brain gets a signal that is not clear, it is hard for that person to understand speech, even though the sounds are loud enough to hear. Words may sound garbled to the person with hearing loss. A cochlear implant replaces the job of the hair cells. Instead of the (damaged) hair cells sending sounds to the hearing nerve and on to the brain, a cochlear implant uses a few electrodes, or tiny metal contacts, that send electrical signals to the hearing nerve and on to the brain. That way, the hair cells are not used at all. But for us to use a cochlear implant, the implant has to be able to change sound into an electrical signal. Otherwise, the electrodes will not help us. Cochlear implants have several parts that allow this to happen. When we talk about a cochlear implant, we are actually talking about a device with multiple parts. There are external (outside) parts to the implant (called the “microphone,” “sound processor,” and “transmitter”), and internal (inside) parts to the implant (called the “receiver-stimulator” and the “electrode array”). Sounds are collected and changed by the outside parts and sent to the inside parts. Remember, sound has to change into electrical signals so that when it reaches the electrodes, they can pass these signals on to the brain. This process is described here: Microphone: Picks up sound from the environment and sends it to the sound processor. Sound Processor: Changes the signal picked up by the microphone into a digital code, which is then sent to the transmitter. Transmitter: Sends the digital code from the processor to one of the inside parts, the receiver-stimulator. Receiver-Stimulator: Is surgically placed under the person's scalp. It changes the digital signal from the transmitter into electrical signals that are sent to the electrode array. Electrode Array: Is surgically implanted into a part of the inner ear known as the cochlea. The electrodes send the electrical signals to the hearing nerve, which sends those signals to the brain. The outside parts of a cochlear implant usually look like a hearing aid and sit behind the person’s ear. Unlike a hearing aid, the part that sits behind the ear is connected to something else: a magnet. That magnet sits on the person’s scalp. It attaches to the magnet of the receiver-stimulator (one of the inside parts to the implant): This is the part where the outside part of the device connects to the inside part of the device. Thanks to new technology, not all cochlear implants need to be worn behind the ear. Now, certain cochlear implants can be worn just on the scalp, with nothing on a person’s ear! Related Post: “Cochlear Implants: Am I A Candidate?" Maria E. Pomponio, AuD, CCC-A, FAAA Maria E. Pomponio, AuD, CCC-A, FAAA is an Audiologist at the Temple Head and Neck Institute and an Instructor of Clinical Otolaryngology/Head and Neck Surgery at the Lewis Katz School of Medicine at Temple University. Maria specializes in newborn hearing screenings, pediatric diagnostic assessment, the evaluation and management of central auditory processing disorders in adults and children, electrophysiology, vestibular evaluations, and ototoxic monitoring. See all posts from Maria E. Pomponio, AuD, CCC-A, FAAA Sarah Sohns, AuD Sarah Sohns, AuD, is an Audiologist at the Temple Head & Neck Institute and an Instructor of Clinical Otolaryngology/Head and Neck Surgery at the Lewis Katz School of Medicine at Temple University. Sarah specializes in auditory-evoked responses, matching amplification technology to patient needs using evidence-based practice, tinnitus evaluation and management, validation of hearing aid fittings, and ototoxicity. See all posts from Sarah Sohns, AuD	cc/2019-30/en_head_0044.json.gz/line3317
__label__wiki	0.977586	0.977586	Designers share plans for new Carter House Visitor Center The design team shared their plans with the Historic Zoning Commission's design review committee. Designers share plans for new Carter House Visitor Center The design team shared their plans with the Historic Zoning Commission's design review committee. Check out this story on Tennessean.com: https://www.tennessean.com/story/news/local/williamson/2018/03/19/designers-head-toward-final-plans-new-carter-house-visitor-center/439843002/ Emily R. West, USA TODAY NETWORK - Tennessee Published 5:56 p.m. CT March 19, 2018 \| Updated 7:29 p.m. CT March 19, 2018 What you need to know about the historic Carnton site. Wochit Carter House in Franklin.(Photo: Steven S. Harman, Steven S. Harman) Architects moved forward Monday with new steps to create the new Carter House Visitor Center. The design team shared their plans with the Historic Zoning Commission's design review committee, a nonbinding monthly meeting that gives developers an opportunity for feedback prior to submitting their plans. State lawmakers allocated $3.2 million in the 2017-2018 budget for the new center. The Battle of Franklin Trust — which oversees both the Carnton and Carter House sites —has hoped for a new center since it released its master plan for the Carter House campus in 2015. Central to the Battle of Franklin, the Carter family hid in their basement while the war waged outside on their front yard. More: Battle of Franklin site upgrade is "certain," official says More: 5 things to know about the Battle of Franklin Proposed architecture of the new building will draw off an agricultural feel, designers said. It also will mirror the visitor center on its sister campus at Carnton. Plans for the new center call for a two-story structure. Visitors enter into the lower level, and on the lower level will sit the museum and orientation center. It will also include offices, a gift shop and restrooms. The Carter House State Historic Site master plan is shown above. (Photo: Submitted) "It was important that visually things be open and that you look out onto the lawn to the Carter House," visitor center architectural planner Baird Dixon said. "It will hopefully be an open feel when you arrive into the building." The second floor of the building will offices, storage, a multipurpose room and restrooms. More: On the trench line: New federal cannons on site at Franklin battlefield "They really need more office space because they are so cramped at Carnton," he said. "This will give them relief. It will also allow for conference and outside groups to use the building." The Historic Zoning Commission will have to approve the the demolition of the current building and approve the construction of the new center. Prior to the build, the state will do archaeological investigations as part of the project. Around 40,000 visitors come to the site annually. Master plans for Carter House For the last three years, historians and preservationists have chipped away at their master plan for the Tennessee historic site. For the first time in 173 years, the farm office of the Carter House opened in 2017 as a piece of the tour of the home and the grounds. The north and south walls of the building remain exposed, showing the intense damage that occurred during the Battle of Franklin. More: Franklin's Carter family farm office opened for the first time since damaged in Civil War In spring 2016, the Battle of Franklin Trust had the former Franklin High School gym demolished. Originally in 2007, plans had been made to make the old gym into the new visitor's center. At the time, around the state gave $1.2 million for renovation work. But after sitting for an additional nine years and deterioration, an updated analysis of the building showed it would more to fix the old gym than building the new one. About the Battle of Franklin The Battle of Franklin was one of the bloodiest battles in the western theater. The outcome of the battle changed the outlook on the Civil War. The Confederacy and the Union suffered 10,000 causalities in the fight. To commemorate the grounds, preservationists have been working more than a decade to buy back pieces of the battlefield. Groups like Franklin's Charge, the Heritage Foundation of Williamson County, the Battle of Franklin Trust and Save the Franklin Battlefield have helped raise $19 million to create Carter Hill Battlefield Park. About Carter Hill Battlefield Park Adopted in the City of Franklin Park system in 2016, Carter Hill Battlefield Park is situated on both sides Columbia Avenue, complimenting the house site. The park is now open space, but once had a Domino's Pizza and Pizza Hut using the land. It also had houses on different parcels of the land that eventually made up the parkland. Carter Hill Battlefield Park came out of the efforts of Franklin's Charge and the American Battlefield Protection Act project, which has now provided $1.7 million to help preserve the land. Reach Emily West at erwest@tennessean.com; at 615-613-1380; or on Twitter at @emwest22. Read or Share this story: https://www.tennessean.com/story/news/local/williamson/2018/03/19/designers-head-toward-final-plans-new-carter-house-visitor-center/439843002/ Nashville police officer arrested on domestic assault charge in Cheatham First Cracker Barrel moved to Wilson County fairgrounds House Speaker Glen Casada claims he can no longer pay alimony Electric scooters will stay in Nashville — for now	cc/2019-30/en_head_0044.json.gz/line3318
__label__wiki	0.960446	0.960446	On growth, diversity, immigration and trade, UT/TT Poll finds two states of Texas Texas is growing and becoming much more ethnically and racially diverse. Texas voters differ as to whether those are positive or negative trends, according to the latest University of Texas/Texas Tribune Poll. by Ross Ramsey June 18, 2019 12 AM Illustration by Emily Albracht/The Texas Tribune For all of the boasting from business and political leaders about how fast the state is growing, many Texas voters have their concerns about whether getting bigger or more diverse is a good thing, according to the latest University of Texas/Texas Tribune Poll. And on that and other questions, their differences often match their party preferences. While 39% of voters think the state’s population growth is good for the state, 34% think it’s bad for Texas and 27% don’t have an opinion on that question. And on balance, Republicans have more misgivings than Democrats, the poll found. Among Democratic voters, 47% said the state’s growth has been good for Texas, and 23% percent said it has been bad. Among Republicans, the numbers flip, with 34% praising the growth and 43% saying growth has been bad for the state. But party wasn’t the only difference. Among women, 35% were pro-growth, and 34% think it’s bad for the state. Men were more likely to say growth was good (45%) than bad (34%). Republican women were notably skeptical, with 28% saying growth has been good for the state and 46% saying it’s been bad. “Women are more likely to say they’re unsure,” said Joshua Blank, manager of polling and research for the Texas Politics Project at the University of Texas at Austin. Nearly a third (31%) of women said they don’t have an opinion, compared to 23% of men. The state’s increasing racial and ethnic diversity is a cause for optimism, according to 44% of the voters — and a cause for pessimism, according to 33%. Again, it depends on who is talking, and the partisan differences are strong: 67% of Democrats said rising diversity is a cause for optimism; among Republicans, 28% agreed with that, while 44% said the state’s increasing ethnic and racial diversity is cause for concern. Independent voters were split on the question: 33% optimistic, 36% pessimistic. Trump, trade and tariffs Overall, more Texas voters than not approve of President Donald Trump’s handling of economic, trade and foreign affairs, but only on his handling of the economy does that support come from more than half of the voters. Approval and disapproval of his policies appear relatively close, though more voters approve of the president’s work than disapprove. But the overall numbers cloak big partisan differences. His numbers on handling of the economy are driven by strong support among Republicans, 90% of whom gave the president good marks. Among Democrats, only 11% approve of Trump’s economic record, while 76% do not. That Republican support runs through approving responses to the president’s handling of trade negotiations (81%), immigration and border security (85%), foreign relations (83%) and taxes (84%). Democrats couldn’t disagree more, disapproving — with equivalent intensity — of Trump’s handling of trade negotiations (86%), immigration and border security (86%), foreign relations (85%) and taxes (82%). Trump’s proposal to put a tariff on goods imported from Mexico won approval from Republicans (74%) and disapproval from Democrats (76%). Overall, Texas voters were split 43% to 42% on that question. That tariff proposal — which was settled after pushback from Republican leaders and others inside and outside of Congress — would have been bad for the Texas economy, according to 49% of Texas voters. And Republican voters split evenly, with 27% saying it would hurt the economy and the same number saying it would be good for Texas. Only 8% of Democrats and 17% of independent voters said tariffs would help the economy, while 76% of Democrats and 46% of independents said it would hurt. The Republican sentiment revealed in the poll illustrates a dilemma that faced GOP policymakers, who were caught between their voters’ current support for tariffs and those voters’ concerns about the economic effects, said James Henson, who runs the Texas Politics Project at the University of Texas at Austin and co-directs the poll. “In this particular circumstance, the linkage of immigration and trade and the Mexico thing reveals how people don’t have well-developed, deeply rooted attitudes about trade,” Henson said. “This is why the Republican elites were panicked about the trade thing. They couldn’t fight it on the front end, and they were going to have to pay for it on the back end.” But even with those misgivings from voters, many Texans believe tariffs would be effective “at making the Mexican government do more to prevent migrants from coming to the United States.” In spite of their other reservations, 70% of Republicans said they support that sentiment. Among Democrats, 13% said tariffs would be effective, and 28% of independent voters agreed with that assessment. The University of Texas/Texas Tribune internet survey of 1,200 registered voters was conducted from May 31-June 9 and has an overall margin of error of +/- 2.83 percentage points. Numbers in charts might not add up to 100% because of rounding. Disclosure: The University of Texas at Austin has been a financial supporter of The Texas Tribune, a nonprofit, nonpartisan news organization that is funded in part by donations from members, foundations and corporate sponsors. Financial supporters play no role in the Tribune's journalism. Find a complete list of them here. Trump’s reelection support is 50-50 in Texas, Biden and O’Rourke lead the Democrats, UT/TT Poll says Texans approve of Trump’s job performance but have questions about his character, UT/TT Poll says Beto O’Rourke touts his immigration credentials. But these El Pasoans say he doomed their historic migrant neighborhood. University of Texas/Texas Tribune Poll, June 2019 — Summary, Day 2 (151.5 KB) DOWNLOAD University of Texas/Texas Tribune Poll, June 2019 — Methodology (63.5 KB) DOWNLOAD	cc/2019-30/en_head_0044.json.gz/line3319
__label__cc	0.616824	0.383176	Plan to Prevent Pneumococcal Disease Testimony by Marilyn M. Doyle, MD House Public Health Testimony on House Bill 970 by Rep. Philip Cortez Chairman Price and members of the committee, the Texas Medical Association appreciates the opportunity to present comments on behalf of our more than 50,000 members in support of House Bill 970. I’m Dr. Marilyn Doyle, and I’m a general pediatrician and an assistant professor of medicine at Dell Medical School. I support the pediatric residency program at Dell Medical School and care for patients at the East Austin CommUnityCare clinic here in Austin. We are pleased that Representative Cortez is again proposing the development of a state plan to prevent and treat Streptococcus pneumoniae in Texas. S. pneumoniae has been a leading contributor to illness and death in some populations in Texas. It can cause pneumococcal disease, which includes pneumococcal pneumonia, meningitis, and sepsis. Each of these can lead to acute illness requiring hospitalization and can result in disability and even death. Texas represents a substantial proportion of the more than 400,000 annual cases of pneumococcal disease in the United States. And while pneumococcal disease is a very serious risk for our aging population, many people don’t realize it also can cause severe illness in the patients I care for — those under the age of 6, and other children whose health conditions make them more vulnerable to serious infections. But we can prevent most cases of pneumococcal disease with timely vaccination of young children, adults age 65 and older, and children and adults of any age with weakened immune systems. Each adult 65 years and over should be vaccinated routinely for pneumococcal disease. While most adults in this age group are Medicare-insured and should have access to vaccination, perhaps 25 percent or more are not vaccinated. Both in Texas and in the United States, the 2015 vaccination rate for the pneumococcal vaccine averaged about 70-72 percent for those in the 65-and-older age group. We do better in vaccinating young children in Texas against this disease, with 83 percent of children receiving the recommended pneumococcal vaccine dosage (2015); the national average is slightly higher at 84 percent (NIS Vaccination Coverage Levels in Texas and U.S.). But most importantly, I can assure you: Improving the vaccination rate of young children for pneumococcal disease is resulting in decreasing disease and death in young children. We hope that one of the outcomes of developing a state prevention plan will be to learn why more of our elderly adults and vulnerable young children are not fully vaccinated, and to identify areas of the state with low vaccination rates. Unfortunately, we have limited information on the vaccination of adults, so it’s essential we learn more about those who are at risk of severe illness from exposure to S. pneumoniae. This includes adolescents and adults younger than age 65 with chronic conditions like asthma or kidney disease, diabetes, or cancer or a cardiac condition. We must identify ways to ensure this population knows about the benefits of vaccination — particularly if they are uninsured. We are alarmed at the potential funding reductions in our state’s Adult Safety Net vaccination program, which could result in uninsured adults having less access to vaccination. While Texas needs a complete state prevention plan for S. pneumoniae, we recognize that a collaboration of stakeholders now could bring immediate benefit. By gathering advocates, consumers, organizations, and individuals, we can begin identifying community-based and state vaccination and education resources, the educational needs of the target population, and clinical resources and developments. Texas’ large and diverse population presents a unique opportunity to bring together a diverse group to help develop prevention strategies for those who most need support to avoid becoming ill from pneumococcal disease. We thank Representative Cortez for bringing HB 970 forward for your consideration, and we look forward to the opportunity to work with you on its implementation. Immunization \| Public Health \| Texas immunization \| Texas legislation Measles Update: 17 Cases in 12 Texas Counties in 2019 Public health officials are investigating two reported cases of measles in El Paso, bringing the state's total to 17 cases since the beginning of 2019. Read More	cc/2019-30/en_head_0044.json.gz/line3320
__label__wiki	0.863764	0.863764	Parasitologist, Reprogrammed: A Profile of David Roos After discovering a novel organelle found in protozoan parasites, the University of Pennsylvania’s Roos created a widely used eukaryotic pathogen database. Anna Azvolinsky DAVID ROOS E. Otis Kendall Professor of Biology, University of Pennsylvania Director, Penn Genomics Institute, 2001 to 2006COURTESY OF DAVID ROOS David Roos had been studying nucleated parasites such as Toxoplasma and Plasmodium (malaria) for several years when he decided to ask a simple question: How do antibiotics such as clindamycin work in treating both malaria and toxoplasmosis? The answer turned out to be a discovery that simultaneously solved three biological mysteries, rewrote biology textbooks, and helped to launch the field of evolutionary cell biology. Clindamycin and related drugs kill bacteria by inhibiting the ability of bacterial ribosomes to synthesize proteins, but don’t affect ribosomes in eukaryotic cells, including those of humans. Yet both malaria and toxoplasmosis are caused by eukaryotic unicellular parasites, which clindamycin also treats. In 1996, Roos, a professor of biology at the University of Pennsylvania, and then-graduate student Maria Fichera tested three possible hypotheses: clindamycin does indeed inhibit protein synthesis in Toxoplasma enough to prevent disease but somehow fails to kill the parasite; the drug kills Toxoplasma by some other mechanism; or the antibiotic targets the parasite’s mitochondrial but not cytoplasmic ribosomes. After several months of experiments, none of these models could explain the antibiotic’s parasite-fighting abilities. I want to create tools that allow other users to ask their own questions, rather than my being the ‘big computer scientist’ who does the analysis and then tells others an answer. A fourth, “crazier” idea, according to Roos, was that the parasites that cause toxoplasmosis and malaria harbor yet another type of undiscovered ribosome targeted by the antibiotic. The idea, says Roos, was inspired by prior reports of ribosomal genes on small circular DNA that was mistakenly assumed to have come from the parasites’ mitochondria. The experiments to test this wild hypothesis ended up resolving three mysteries in parasite biology: why some antibiotics are effective against protozoan parasites; the source and function of the circular DNA originally observed in the 1970s in Toxoplasma and other eukaryotic parasites; and the identity of an uncharacterized organelle-like structure with multiple membranes. In two back-to-back papers in Science and Nature in 1997, Roos, then-postoc Sabine Köhler, and Fichera established that clindamycin and a few other antibiotics target ribosomes encoded by these novel DNAs found in the parasites and that these sequences are associated with a distinctive organelle surrounded by four membranes. They dubbed the newly discovered organelle the apicoplast. The organelle was acquired, evolutionarily speaking, when an ancestral parasite “ate” a eukaryotic alga that already harbored a plastid through the endosymbiosis of a free-living cyanobacterium. Unlike plant and algal plastids, the team showed, the apicoplast had lost the ability to photosynthesize, but the organelle was essential for the parasite, including for protein synthesis. The acquisition of apicoplasts by certain parasites studied by the team was the first proven example of secondary endosymbiosis—a “nesting dolls” phenomenon in which a eukaryotic cell swallows another eukaryote, which itself had a prokaryotic cell already residing in it. For Roos, the story highlights the “remarkable cell biological and evolutionary insights that can be gleaned only by studying eukaryotic diversity.” An early computer programming start Although Roos made a name for himself when the discovery of the apicoplast made it into textbooks, biology was not his initial career ambition. He enjoyed the natural world growing up—hiking, skiing, and exploring the mountains and forests around his hometown—but his interest in computers also had an early start. Born in 1956 in Boston, Massachusetts, Roos was raised in Hanover, New Hampshire, his father a biology professor at Dartmouth College. Roos’s elementary school participated in an innovative pilot program initiated by Dartmouth’s John Kemeny, a computer scientist who co-invented BASIC, one of the most widely used computer languages worldwide. Kemeny had a vision that computers should be accessible tools for everyone, and Roos, along with his second-grade classmates, was taught how to program. “This was visionary in the 1960s when computers were seen as tools for computer scientists that would benefit the public indirectly,” says Roos. “Most people didn’t think that computers would be something everyone would use in their daily lives.” Roos continued to program through high school but also had many other interests, including art and math. During that time, he took college math classes at Dartmouth, and when he applied for college his senior year in 1973, Roos was “shocked to discover the backwards computer science technology at both MIT and Stanford” compared to what he was used to at Dartmouth. “I visited MIT, and they told us with great pride how they could have twenty users time-sharing their computers, when at Dartmouth, we had ten times that many computer users at the same time.” Dismayed, Roos decided to enter the workforce instead, becoming a computer programmer for the computer company Honeywell. After a year and half on the job, he applied to colleges, entering Harvard University in 1975. First art, then science Initially, Roos was an art major, taking both studio art classes and art history. “It’s a pet peeve of mine that some find a contradiction between interest in art and science. I find that science is a very aesthetically pleasing and artistically driven discipline in many respects,” he says. Eventually, though, biology won out. Roos was singled out by a biology teaching assistant who suggested he approach Morris Karnovsky, a cell biologist and morphologist, about working in his lab. Roos accepted the nudge, and in Karnovsky’s lab he researched how cell membranes change during polyethylene glycol (PEG)–induced cell fusion. He also characterized the membranes of mammalian cell lines he had isolated that could resist PEG-induced fusion in Richard Davidson’s lab, then at Children’s Hospital Medical Center in Boston. These hands-on experiences made Roos switch his major to biology and also apply to graduate school. Initially, Roos applied to MD/PhD programs, but the admission committees gave him a hard time, he recalls, questioning his commitment to the field based on his prior meanderings in computer science and art. Even though he thought he was only interested in MD/PhD programs, on a whim Roos accepted an invitation from Rockefeller University in New York City to interview for the bioscience PhD program and began his graduate studies in Purnell Choppin’s lab in 1979. There, Roos found that the fusion-resistant mouse cell lines he had generated at Harvard had membranes with a distinct mix of lipids that directly correlated with their reduced ability to fuse with other cells, suggesting that the types of lipids present in the cell membrane control whether cells could merge with each other. He also found that cell fusion was not guided by changes in the fluidity of the cell membrane, which was previously hypothesized to be the way membrane fusion occurs. It was a really terrible idea to do something you’ve never done before when starting your own lab. You can’t train people in something you have never done before! In 1985, Roos joined Robert Schimke’s lab at Stanford University as a postdoc, to get the molecular biology training he was lacking. He studied the action of antifolate drugs—a class of chemotherapy agents that block the activity of folic acid—and developed an assay to test sensitivity and resistance to these compounds in cultured human cells. Roos applied for a Markey Trust fellowship, which provides funding for newly minted professors to start their own laboratories, but initially had no idea what research questions he wanted to address. He settled on parasitology for the “not very good reason that the research was relevant to parts of the world where I wanted to travel,” says Roos. After perusing the literature, Roos concluded that what was missing from malaria and other parasitology investigations were molecular genetic tools. He came across the work of Dartmouth’s Elmer Pfefferkorn, who had developed a plaque assay in which Toxoplasma would infect and lyse mammalian cells, in turn infecting their neighbors and generating plaques—pockets of lysed cells. The assay, Pfefferkorn had shown, demonstrated that generating Toxoplasma mutants was possible and could be used to do genetic crosses and identify biochemical pathways. “I proposed to develop an in vitro Toxoplasma culturing and transfection system to be able to add genetic markers in order to do molecular genetic experiments,” says Roos. Roos’s funding proposal failed to convince the reviewers, but his interest in parasitology nevertheless became invaluable to his career, establishing the research direction he wanted to pursue in his own laboratory. A bold move leads to biomarker success Researchers had previously tried to create genetic tools to manipulate Toxoplasma and Plasmodium by using the same type of anti-biotic-resistance biomarkers that were successful in yeast. But these attempts failed, and molecular biology experiments had stalled in the field of parasitology. So Roos took a different genetic marker tack, taking advantage of what he knew about antifolates as a tack to clone the organisms’ genes for dihydrofolate reductase, an enzyme required for the synthesis of the purines adenine and guanine and of some amino acids, and a target for certain chemotherapy drugs and antimicrobials. Roos began the genetic marker project while still in Schimke’s lab, but was only successful after he started his own laboratory at the University of Pennsylvania in 1989. He exposed parasites to antifolate drugs and selected cells that were resistant to the treatment and therefore must have had a mutation in their dihydrofolate reductase genes. In 1993, he cloned the gene for dihydrofolate reductase–thymidylate synthase (DHFR). With postdoc Robert Donald, Roos created a plasmid with a mutated version of the gene, which, when introduced into the parasite, results in antifolate resistance and can be used as a selectable marker. In 1998, using this genetic tool, Roos and postdoc Mary Reynolds uncovered how mutations in certain amino acids within the gene for DHFR alter interactions between the DHFR protein and antifolates, resulting in drug resistance. I find that science is a very aesthetically pleasing and artistically driven discipline in many respects. Looking back, Roos sees his younger self as overly bold. “If I had had any sense, I would have done a second postdoc and learned how to do this work with Pfefferkorn,” says Roos. “It was a really terrible idea to do something you’ve never done before when starting your own lab. You can’t train people in something you have never done before!” Roos also learned an important lesson from his Penn colleague Lewis Tilney. Roos initially wanted to have his postdoc advisor, Schimke, listed as an author on the dihydrofolate reductase paper. “The first draft listed Schimke because I started the work in his lab, but then Lou read the paper and said, ‘You’re the one that did all of the work. If you don’t call Schimke and tell him that he doesn’t need to be an author on the paper, then I will.’ So I called and of course Bob was very gracious and said that this was always my project. Lou had given me good advice, and I try to maintain that if I am not directly involved in the work, even if it’s done in my lab, then I am not an author on a paper.” Launching a bioinformatics career Even with his roots in laboratory biology, since 1998 Roos’s work has become subsumed by data management and integration. These days, with just a few postdocs and graduate students, his lab has “dwindled almost to vanishing,” he says. Since 2000, much of Roos’s time has been spent leading a team that is responsible for supporting EuPathDB, the Eukaryotic Pathogen Genomics Database, a catalog of parasites and other pathogens. He helps grow and manage the database as new omics data are generated by researchers around the world. A full-time staff of almost 50 people now maintains and updates the collection, funded mostly by the National Institute of Allergy and Infectious Diseases. The database began as a research question. After discovering the apicoplast in 1997, Roos’s lab wanted to understand the functions of the organelle in the context of other endosymbiotic organelles, and turned to evolutionary biology. Roos’s team identified some of the key apicoplast and nuclear genes necessary for the function of the organelle. In 1999, as the human genome was being assembled, the full genomic sequences of Plasmodium and Toxoplasma were still incomplete. Roos recognized that the parasite sequences that were emerging needed to be compiled, but that manually comparing sequences was not feasible. He also realized that the small computer programs his lab members had written to analyze their sequences of interest could be modified and used by others to ask their own scientific questions. That was the origin of the initial Plasmodium falciparum Genome Database (PlasmoDB) that Roos, along with then-postdoc Jessica Kissinger, launched in 2001. “Its success has come to dominate my life ever since,” he adds. The database continued to grow and now includes genomic and other omics data on 285 organisms, from fungi to pathogenic parasites. Roos’s initial interest in computer science has come full circle. “I want to create tools that allow other users to ask their own questions, rather than my being the ‘big computer scientist’ who does the analysis and then tells others an answer,” he says. “That philosophy is in line with what John Kemeny had in mind when he wanted anyone to have access to computers as a resource and to use them the way they want.” Isolated and biochemically characterized the lipid membranes of mutant mammalian cells altered in their membrane fusion properties Created assays to determine drug targets and resistance mechanisms in mammalian cells and protozoan parasites Developed molecular genetic and cell biological tools, including selectable markers for drug resistance, enabling the functional dissection of Toxoplasma and Plasmodium parasites and helping to launch the field of evolutionary cell biology With lab members Sabine Köhler and Maria Fichera, uncovered a novel organelle unique to parasites belonging to the phylum Apicomplexa, including Toxoplasma gondii and malaria-causing Plasmodium Developed the Eukaryotic Pathogen Genomics Database (EuPathDB.org), a data-mining resource facilitating the interrogation of multi-omic datasets relating to hundreds of microbial species, hosts, and diseases plasmodium toxoplasma gondii In Our Blood: A Profile of Stuart Orkin Microbe Miner: A Profile of Rob Knight Eye for Manipulation: A Profile of Elisabeth Bik Termination of USDA’s Toxoplasmosis Lab Concerns Parasitologists	cc/2019-30/en_head_0044.json.gz/line3322
__label__wiki	0.501386	0.501386	Allan May Allan May is the founder and chairman of Life Science Angels and chairman of the Kauffman Angel Resource Institute. More + Allan is a founder of Life Science Angels, the largest angel organization in the U.S. focused on early stage medical device and life science start-ups. Since 2005, LSA has invested $30M in 30 early stage companies, attracted in excess of $600M in contemporary or follow-on venture capital, and achieved four favorable exits. In 2010, Allan was elected Chairman of the Board of the Kauffman Foundation's Angel Capital Education Foundation. Allan has founded or invested in over 50 medtech and biotech startups, and lectures frequently on trends and developments affecting early stage biotech and medtech investing. Why Silicon Valley Is Running Scared From Health Care Who stole medtech's money? Blame the recession. And Twitter. Who Saved Silicon Valley? Angels, Of Course Like nature, capitalism abhors a vacuum, and Angels have been eager and able to capture the early stage space abandoned by venture capitalists.	cc/2019-30/en_head_0044.json.gz/line3323
__label__wiki	0.995914	0.995914	Australian prime minister announces May 18 election Polls open in tight Australia election Australian elections drive Manus Island refugees to despair and suicide Online histories bite Australian election candidates Polls tighten as Aussie leaders make final campaign pitches Australia's prime minister set to form majority government Pakistan arrests alleged mastermind of Mumbai terror attacks The election will pit Bill Shorten, a former labour union leader who has presented himself as the alternative prime minister for the past six years, and PM Scott Morrison, a leader who the Australian public is still getting to know. Prime Minister Scott Morrison speaks to the media during a press conference at Parliament House in Canberra, Australia. (March 20, 2019) (AAP Image/Andrew Taylor / Reuters) Australia's prime minister on Thursday called for a May election that will be fought on issues including climate change, asylum seekers and economic management. Prime Minister Scott Morrison's announcement came after he advised Governor-General Peter Cosgrove as representative of Australia's head of state, Queen Elizabeth II, to set the election date. "We live in the best country in the world," Morrison said announcing the widely expected May 18 date, arguing the future of the country depends on a strong economy. Morrison's conservative coalition is seeking a third three-year term. But Morrison is the third prime minister to lead a divided government in that time and only took the helm in late August. Opinion polls suggest his reign will become one of the shortest in the 118-year history of Australian prime ministers on election day. The polls suggest centre-left opposition leader Bill Shorten will become the eighth prime minister since the country plunged into an extraordinary period of political instability in 2007. The election pits Shorten, a former labour union leader who has presented himself as the alternative prime minister for the past six years, and Morrison, a leader who the Australian public is still getting to know. Morrison is seen as the architect of Australia's tough refugee policy that has all but stopped the people-smuggling traffic of boats from Southeast Asian ports since 2014. The policy has been condemned by human rights groups as an abrogation of Australia's responsibilities as a signatory to the United Nations Refugee Convention. Morrison's first job in Prime Minister Tony Abbott's newly elected coalition government in 2013 was as minister for immigration and border protection. He oversaw the secretive military-run Operation Sovereign Borders. Bill Shorten, the leader of the opposition Labor party, is the favourite to become Australian prime minister, opinion polls suggest. (February 13, 2019) (AP) "I Stopped These" Asylum seekers from the Middle East, Africa and Asia would typically disable or sink their boats when intercepted by patrol ships in waters north of Australia so that the Australian crews would have to rescue them rather than turn the boats away. Under the new regime, the asylum seekers were placed in motorised lifeboats that were towed back to Indonesia. The lifeboats had just enough fuel to reach the Indonesian coast. The Indonesian government complained the policy was an affront to Indonesian sovereignty. The government has also maintained a policy adopted in the final months of a Labor government in 2013 of sending boat arrivals to camps on the Pacific island nations of Papua New Guinea and Nauru. Those who attempt to reach Australia by boat are told they will never be allowed to settle there. Morrison remains proud of virtually stopping people-smuggler boat traffic. He has a trophy shaped like a people smuggler's boat in his office inscribed with "I Stopped These." Labor has promised to maintain the policy of banishing boat arrivals to the islands. But Labor says it would give priority to finding permanent homes for the asylum seekers who have languished in island camps for years. The conservative coalition argues that the boats would start coming again because a Labor government would soften the regime. The government introduced temporary protection visas for boat arrivals so that refugees face potential deportation every three years if the circumstances that they fled in their homelands improve. Labor would give refugees permanent visas so that they have the certainty to plan their lives.	cc/2019-30/en_head_0044.json.gz/line3325
__label__cc	0.546915	0.453085	Archive \| TOURISM Posted on 06 July 2019. By Grant Currin, Live Science Contributor \| July 5, 2019 A huge bloom of Sargassum seaweed is clogging up the Florida Keys. Credit: Brian Lapointe, Ph.D., Florida Atlantic University’s Harbor Branch Oceanographic Institute For eight years, thick mats of seaweed have smothered coral reefs, trapped sea turtles and brought economic instability to coastal communities as reddish-brown gobs of foul-smelling sargassum wash onto beaches along the Caribbean Sea, Gulf of Mexico and tropical Atlantic. These phenomena are symptoms of a massive seaweed bloom scientists are calling the Great Atlantic Sargassum Belt. Researchers describe the belt and explore its causes in a study published July 4 in the journal Science. Stretching up to 5,500 miles (8,850 kilometers) from the Gulf of Mexico to just off the coast of western Africa, the Great Atlantic Sargassum Belt appears to be the product of natural and human-caused factors. video playing What’s Behind the Massive Midwestern…23/03/19 Lost City in South Africa Discovered with Laser…15/03/19 First Video of Antarctica’s Massive…13/02/18 Cannibal Chimps and Life-Saving Watches20/10/17 Watch These Dinosaur Puppets Come to Life24/08/17 “We analyzed almost 20 years of satellite records,” Mengqiu Wang, a postdoctoral researcher at the University of South Florida and co-author on the study, told Live Science. [Earth from Above: 101 Stunning Images from Orbit] The researchers analyzed a dataset that predates the belt’s first appearance in 2011, allowing them to investigate the long-term environmental changes that set the stage for the year-to-year variations in the growth of the bloom. They identified a tipping point around 2009 when discharge from the Amazon River brought unusually high levels of nutrients into the Atlantic Ocean. Upwelling of nutrient-rich water off the west coast of Africa in the winter of 2010 further enriched surface waters with deep-sea nutrients; that upwelling also lowered temperatures of that surface water, allowing sargassum to thrive in the summer of 2011. A similar combination of factors led to especially large blooms in 2014, 2015 and 2017. The largest recorded bloom occurred in 2018, when the Great Atlantic Sargassum Belt grew to a mass of more than 20 million metric tons. The high levels of nutrients from the Amazon River come from deforestation and fertilizer use in the Amazon basin. Under normal circumstances, sargassum provides critical habitat for marine life. The seaweed oases attract fish, birds and sea turtles as well. Dolphins and sea turtles also benefit from the tiny patches of life floating in the open ocean, but thick mats of sargassum pose big problems for some wildlife and coastal communities. Mengqiu Wang was performing field work in the Gulf of Mexico last year when she saw dolphins seeming to enjoy their foray through the Sargassum. Credit: University of South Florida “As sargassum decays it consumes the oxygen, creating low oxygen conditions, which is not a good condition for marine life in a coastal ecosystem,” Wang said. Coral reefs and seagrass ecosystems can suffer when high levels of sargassum change water chemistry and block organisms from moving freely. “Sea turtles sometimes can’t swim through the dense mats to return to open water after laying their eggs,” she said. The Great Atlantic Sargassum Belt is also having an effect on coastal tourism. Barbados declared a state of emergency in 2018, according to a government statement, as sargassum piled onto the beaches the island nation relies upon to draw tourists. “The negative impacts occur when sargassum starts to pile up on the beaches,” Wang said. In addition to disrupting coastal ecosystems, decaying sargassum releases hydrogen sulfide, a potentially harmful gas that smells like rotten eggs. The 10 Weirdest Sea Monsters 13 Bizarre Things That Washed Up on Beaches 25 Strangest Sights on Google Earth Posted on 21 June 2019. Adapted : Thursday, June 20, 2019, Nearly all islands across the Lesser Antilles are experiencing air quality levels that are unhealthy for sensitive groups, with the most reduced air quality occurring across Barbados and Martinique as of 11:00 AM. Dense Saharan Dust continues to traverse the Atlantic and Caribbean as all islands across the Greater Antilles, stretching as far as Florida into the United States, are experiencing moderate air quality. Across Trinidad and Tobago, air quality is beginning to deteriorate rapidly, but generally still at good to moderate levels. Persons with respiratory ailments, heart disease, the elderly and children need to take the necessary precautions! Presently, minimal to mild concentrations of Saharan Dust are present across Trinidad and Tobago, with air quality at good levels across Western and Central Trinidad. Across Eastern Trinidad and Tobago however, a combination of model data and ground stations are indicating air quality is beginning to be quickly degraded, presently at moderate levels. Air quality index across Trinidad and Tobago as of 11:00 AM Thursday 20th June 2019 as dense Saharan Dust forecast to continue moving across the region. According to the EMA, the national standard for Particulate Matter (PM) of diameter ≤2.5 µm (PM2.5) is 65 µg/m3 and PM of diameter ≤10 µm (PM10) is 75 µg/m3. This has not been exceeded since the March 2019 Saharan Dust Outbreak. Based on present model guidance, this event is expected to become close or just over the PM2.5 threshold at 62-66 µg/m3 at its peak early Friday morning across Trinidad and Tobago. In addition, with breezy conditions, and gusts to 60 KM/H, a significant reduction in visibility is forecast out at sea. Marine interests are advised to exercise extreme caution as seas still remain moderate, with waves between 2.0 to 2.5 meters in open waters. All Lesser Antilles Islands are experiencing air quality levels at unhealthy for sensitive groups, with the exception of Trinidad and Tobago. Countries along the Northern coast of Southern America are experiencing good air quality, while all Greater Antilles islands, stretching as far west as the United States, are experiencing moderate air quality. Air Quality across the Eastern Caribbean and the Greater Antilles At moderate air quality levels, unusually sensitive groups should consider reducing prolonged or heavy exertion. The concentration of the dust that follows the wave depends on the strength of the wave as it moves off the West African Coast. This is because of stronger thunderstorms across Central Africa. As strong winds move downward and outward from these thunderstorms, the wind kicks up dust as it moves across parts of the Saharan Desert and transports it into the upper atmosphere. This “plume” of dust follows the axis of the wave as it progresses westward into the Atlantic. 5-Day Air Quality Index, Saharan Dust Forecast For Trinidad and Tobago. A significant surge of Saharan Dust is forecast to move across Trinidad and Tobago over the next 24-48 hours, reducing air quality to unhealthy for sensitive groups for the 3rd time in 2019. Air quality is forecast to return to good levels by late Saturday into Sunday as Tropical Wave 10 moves across the area. Dust models continue to show, following the passage of tropical waves, moderate concentrations of Saharan Dust moving across Trinidad and Tobago over the next several weeks. Based on the latest model guidance, following this significant surge over the next 24-36 hours, another moderate surge is forecast by June 25 and another by June 30. 00Z June 20th 2019 NASA GEOS-5 Dust Model showing several surges of Saharan Dust moving across Trinidad, Tobago and the Eastern Caribbean over the next 10 days. Credit: Weatherbell Sensitive groups such as persons with respiratory ailments, children, the elderly and cardiopulmonary disease should take the necessary precautions on days where dust concentrations degrade air quality to moderate to unhealthy for sensitive groups. Saharan Dust Precautions Posted in Business/Economy/Banking, CARICOM, Climate/Weather, Education, Environment, Featured, International, Local, News, Regional, Science/Technology, TOURISM0 Comments PORT OF SPAIN, Trinidad, Jun. 4, CMC – The Caribbean Development Bank (CDB) has approved a recent grant for the Caribbean Community (CARICOM), that will make regional trade easier . On Monday, the Bank’s Board of Directors signed off on CDB’s support of US$43,665 in grant funding to finance completion of the CARICOM Interactive Marketplace and Suspension Procedure Portal (CIMSuPro). The CDB says the portal’s development makes it easier for CARICOM states to administer the common external tariff (CET), the system underpinning regional trade, which all CARICOM states are required to maintain. The CET is a uniform set of tariffs imposed by CARICOM members on goods from third countries. The regional lending agency noted that suspension of the CET can be granted to allow importation of goods in short supply within the Region. However, information on the actual supply of goods in CARICOM is limited and officials grapple with a high volume of CET suspension requests. CIMSuPro seeks to encourage more intra-regional trade by allowing buyers to find regionally produced goods as their first option. The portal allows buyers to find appropriate regional products by description or tariff code. It also provides an on-line mechanism to create a faster process to handle CET suspension requests. CDB’s funding will support training and technical support for trade officials and traders. Director of Projects at CDB, Daniel Best expressed optimism that the portal would contribute to a more enabling environment for Regional manufacturers and producers, saying: “CIMSuPro is designed to take the CSME process a step further by allowing our producers and our retailers to find each other more easily. CSME is intended to give our producers access to the larger regional market and to leverage economies of scale. A fully operational CIMSuPro will bring greater certainty to intra-regional trade.” The project is aligned with CDB’s strategic objective of supporting inclusive growth and sustainable development as well as its corporate priority of promoting private sector development, competitiveness and innovation. EU launches fund to assist Caribbean countries BRIDGETOWN, Barbados, CMC – The European Union has launched a Euro 28 million (One Euro=US$1.29 cents) Regional Climate Resilience Building Facility that will provide financial resources for technical assistance, disaster insurance and resilient investment facilitation. The facility is the largest grant-funded resilience building project in the Caribbean to date and will be implemented by the World Bank and the Caribbean Catastrophe Risk Insurance Facility (CCRIF). EU Ambassador, Daniela Tramacere “What we want from this programme is to address real needs. For this, governments and partner entities will have to define clear priorities, without which a targeted implementation is not possible,” said EU Ambassador, Daniela Tramacere, at the weeklong Understanding Risk (UR) Caribbean Conference that is organized by the World Bank in partnership with the Barbados government, the Caribbean Disaster Emergency Management Agency (CDEMA) and the EU. The EU diplomat said the action should have as its ultimate objective, the genuine interest of Caribbean citizens translated in terms of resilience building at community and individual levels. The technical assistance aims to strengthen the capacity of public institutions and civil society organisations which are capable of protecting citizens from disasters. The support to the Caribbean Catastrophe Risk Insurance Facility will help countries cope and recover better from the effects of extreme weather events. “The support to resilient investment will stimulate the private sector to better adapt businesses and jobs to the priority needs of countries and citizens,” she added. The Regional Resilience Building Facility is one of the many resilience programmes being financed by the EU in the Caribbean. Additional support for countries to build societal resilience by encouraging the transition to green economies and progress towards a sustainable economic path is being provided by various other EU programmes. The EU said it is also partnering with regional governments and institutions on climate adaptation and ecosystem resilience and on hydrological meteorological data gathering. Earlier this week, Canada also announced the launch a CAD$20 million (One Canada dollar=US$0.74 cents) Canada-Caribbean Resilience Facility initiative to help regional countries better prepare for and respond to natural disasters. “This initiative is being undertaken with Canada’s Caribbean support as a direct response to the lessons learned following the devastating hurricanes in the Caribbean in 2017 that have impacted our neighbouring countries so severely,” says Marie Legault, High Commissioner of Canada to Barbados and the OECS. Posted in Business/Economy/Banking, Climate/Weather, Earthquake, Environment, Hurricane, International, Local, News, Regional, TOURISM0 Comments Ferry – Jaden Sun Information coming out of the Government Information Unit informs: “This weekend with the upcoming holidays will see significant changes that will affect both stakeholder and customers significantly.” The result of that is that the current month will see a number of changes to the Ferry schedule, as follows: Friday, June 7th 2019 – No Day Tour (Regular Morning and evening Svc in place) Saturday, June 8th 2019 – Day Tour Service in place Sunday, June 9th 2019 – No Ferry Service Monday, June 10th 2019 – Day Tour Service In place Tuesday, June 11th, 2019 – No Day Tour (Regular morning and evening svc in place) It seems early, but the release noted: “the Access Division’s Buju Trip to St. Kitts scheduled for June 29th, 2019 is cancelled due to low uptake.” Special note is invited to the following: From July 6, 2019 ALL Sunday services will depart Montserrat at 10:00 a.m. arriving Antigua at 11:30 a.m. The Departure times out of Antigua remains the same. The Division is reminding that check-in closes 30 minutes before departure. Then, “All agents and customs and immigration personnel, please advise your staff on these changes.” by Bennette Roach Much of the external renovation and reconstruction is well underway Joseph O’Garro is the Manager of the Montserrat Port Authority, recently referred to as the Chief Executive Officer (CEO) at the recent Port Development launch last week. He invited the media to what he said was a simple briefing exercise to alert the public, “so they can know and appreciate what was taking place in terms impact to them when they come to clear their cargo…” That was the morning of Friday, May 24, 2019 at the Little Bay port building that houses offices and cargo storage. O’Garro briefly outlined that the works that began couple weeks ago, and was ongoing when the launch took place at the ferry terminal about 100 yards away, on Friday 17th. He apologised for other members of the management team who he said he would love to be present at the informal briefing, but they were about getting ready to effect the relocation of the offices, as the works were well into full gear. He introduced those present in Stephie Buffonge from the Comms and Works and Adrian Galloway of Galloway Group who had been awarded the contract to carry out the works, which had an estimated budget total of EC$890,000, which is partner-financed. He referred to the project as a follow-up of the marine side of the new port development launch in terms of the “landside works that are being undertaken separate and apart to the project, but in support of the project itself.” The works he said, will be about the offices, administration, Customs and customer area renovations, currently engaged in a material fashion. He explains that the layout as it stands is not very customer friendly, as he later pointed out on the external, the construction of ‘disability access’ to make the premises and the offices accessible by everyone. “Some of the works undertaken will address the customer friendliness of the facility ensuring we are much more customer oriented. In addition, we are providing additional space for Customs as the accommodation is presently very cramped…” He added that for the MPA itself they are expanding their own offices to “facilitated some of our expanded national responsibilities,” with regards to their maritime responsibilities that did not receive as much attention in the past as it should have. He explained: “We will be providing for some additional office space to facilitate some of our expanded national responsibilities, our marine time responsibilities that would not have received as much attention as it should have in the recent past…just examining vessels when they come into our Port, to know that they are compliant with international standards.” He added, “We intend to embrace a lot more of that responsibility going forward and as such we a going to provide the office space for our officers to work comfortably while they engage in those activities.” Upgrading to facilitate the disabled, and wheel chair access One of the initial steps is to ensure that the Port Authority and Customs are in a better position to handle the increase business that we expect and to upgrade the facility…so that we’re more customer focused. The partner-financed sum of $890,000 is shared with the MPA providing $500,000, with GoM the balance of $390,000. O’Garro explains the external renovations and relocations Following a brief explanation of the drawings and the work progression by Galloway and Buffonge relating to the project, the manager now with support of some senior staff provided a tour of the quarters that will housed in temporary accommodation in the parking area where the staff will effectively meet the needs of the public. And of course, to facilitate the construction office operations for both Customs and the Port, “are being relocated to the parking lot into temporary accommodations, as of Monday.” The project is expected to be completed within six months. see related: https://www.themontserratreporter.com/new-port-development-launched Concept design – Full to be available by August The Government of Montserrat through the Ministry of Communication and Works on Friday, May 17, 2019, conducted the Montserrat Port Development Project Launch which has been seriously undertaken when Premier Romeo announced in February last year, that the funds had been sourced for the project. The event was hosted at the Montserrat Port Authority – Ferry Terminal Building, with an overflow of persons who were outside of the small available space, but with the apparent intention to afford guests the opportunity to tour the site and to ask pertinent questions, especially that there is not yet a design for the actual port. Port Authority manager Joseph O’Garro chaired the proceedings which began with the singing of the Territorial song and a prayer led by Fr. Carlisle Vyphius of the Anglican church. Following, were welcome and opening remarks by the port manager, referred to as the Chief Executive Officer – Montserrat Port Authority on the program; H.E. Governor Pearce, CDB Representative Andrew Dupigny, Head of Infrastructure Partnerships, Hon. Paul Lewis, Minister of MCWEL, a feature address by Premier Donaldson Romeo and finally a vote of thanks by MCWEL Permanent Secretary, Mrs. Beverley Mendes. Seated in the front row l-r, Governor, Premier, Minister, Dupigny and PS with CDB officials in the back row Mr. O’Garro briefly in his opening and welcome outlined what most or all of the remarks noted, that the project will provide safe, secure and modern port facility for Montserrat, that will provide critical access and reduce down-time especially in times of poor weather. He, again like others, in addressing the down time noted that about 12% of the vessels calling at Little Bay had not come into, or leave or port. CEO O’Garro and Governor Pearce The Governor said about the project. “It works with the grain of our small island community and it sort of aligns with the niche nature of our economy,” preceding that with the observation. “Size is not everything, quality and balance are key – it matches the scale of little Montserrat – we aren’t going to get and we don’t want almost 4000 berth cruise ships, hopefully smaller ones – we can host graciously… CDB’s Andrew Dupigny, who has been with the project from early 2017, in his remarks, noted that, “…On completion it is expected that the new facility will provide direct and positive impact on the economy with the potential that would increase employment, improved productivity and overall improvements in the business environment. Andrew Dupigny Sounding like coming straight out of a business case, he continued to say: “Over the long term the provision of a reliable access and connectivity to the island, the movement of people goods and services would increase its creativity potential which would ultimately positively impact growth – improve the efficiency effectiveness and resilience of the port facility to provide safety and accessibility.” – When we say that this project goes way, 12 years, further than the Premier would later recall, Dupigny noted “This actually dovetails very well with the government of Montserrat’s ongoing activities to restore access and connectivity to the island,” which he said, “…was articulated in the Hon Premiers presentation of the budget address in 2017 when he declared ‘access is perhaps our single biggest challenge to growth.’” He connected this to: “CDB’s strategic plan for the period 2015 to 19 similarly recognises, the positive relationship between infrastructure economic growth and poverty reduction.” He offered, “Good transportation is one of the main elements that supports national development. A Key success of any project especially a project such as this which will impact every community across Montserrat is the participation of stakeholders.” “We are therefore extremely pleased to see the enthusiasm evidenced by your numbers here this morning as well as a high level of participation in the workshop that took place over the past few days.” This was a workshop that this long-standing stakeholder in all Montserrat progress media house was excluded and knew nothing about. Such could very well be to the detriment to any project, except for dishonest follow-ups which in the end will as we say be detrimental to Montserrat. Minister Lewis was firm in his presentation as he set out the history of loss and difficulties with a port that far than less served the required needs of Montserrat, but finally, “a solution.” He spoke to how, “with unreliable sea access for the last 23 years Montserrat lost opportunities for economic growth, our country’s people suffered other losses, including vessels running aground and the destruction of cargo vessels; loss of fishing vessels and yachts unable to come into port; cost of goods have increased after additional charges were placed on shipping given the uncertainty of docking on arrival in Montserrat and having to wait, perhaps even leave before returning a second time to off load,” referring to unsuccessful attempts as they try to dock in rough waters, having to return to Antigua – the road to a solution has not been without challenges. He spoke of the benefits to be gained as the project progresses, as well as the revealing that, “The project will also provide employment for 72-100 workers over 18 months to two years. With all other requirements in place and September this year, for a design and build contractor will take place, thereafter, the successful company will be mobilizing to start work by the end of the year Funding for this project, after a £23 million offer by the UK was turned down (technically) in early 2014, came with a £14.4 million grant to GoM from the UK government via the United Kingdom Caribbean Infrastructure Partnership Fund (UKCIF), augmented by another £7 million budgetary support from the European Union. With the (CDB) making an initial allocation for the project, advised to GoM in July 2016, an application for the grant made in March 2017, the agreement between the Caribbean Development Bank (CDB) and the Government of Montserrat for £14,400,000 was signed by Premier Romeo on Wednesday, April 11, 2018. Premier Romeo and Minister Lewis The Premier was set to deliver the feature address for the event. He, following what took his Government nearly three years to get to this point, recently accessing the needed additional funds, he was relieved probably more than excited. “Today, marks one of the first, breakthrough step towards the fulfillment of a twenty four-year old hope for Montserrat; a protected sea port here in the safe zone. Yes, the first safe harbour in Montserrat’s history,” he began. He continued by recalling as many of the arguments that had no doubt, like Dupigny recalled, made in the business case that had to be presented for the port. He quoted DFID: “The principal barrier to economic growth and development on the island is poor physical access.. . . Without the development of Little Bay and Carr’s Bay, improved access, and reduced costs of doing business, Montserrat will remain uncompetitive in attracting [Foreign Direct Investment].” So he told an appreciable number of many of whom were invited for the event. “The port development project is therefore one of the strategic keys for unlocking growth and building Montserrat’s future.” Concurring that this key we will open up the door for local and foreign investment and for self-sustaining, private sector led growth, he added: “It will create jobs during the construction phase, and it will provide more reliable docking for Cruise ships and for cargo vessels.” Like other speakers he pointed out that “due to rough seas…out of a total of 478 calls, vessels were unable to berth 58 times…one vessel out of every eight had to turn back. “Yes, that is not sustainable. We had to fix the problem,” he said That’s why a safe harbour “is of vital importance in providing connectivity to the island of Montserrat and for supporting economic activity.” He reminded of earlier attempts at building a port, that the Government of the day had envisioned a sea port development in Carrs Bay, and it had actually knocked down part of Gun Hill to facilitate the project. With no design yet in place for the current project, he noted that in the previous case, a design was made and developed, being presented to the public at 60% and 90% points. “But, alas, it was very costly and suitable private sector partners were hard to secure,” but giving no details of the contrasts. He recalled also a statement made by former Chief Minister John Osborne, deceased, in the aftermath of Hurricane Hugo on July 30, 1990: “With assistance in developing its infrastructure, including a proper airport and a safe harbour, Montserrat could develop a viable economy and opt for independence.” Before closing his address, the Premier gave an insight as to how the project will move from this launch. “First, through presentations and workshops that have been going on for a few days, we look at preliminary designs, then adjust towards a preferred option. The preferred option will then be fully developed as a technical design, starting in August. Then, once that design is completed and accepted, construction will begin. He revealed that “Construction will take considerable time, over a year,” with a caution. “However, we must always recognise that we are dealing with the sea, which has its own power, its own ways and its own voice; which can force changes to our proposed schedules.” He concludes after thanking several key authorities, Minister Lewis, UK govt and other key personel, and then: “Let us see, how we can work together as a people as we put in place one of the foundation stones for building our future.” Discussing the possible design The P:S gave a fairly descriptive and comprehensive vote of thanks, praising the Ministry and staff for the work done so far on the project and hosting the morning’s event which ended with people looking at and discussing the site from the concept drawing. Related: https://www.themontserratreporter.com/planning-to-begin-for-a-breakwater-facility-at-little-bay/ Grant funding of GBP14.4 m to develop port at Little Bay, Montserrat https://youtu.be/jhkzwryf-2w “https://drive.google.com/drive/folders/1-cZXxLq1fMwTeH0q5kA4vBcaQdyCsAbz?usp=sharing https://www.youtube.com/watch?v=jhkzwryf-2w&feature=youtu.be Participants at the strategy workshop Tourism Intelligence International Inc. completed a Tourism Strategy for Montserrat. Following a comprehensive tour, by the consultants who completed many one on one sessions, facilitated a stakeholders’ workshop in February, they submitted a draft to which comments were sought to be used to create the best path forward for Montserrat Tourism. A strategy was written and approved in early April after a deadline for submission of comments by March 11, 2019. Here is a brief report of how the workshop in February progressed. Dr. Auliana Poon In the course of the February 14, 2019 Montserrat Tourism Strategy Workshop, Dr. Auliana Poon raised the questions, Montserrat’s vision 2050 and Montserrat’s uniqueness. Participants were invited to write on small strips of paper which were then posted on wall charts. In trying to summarise Montserrat’s uniqueness, participants suggested: Hassle free living Strangers paradise The Montserrat Oriole and Galliwasp The active/living beautiful volcano The volcano experience Buried city Clean, reliable water Nature lovers’ paradise Safety/negligible or low crime rate Lowest crime rate regionally Dark skies at night for stargasing Our collective experience in our specific environment (thus, history, culture, volcano impact) It is the way the Caribbean used to be Close-knit Very easygoing lives Getting here is an achievement Culture and festival diverse No traffic (issues) Natural spring water Exclusive black sand The gist of these themes suggests that our key tourism and development assets are tied to our natural and cultural heritage, with particular reference to tranquility, peacefulness, friendliness greenness and the spiciness of a drive-in active volcano experience. At the same time, it was clear that it was a struggle for some participants to see the volcano as a value driver. Perhaps, also, we need to ponder to what extent we suffer from post-traumatic stress disorders, even in the midst of celebrating resilience. In this context, Dr Poon’s other question on where we hope to be in just thirty-one years’ time, opens up another window on ourselves. In other words, if we now are how the Caribbean used to be, where do we want to go in the next generation? Participants suggested: The way the Caribbean used to be Green, tranquil, inclusive and safe Clean, green connected and beautiful Clean, green and self-sustaining Water, black sand, friendly people Sustainable 100% Crime free Viable Booming Connected, green, thriving Dynamic tourism industry Competitively involved Fulfill the National Vision (buoyant, inclusive, prosperous, God-fearing) Wholesome, sustainable Crime-free, God-fearing Sustainably developed Economically efficient Green, evolving and receptive Highly valued Here, we may see that there is a desire to keep the best of what we have and to gain self-sustaining prosperity in a green, wholesome, beautiful, God-fearing way. Now see the completed strategy here: http://www.gov.ms/wp-content/uploads/2019/04/2019-03-29-Montserrat-Tourism-Strategy-2019-2022.pdf? Posted on 05 April 2019. Nerissa Golden LITTLE BAY, Montserrat – Author and Business Coach Nerissa Golden has been appointed to act as Director of the Montserrat Arts Council (MAC) until a substantive head is found. The acting director along with member of the MAC Board Reinford “Kulcha Don” Gibbons attended the Regional Cultural Committee meeting in Trinidad last week to be updated on the plans for hosting CARIFESTA and other issues related to the development of cultural industries. Golden, who sat on the board of directors for two years, resigned in order to take up the current position. She will oversee internal restructuring of operations, as well as prepare for Montserrat’s representation at the CARIFESTA XIV in Trinidad & Tobago this August. Golden is a former Director of Information & Communications for the Government of Montserrat. She is the author of eight books and has managed the Discover Montserrat media platforms for the past four years. One of her priorities, will be to support the establishment of new governance structures as mandated by the board and the development of a revised cultural policy for the island which aligns with local and regional focus to build the creative sector. Former director Chadd Cumberbatch ended his secondment to the council from government at the end of March. Chairman of the MAC Board Albrun Semper said they were grateful for Mr. Cumberbatch’s contribution to building culture and wished him success in his future endeavours. The council recently closed its call for applications for two senior roles, Director of the MAC and the Head of Planning & Production on Friday, March 29. Montserrat hosts the Red Ensign Group Conference The event was little publicised (in Montserrat), but it was a big conference with an international flavour as the Red Ensign Group Conference was held this year for the first time in Montserrat. The conference which is an annual gathering of the British ship registers opened at the Montserrat Cultural Center and ran from April 2 – 4, 2019, with representatives from UK Government who meet in a different territory each year on a rolling basis. Members representing the British ship registers and coastal state coordinators from across the Red Ensign Group were in attendance. Joseph O’Garro The opening session was brief and to the point, opening in the usual fashion with National Anthem, (it being a UK organisation/conference; a Welcome by Mr. Joseph O’Garro, Manager, Montserrat Port Authority, main organiser on the ground, and who chaired the session; and prayer Opening Remarks Honourable Donaldson Romeo, Premier, Special Remarks His Excellency the Governor, Mr. Andrew Pearce; Special Remarks Miss Katy Ware, Chair of The REG Conference; all followed by Closing Remarks Honourable Paul Lewis, Minister for Communications, Works & Labour (including Maritime Affairs); ending with a Vote of Thanks Mr. Ashley Lindsey, Access Coordinator, out of the Office of the Premier; and the singing of the Territorial Song, and the dismissal. The conference then got on the way to conclude on April 4. Katy Ware, director of maritime safety and standards at the Maritime & Coastguard Agency chaired the conference (at least at the opening). She said: ‘The Red Ensign Group conference matters because it brings us all together to work through those matters of regulation related to flag, port and coastal state responsibility that give us our status as a leading maritime player across the world. Everyone has an equal voice and there is a relationship between us that makes things happen.’ Katy Ware She added in her opening remarks a message to delegates from @Nus_Ghani: ‘You share common goals and common objectives … and you’ve done outstanding work in maintaining the reputation of the Red Ensign Group.’ The bell opens and ends the sessions – https://twitter.com/i/status/1113117714070102017 Information from the conference said “it is a great opportunity for detailed face-to-face discussion of a wide variety of matters of shared interest and to share best practice and discuss ways to optimise performance of the British register in the international arena, both in terms of commercial success and in setting exemplary standards in meeting our international maritime obligations. It is also an opportunity to look at the challenges of meeting Coastal State obligations and share ideas of how to improve those. “But more than that is a way to get to know each other which helps the registers work together to drive the success of the total British registered tonnage, which at over 50 million gross registered tons is one of the world’s larger registers with a real part to play at the International Maritime Organization and in influencing international maritime matters.” Governor Pierce Governor Pierce tried to be brief, in his remarks shared with the delegates his own love and impressions of Montserrat having just completed just over a year on the job, inviting them to enjoy and appreciate the island. In the end he wished them: “Have a good fulfilling conference.” Premier Donaldson Romeo Premier Romeo in his remarks to the conference began quoting TV personality and entrepreneur Jimmy Dean who said that “I can’t change the direction of the wind, but I can adjust my sails to always reach my destination.” “This’” he said as he was quick to speak of Montserrat’s upcoming newest project, “is the secret of Montserrat’s resilience in the face of the volcano crisis, and as we begin to create the first ever protected harbour in Montserrat, we are confident that the maritime sector will make a huge contribution to our redevelopment. That is why we are committed to the maritime industry.” The Premier said that our tourism sector is largely dependant on sea access and on our marine infrastructure, and, making the announcement, “That is why, as Minister of Tourism, I am happy to announce Cabinet’s approval last Thursday of the Tourism Strategy 2019-2022.” “So, in this spirit of optimism,” he said, “I welcome the Red Ensign Group (REG) Conference to Montserrat; with over 70 delegates, including representation from the United Kingdom, nine British Overseas Territories and three Crown Dependencies…” noting that the combined British Red Ensign fleet is the 9th largest in the world and that the Conference is a means to help oversee and uphold maritime safety standards across the thirteen British Shipping Registers. In his brief remarks, the Premier noted also, “This conference is also being held at a strategic time, as the global maritime industry is facing major changes in safety and security.” Minister Paul Lewis The Honourable Paul Lewis, Minister for Communications, Works & Labour (including Maritime Affairs) for which he is the Minister responsible gave Closing Remarks which he began by welcoming the delegates, from as he said, as far as St. Helena with their travel challenges, “notwithstanding their new airport.” The Minister referred to several good news items and projects which deserve mention and will be revealed and reported on later. He brought his remarks to a close by recognising the international quality of the flag states while also acknowledging the tremendous efforts of the Montserrat Maritime administration and the Montserrat Port Authority, as well as the various multisector resources drawn from Government departments including the office of the Premier – all of whom were engaged in preparing for the successful hosting and delivery of the REG conference 2019. Finally, a vote of thanks was delivered by Ashley Lindsey, Access Coordinator and the singing of the Territorial song very ably and beautifully rendered by Mrs. Mildred Chalmers. Vote of Thanks delivered by Mr. Ashley Lindsey A photo from the Conference 2019 Day 2, showing all the delegates from across the 13 members! In the following days, a few reports were available as to the progress of the conference. Day two of #REG2019 was reported as, “another day of collaborative working and productive discussions all around regulation, coastal state preparedness and registration. Everyone has something to give.” Anguilla delegates in a mention, said the coastal state session at #REG2019 Conference will help them in their ongoing work to meet their maritime obligations. It’s part of #CSSF work funded by the UK Government. The information came out that Sarah Morgan, head of Registry of Shipping & Seamen who was selected to chair the Red Ensign Group #REG2019 Registrars session in Montserrat. Listen to a comment from her. https://twitter.com/i/status/1113897794161512451 Guernsey’s Harbourmaster Captain David Barker and other delegates from the @RedEnsignGroup have been touring the British Overseas Territory of Montserrat as part of the #REG2019 conference taking place. It was affected by a volcano eruption in the 1990’s. @MCA_media@gsyharbours Conference began with prayer – head table stands: Joseph O’Garro, Katy Ware, Governor Pierce, Premier Romeo and Minister Lewis Anthony Albanese warns PM: don't play politics with drought funding https://t.co/EDYRPsybnE But will Dems still vote against war if a Democrat is in the White House? https://t.co/liwKWRqnYq BBC News (World)@BBCWorld· Christian family fined after arguing taxes 'against God's will' https://t.co/tjkEyYWvAA Newly independent Rep. Justin Amash welcomes Mark Sanford's potential primary challenge to Trump https://t.co/kIeWHmpFrK A compound found in the skin of grapes could be part of the dietary strategy that keeps astronauts strong on Mars https://t.co/MO6rz70Iel	cc/2019-30/en_head_0044.json.gz/line3326
__label__wiki	0.832688	0.832688	Seychelles president's underwater speech: Protect our oceans By The News · 18 of April 2019 08:30:11 AP Photo,, No available, Seychelles President Danny Faure emerges from the ocean inside a submersible, off the coast of Seychelles on Sunday April 14, 2019. In a striking speech delivered from deep below the ocean's surface, the Seychelles president on Sunday made a global plea for stronger protection of the "beating blue heart of our planet." President Danny Faure's call for action, the first-ever live speech from an underwater submersible, came from one of the many island nations threatened by global warming.(AP Photo/Steve Barker) DESROCHES ISLAND, Seychelles (AP) — In a striking speech delivered from deep below the ocean’s surface, the Seychelles president on Sunday made a global plea for stronger protection of the “beating blue heart of our planet.” He spoke during a visit to an ambitious British-led science expedition exploring the Indian Ocean depths. Oceans cover over two-thirds of the world’s surface but remain, for the most part, uncharted. We have better maps of Mars than we do of the ocean floor, Faure said. Wearing a Seychelles T-shirt and shorts, the president told The Associated Press after his speech that the experience was “so, so cool. What biodiversity.” It made him more determined than ever to speak out for marine protection, he said. “We just need to do what needs to be done. The scientists have spoken.” Small island nations are among the most vulnerable to sea level rise caused by climate change, and some have found creative ways to express their concerns. Faure’s speech came a decade after members of the Maldives’ Cabinet donned scuba gear and used hand signals at an underwater meeting highlighting global warming’s threat to the lowest-lying nation on earth. Land erosion, dying coral reefs and the increased frequency of extreme weather events threaten such countries’ existence. By the end of the mission, researchers expect to have conducted over 300 deployments, collected around 1,400 samples and 16 terabytes of data and surveyed about 30 square kilometers (11.5 sq. miles) of seabed using high-resolution multi-beam sonar equipment. While scientists with the Nekton mission are nearing the end of their expedition, much of their work is just beginning. In the next few months, researchers at Oxford will analyze the samples and video surveys and put them together with environmental data. Associated Press writer Frank Jordans in Berlin contributed. Follow the mission at https://apnews.com/SeychellesOceanMission Follow Africa news at https://twitter.com/AP_Africa	cc/2019-30/en_head_0044.json.gz/line3328
__label__wiki	0.942176	0.942176	Ascend P2: China’s Huawei claims world’s fastest smartphone by AFP February 25, 2013 July 4, 2014 Barcelona: China’s Huawei, the number three smartphone maker behind giants Samsung and Apple, unveiled Sunday a new mobile, the Ascend P2, which it claims is the fastest in the world. Sharp-cornered and thinner than a pencil at 8.4 mm, the company said it can achieve speeds of 150 Mbps, fast enough to download a two-hour high-definition movie in less than five minutes. The mobile, which has a 4.7-inch, high definition screen, has a powerful 1.5 GHz quad-core processor and is able to use the fourth-generation high speed mobile networks being rolled out worldwide. Unveiling the device on the eve of the opening Monday of the four-day Mobile World Congress in Barcelona, Spain, the company said it was “the world’s fastest smartphone,” smashing all previous records. A man holds Huawei’s new smartphone, Ascend P2, after a press conference in Barcelona on February 24, 2013 © AFP Huawei said its phone surpassed top speeds of 100 Mbps for the fourth-generation network ready versions of Apple’s flagship iPhone 5 and Samsung’s Galaxy SIII. The Ascend P2 will launch in France through Orange in June and is also expected to be available worldwide during the second quarter of 2013, it said. “Ascend P2 downloads HD movies in minutes, and loads online videos, web pages, songs or e-Books in seconds,” Huawei said in a company statement issued at the launch. The phone, which includes a 13 megapixel camera, is the latest shot in Huawei’s battle against the fast-growing market’s titans Samsung and Apple. Samsung and Apple accounted for more than half of all smartphone sales in the final quarter of 2012 — 29.0 percent for Samsung and 22.1 percent for Apple — according to research firm Strategy Analytics. Behind Samsung and Apple, however, Chinese firms held the third, fourth and fifth spots — with 5.3 percent for Huawei, 4.7 percent for ZTE and 4.4 percent for Lenovo. Ascend P2HuaweiHuawei smartphoneShare0	cc/2019-30/en_head_0044.json.gz/line3329
__label__wiki	0.56449	0.56449	Working horse weekend at Beamish Open air museum near Stanley stages equine celebration this weekend By Bruce Unwin Chief Reporter (Durham) HORSE-LOVERS are urged to canter along to the region’s open-air heritage museum this weekend for an equine extravaganza. Fifty horses and an array of horse-drawn vehicles will be on show at Beamish, The Living Museum of the North, near Stanley, County Durham. The museum’s Horses at Work event, tomorrow and on Sunday, will feature pit ponies, elegant carriage horses and heavy horses, ranging from Irish Draughts and Friesians, to Shires and Clydesdales. There will be a colourful parade on both days, while visitors will have the chance to take a trip on a variety of horse-drawn vehicles, including two late 1800s London omnibuses. Some of the equine stars will perform in displays, but there will also be the opportunity to meet the site’s pit ponies and take part in several fun, family activities. Paul Foster, Beamish’s historic events officer at Beamish, said: “Horses at Work will bring together a unique line-up of 50 horses and horse-drawn vehicles, including two Victorian omnibuses. “We’re looking forward to an exciting weekend, with lots to see and do!” The theme for this year’s Horses at Work weekend is homecoming, reflecting the transition from conflict and the return to peacetime after the end of the First World War. During the weekend there will be the chance to see members of the Durham Pals brigade arriving back at Rowley Station with a celebratory homecoming parade. Led by the Borneo Band, and featuring an Armstrong Whitworth replica car, soldiers and several horse-drawn vehicles, the parade will travel from Rowley Station to the museum’s 1900s Town, at 1pm each day. A welcome home speech will be given outside the Masonic Hall to mark the troops return. Visitors will be able to find out more about the North-East War Memorials project, with a display in The 1900s Town’s Bank Board Room, on Sunday. In the 1900s Pit Village, the 16th Lancers Cavalry Unit will be on parade, while pit ponies can be seen demonstrating how tubs of coal were hauled, alongside other harnessed ponies, outside the pit pony stables. In Hetton Silver Band Hall, visitors can find out more about the work of the Brooke charity, set up in 1930 by Dorothy Brooke to help ex-war horses, and still now dedicated to the welfare of working horses and donkeys. A pack horse will be on show at the 1820s Pockerley Old Hall, while watch teams of horses will perform field work and land cultivation nearby. Chris Thompson, Beamish’s keeper of animals and land engagement, said: “During the First World War, horses helped keep the country going on the Home Front, as demonstrated during our Horses at War 2018 event. “When the war ended, men needed to slot back into society, and horses had to do the same, so this is the story we’ll be telling this year during Horses at Work.” Admission is covered by the general Beamish entry fee and is free for holders of unlimited passed and Friends of Beamish members. The museum, just off the A693, is open daily from 10am to 5pm, with further information available via www.beamish.org.uk. Old picture postcards of County Durham railway stations Definitive proof that ghosts really do exist in Ferryhill Do you remember lemonade pop brewer Grays of Spennymoor? Knit Aid: Why Bob Geldof wore a woolly woodlouse jumper in Darlington Top 10 most curious bridges, including one built by God Allegiances of blood were formed in the Battle of Marston Moor The eccentric widow of Lartington Hall who lived with her one-eyed parrot under an umbrella as the mansion crumbled around her The history of Witton Park controversially closed bridge Pictures: The construction of Darlington's inner ring road	cc/2019-30/en_head_0044.json.gz/line3330
__label__wiki	0.550293	0.550293	Spelman Receives One of the Largest Single Donations to an HBCU in History Anne Branigin Filed to: HBCUFiled to: HBCU HBCU donations HBCU donors HBCU endowment Ronda Stryker William Johnston Center for Innovation and the Arts Thanks to a massive $30 million donation from a trustee, Spelman just recorded its largest single gift from a living donor. The donation—among the highest given to any historically black college or university—will go toward the private women’s college’s new Center for Innovation and the Arts. As the Atlanta Journal-Constitution reports, the donation was made by Ronda Stryker and her husband, William Johnston. Stryker, a Spelman trustee for more than 10 years, heads the Stryker Corp., a Fortune 500 company specializing in medical technologies. Her husband is the chairman of investing banking firm Greenleaf Trust. The gift is significant, as the AJC notes, because HBCUs rarely receive the type of large donation that is typical of Ivy League schools and some of the larger, more affluent PWIs. For perspective, the University of Southern California once received a $200 million donation. Spelman’s largest single donation was $37 million—a gift from the estate of Readers Digest founder DeWitt Wallace. The difference gets even starker when you look at endowments. Compared to other HBCUs, Spelman’s endowment of $367 million is fairly substantial. Howard’s comes in at around $685 million. Morehouse—Spelman’s brother institution—has a $135 million endowment. But that number is just a fraction of New York University’s endowment of more than $4 billion. And even comparing Spelman against other historically female colleges, such as Vassar and Wellesley, that number still pales. Both of the latter schools boast endowments of just over $1 billion. Given historic issues with funding, these large donations are especially important to HBCUs. As Spelman President Mary Schmidt Campbell told the AJC, Stryker’s gift is “transformational.” “Her contribution ensures that Spelman students will be prepared to tackle the challenges of our changing world through innovation, creativity and the dynamic intersection of science, technology, engineering, arts and math,” she said. According to the AJC, the new center, expected to cost about $86 million, will house “all of Spelman’s arts programs – art, art history, curatorial studies, dance, digital media, documentary filmmaking, photography, music and theater.” This includes a number of venues and services the school hopes will draw in the Westside Atlanta community in which the college is nestled. This includes an expanded Museum of Fine Art, a digital theater, technology events, and a cafe, reports the AJC. White Student at HBCU Law School Antagonizes Her Black Classmates With Racist Comments The Black Renaissance Is Real: HBCUs See Record Growth in 2017 I Went to Morehouse College, But Morgan State University Was the First HBCU I Fell in Love With Staff writer, The Root. Sometimes I blog slow, sometimes I blog quick. Do you have this in coconut? Recent from Anne Branigin Police Arrest Suspect in Death of Baton Rouge Community Activist, Say No Evidence That Killing Was a Hate Crime On 5th Anniversary of Eric Garner’s Death, Protesters Will Take to New York City’s Streets Once More Rained Out by Hurricane Barry, Delta Sigma Theta Sorority Turns Canceled Convention Day Into Major Food Donation	cc/2019-30/en_head_0044.json.gz/line3332
__label__wiki	0.791754	0.791754	Elite move for Boro’s juniors Boro Juniors Martin Dowey Scarborough Athletic will be switching at least two of their junior teams into an elite league next season to boost progression in the club. Boro have confirmed that the newly-formed Under-10s and the Under-15s will make the switch to the regional Junior Premier League, which is played on a Saturday morning and, across the country, contains clubs like Birmingham City, Southampton and Doncaster Rovers. The club hope to have all of their junior teams playing in the set-up in future seasons. Director of football development Paul Exley said: “It is a league that sits in between grassroots and academy football, with a certain standard of referees and a certain standard of coaching. “The games are played like academy football over four quarters and it is more about the development of players rather than winning. “The most important thing for us is getting the youngsters playing football the right way. “There is a bit of travelling involved because it is a better standard of football, which is what we want for our young players. “We don’t want to be climbing up the leagues with the senior team, without the junior set-up following suit and progressing themselves. “It is all about stretching players and not doing the easy thing by staying where we are.” The club will have a trials day on June 2 for both teams, with any players in the age groups able to come down and try out. Exley is also underlining that players, if selected for these elite Boro teams, can still play for Scarborough & District Minor League clubs on a Sunday. He added: “At the moment we have two age groups confirmed, but we still have until June to add further teams to this. “We are happy that this will help the local league as well because it will mean that no teams are being taken out of those leagues on a Sunday. Former Middlesbrough ace Kian Spence ready to commit to Scarborough Athletic “It leaves Sundays free, so at Under-10 level, the youngsters can go and play for whoever they want to.” Boro are also looking for new coaches to boost their set-up at both the Under-10 and Under-15 levels. They would have to be at least Level One qualified. Anyone interested should contact Exley on paul.exley@seadogtrust.com	cc/2019-30/en_head_0044.json.gz/line3333
__label__wiki	0.79678	0.79678	Home / Northeast / Difficult balancing act Difficult balancing act Any attempt to converge national vision with people’s voices in this contested region must be negotiated carefully Rakhee Bhattacharya \| New Delhi \| April 22, 2019 9:10 am The completion of two strategic bridges — Dhola-Sadiya and Bogibeel (above) — over the River Brahmaputra was to gain people’s trust and attain electoral benefits. (Photo: IANS) The General Election has fostered public debate and hit its democratic parlance mostly on split opinions pertaining to national security and economic development. The patriotic excitement of millions strongly adhere to India’s national security while many more believe that loyal nationalism lies in creating an egalitarian system with basic socio-economic and human rights to millions who are still on the margin. Interestingly, this binary existed in the North-east for a very long time from the post-Partition period. As the colonial State carved out political boundaries on the geography of South Asia, this constructed space — the North-east of India — was mapped with a set of complex external orientations by dividing its contiguous geography and ruining its natural neighbouring relations. With natural neighbours turning into “strategic neighbouring nations”, this borderland became a subject of national security and geopolitics. The strokes of the political borders produced multi-layered deadlocks and isolation; and created economic underdevelopment and infrastructural asymmetry in the North-east. This precisely kept the region at the margin of the national economy but made it the focal point for national security with about 98 per cent of India’s international boundaries. The narrative began to change in the post-1990s with liberalisation and introduction of policies on the economic development of the North-east. This focus grew manifold in the last five years of the BJP government at the Centre with an incessant push to “transform” it into an “aspirational” region of India. This is a reversal of the earlier narrative of the North-east. Economic development is the core policy agenda for the region under India’s Act East Policy since 2014. In 2017, Niti Aayog — the government think tank — laid down a blue print for the region in its “Three Year Action Agenda” on sustainable development, infrastructure and transit connectivity, industry and global capital, and youth. It was to “augment national wealth” and provide first-hand livelihood and economic opportunities to its people. This Action Agenda therefore proposed some special and region-friendly industries including sericulture, floriculture, tea plantations; silk and handicraft industries through centrally sponsored schemes. Henceforth development projects of the region became 100 per cent centrally funded against the 90:10 ratio earlier. That increased fund utilisation in the Northeast significantly, by 21 per cent in the last three years. Promotion of these specific sectors is linked with the idea of surplus economy, cash cropping and monetisation of indigenous knowledge, which can gradually transform the aspirations of the people and add higher economic values. The Action Agenda also proposed modernising the existing and new vocational and industrial training institutions through skilling. This is to support them to integrate their local economies and traditional knowledge systems to the larger markets, to become selfreliant, and to “remove the economic challenges of the region by removing economic and physical barriers”. In the backdrop of the Centre’s Act East Policy and its message of economic development for the region, the central budgetary allocation for the Northeast has increased by 21 per cent amounting to Rs 58,165 crores for the financial year 2019-20. The policy shift has also attempted to address the region’s geographical isolation by creating massive connectivity infrastructure. That is also to utilise the geography of the North-east for increasing trade volume, and ensuring mobility and a larger market in the long run. This push with respect to infrastructure projects has a manifold purpose of generating future geo-economics of the region, boosting defence logistics across its bordering areas, and gaining people’s confidence at large to make robust political capital. There has been a tremendous effort by the Centre to showcase the sincerity behind such moves and in the last five years, the completion of two strategic bridges — Dhola-Sadiya and Bogibeel over the River Brahmaputra —were to gain people’s trust and attain electoral benefits. Laying out such a clear vision for development in the region has helped the BJP form governments in six of the eight North-eastern states. The party expects to gain more in the current Lok Sabha election. After all there are 25 constituencies in the region with Assam alone accounting for 14. Leaving aside electoral politics, this development vision was imperative for the people of the North-east, who have been desperately in need of livelihood and other economic opportunities. Other than infrastructure deficit, the region is trapped in various human security challenges, and poverty possibly tops the list. The poverty ratio in the North-east has shown an alarming increase in the post-liberalisation period. About 33.61 per cent of the people in the region were below the poverty line even in 2009-10 against 29.61 per cent in India (Planning Commission figures). This figure came down marginally to 28.39 per cent in 2011-12 with National Sample Survey Office data modification but remained much higher than the national average of 21.92 per cent. There are about 13.2 million people in the region who are trapped in the vicious poverty circle. The situation is worst in conflict-ridden states like Manipur and Assam. Some regions of these states have poverty ratios ranging between 50 to 70 per cent (NSSO data). Unlike India’s overall situation where economic growth could ensure redistribution policies in the post-liberalisation period and could address poverty issues substantially, its borderland states in the North-east sunk into an even greater poverty-trap despite the fact that its formal economy has also grown from Rs 96,855 lakh in 200405 to Rs 37,8221 lakh in 2015-16, which is about four times increase in volume (Central Statistics Office data). This increase, possibly, has not made any structural change in the economy of the region to uplift its people from such a severe poverty-trap. The data of the organised industries may reveal the truth partially. Such industrial sectors, which can absorb increasing workforce, for example, have just doubled their units from 2,211 in 2004-05 to 5,096 in 2015-16. The number of people engaged in these industries has also just doubled from 142,633 in 2004-05 to 278,149 in 2015-16 (Annual Survey of Industries data). Thus most of the employment outside agriculture is in the low productivity unorganised sector. The unemployment rate was highest in India in one of the states in the region, Tripura with 25 per cent followed by Nagaland at 23 per cent (NSSO data, 2011-12), adding substantially to India’s jobless growth and driving out a large number of youngsters from the region in search of livelihood and education to other parts of the country. Economic under-performance, a high poverty ratio, lack of livelihood opportunities and infrastructural deficits have augmented conflicts in some states of the region, creating a very high intra-regional disparity with Manipur as the “poorest” and Sikkim as the “richest”. The current proactive Centre has a long-term vision to not only “transform” the narrative of marginality of the North-east, but also to integrate it into the dominant national economy with large scale development where free flow and economic mobility can help to empower its people. This seems to be an exciting proposition to many, but given the sensitivity, complexity and diversity of the North-east, a section of people think that economics would override the ground realities and snatch various indigenous rights. Glimpses were already shown in the recent past when the region became a fresh site of resistance against the Citizenship Amendment Bill and said no to the ruling party at the Centre, proving once again that the issue of identity in this region “cannot be compromised for economic development alone”. Therefore any attempt to converge national vision with people’s voices in this contested region must be negotiated carefully, which otherwise can easily make it volatile. However, the verdict of the General Election will soon let the nation know about the minds of the people of the North-east on such transformative developmental ideas of the Centre. (The writer is on the faculty of Jawaharlal Nehru University, New Delhi) Act East policy BJP government Bogibeel Bridge Hope India raises its 1st international sovereign bond in London: Theresa May DUKPA, the vanishing TRIBE Landslides block two highways in Kalimpong district	cc/2019-30/en_head_0044.json.gz/line3334
__label__wiki	0.830286	0.830286	Sergei Romaniuk Historian who wrote acclaimed books on the prerevolutionary buildings of Moscow that were wrecked by the Soviet regime October 15 2015, 1:01am, The Times Romaniuk discovered that 53 Arbat was once the home of the poet Alexander Pushkin and his bride Nataliya Sergei Romaniuk was the foremost historian of Moscow’s buildings and the people who inhabited or commissioned them. He was an authoritative voice on the city’s rich built heritage, much of which was vandalised or destroyed after the Russian revolution. He wrote more than a dozen acclaimed books on the city that restored its pre-1917 architectural treasures to their proper place in Moscow’s history. Typical of the architectural historian’s fine detective work was his discovery in 1984 of an 1831 document that confirmed that a beautiful neoclassical house, No 53 Arbat, had once been rented by the poet and playwright Alexander Pushkin, who lived their for with his bride, Nataliya. After this discovery, the building was transformed into the house-museum of Pushkin. A tall, handsome man…	cc/2019-30/en_head_0044.json.gz/line3336
__label__wiki	0.982151	0.982151	Stagecoach books its seat as Spanish group raises bid for National Express Nic Fildes and Miles Costello September 4 2009, 1:00am, The Times The Spanish-led consortium bidding for National Express has increased its offer for the troubled transport operator to £765 million and struck a separate deal to sell its UK bus and rail divisions to Stagecoach. Spain’s Cosmen family, the largest shareholder in National Express with an 18.6 per cent stake, and CVC Capital Partners, the private equity group, have raised their offer to 500p a share — more than 10 per cent higher than the bid rejected by the National Express board last week. The offer, described as final, is conditional on receiving a recommendation from the board. The consortium said: “The offer provides the opportunity to draw a clear line under the recent difficulties associated with the company’s UK rail franchises, relations with the Department…	cc/2019-30/en_head_0044.json.gz/line3337
__label__wiki	0.915781	0.915781	JK Rowling Trolled by Piers Morgan on ‘Harry Potter’ 20th Anniversary Media personality accuses author of “conning the easily mesmerized masses” with “execrable literary hogwartwash” Tim Kenneally \| June 26, 2017 @ 10:42 AM Happy anniversary, J.K. Rowling. By the way, Piers Morgan is peeing all over your parade. Media personality and social-media curmudgeon Morgan took aim at Rowling on Monday, the 20th anniversary of the publication of the first “Harry Potter” book. Morgan’s pot-shot took place after Rowling posted a tweet marking the anniversary. Also Read: Harry Potter Turns 20: JK Rowling Thanks Fans on First Book's Anniversary “20 years ago today a world that I had lived in alone was suddenly open to others,” the author wrote. “It’s been wonderful. Thank you.” A pleasant, innocuous message in the eyes for many, perhaps, but for Morgan, it was an opportunity to pounce. “20 years of conning the easily mesmerized masses with execrable literary hogwartwash. Congrats,” Morgan spat back across the sandbox of social media. Also Read: There Are Actually Two Harry Potters, J.K. Rowling Reveals For emphasis, Morgan added an emoji of a face seemingly about to vomit, along with a thumbs-down symbol. Morgan’s expression of ill will earned him plenty of detractors in the comments section of his tweet. “What a mean thing to say,” wrote one critic of Morgan. Also Read: Piers Morgan on Amber Rose's Exposed Crotch: 'This Is Not Feminism' “He couldn’t write f–k in the dust of a venetian blind (to quote Coral Browne),” another commenter said of Morgan. “Piers, can you not be gracious with anyone you have a conflict with? Are you that bitter? She’s got to you, hasn’t she?” wrote yet another Morgan critic, who added, “She has bigger balls than you Piers with getting to where she is today. Not too difficult I hear.” 20 years of conning the easily mesmerised masses with execrable literary hogwartwash. Congrats. ??????’? https://t.co/x2493DvvJK – Piers Morgan (@piersmorgan) June 26, 2017 Harry Potter: 15 Magical Facts About JK Rowling's Beloved Boy Wizard Franchise (Photos) J.K. Rowling launched Pottermania on June 26, 1997 with the publication of "Harry Potter and the Philosopher's Stone" (retitled "Sorcerer's Stone" in the U.S.) and four years later a film version began a decade-long franchise that was just as successful. TheWrap teamed up with IMDb to give you these 15 facts you may not have known about the film series. The roots of the Potter films begin in 1997 with David Heyman, the man who has produced every installment of the series including "Fantastic Beasts." Heyman was looking for a young adult book series to pitch to the major studios, and received a copy of "Sorcerer's Stone" from his assistant. Two years later, Rowling sold the rights to her books to Warner Bros. for $2 million, on the condition that only British actors be cast. One major exception to this was Dumbledore's original actor, the Irish-born Richard Harris. He repeatedly turned down the role because he did not want to commit to filming several sequels, but eventually relented for his Potter-loving granddaughter. Sadly, Harris passed away in 2002 after filming "Chamber of Secrets," and was replaced by Michael Gambon. Part of the appeal of the Potter films has been watching Daniel Radcliffe, Emma Watson and Rupert Grint grow up with their characters, but that almost didn't happen. While looking for a director, WB considered Steven Spielberg, who wanted to do the films as an animated series that combined the books together. WB president Alan Horn vetoed the idea insisting the films be live-action. Having only written four of the books at the time filming started, Rowling was brought on as a creative consultant to make sure the movie did not contradict her plans for the remainder of the series. To this end, she revealed plot elements she had not yet written to Alan Rickman, whom Rowling had hand-picked to play Snape. This included the reveal of Snape's love for Lily Evans from the climax of "Deathly Hallows." Fans might remember protests against Pottermania from conservative Christian groups who claimed the franchise promoted pagan witchcraft. These had an impact on the filming of "Sorcerer's Stone," as requests to shoot at Canterbury Cathedral were blocked. Instead, the Dean of Gloucester welcomed the crew to film at his cathedral, saying that he was a big fan of the series. Creative Commons/Mattana Director Chris Columbus aimed to film as much of "Sorcerer's Stone" on-location as he could. While later films used more studio shooting, it was shot at major sites in England including King's Cross, Durham Cathedral and Alnwick Castle. The major exceptions were the Gryffindor common room and the Great Hall, which were filmed in-studio. In both the books and the film, Platform 9 3/4 isn't really between platforms 9 and 10 at King's Cross. Platforms 9 and 10 are suburban platforms located in a rather mundane-looking part of the station, while the grander area seen in the film and depicted in the books is the inter-city area located on platforms 4 and 5. Still, if you go to King's Cross and find the real platform 10, you'll find nearby a sign for platform 9 3/4, featuring a luggage cart disappearing into the wall. When casting for The Boy Who Lived, Columbus was bent on getting Daniel Radcliffe for the role after seeing him in the 1999 BBC adaptation of "David Copperfield." It almost didn't happen, though, as Radcliffe's parents were afraid that he would be overwhelmed by the media attention. After a long talk with Columbus and Heyman, they eventually agreed. Rupert Grint's audition was completely different. To get the role of Ron Weasley, he sent in a videotape of him rapping about why he should be in the movie. In 2011, during a panel for "Deathly Hallows," he performed a part of his rap for a crowd of Potter fans. Even today, the differences between Radcliffe and Grint are striking. While he's racked up over $95 million from his time playing Harry, Radcliffe admitted in a 2016 interview with The Telegraph that he's barely spent any of it. Grint, meanwhile, spent his money on fulfilling his childhood dream of owning an ice cream truck. TheWrap As for Emma Watson, she was reluctant at first to audition for Hermione, but was convinced to do so by her Oxford theatre teacher. She got the part after Heyman and Rowling were impressed by her confidence during screen tests. In an attempt to remain as faithful to the books as possible, Watson was originally given fake teeth to match Hermione's buck-toothed smile from Rowling's descriptions. They were scrapped after Watson struggled to speak with them. J.K. Rowling herself was offered a cameo in the film as Harry's mother, Lily, who appears in the Mirror of Erised. Rowling declined, and the role was given to Geraldine Somerville. The floating candles in the Great Hall were created with a special effects rig that moved the candles up and down in special holders that created the illusion that they were floating. That rig was scrapped in the sequels after one of the wires snapped and dropped a candle. No one was injured, but it was decided that the candles would be entirely computer generated in later films. While most movies are not filmed in chronological order, Columbus decided to film most of "Sorcerer's Stone" starting from the beginning to help Radcliffe, Watson and Grint come together as a group. One of the few exceptions to this was the Quidditch match, which was filmed last due to the high amounts of special and visual effects. Go to IMDb for more trivia, goofs and quotes. Here’s some trivia you may not have known about how J.K. Rowling’s beloved books became a film franchise Harry Potter: 15 Magical Facts About JK Rowling’s Beloved Boy Wizard Franchise (Photos) By Jeremy Fuster \| November 17, 2018 @ 4:40 PM Harry Potter Turns 20: JK Rowling Thanks Fans on First Book’s Anniversary By Thom Geier \| June 26, 2017 @ 4:10 AM There Are Actually Two Harry Potters, J.K. Rowling Reveals By Carli Velocci \| June 23, 2017 @ 10:38 AM	cc/2019-30/en_head_0044.json.gz/line3339
__label__cc	0.713847	0.286153	Painted as the Bad Guy An ominous looking man sits on a park bench, dressed in villain-like attire, seemingly on the verge of committing a crime. Nigel had been painted as the bad guy. There used to be a cartoon by United Artists called Roland and Rattfink. It featured a stereotypical hero and villain. It was sometimes shown as a part of The Pink Panther series. The hero, Roland was a Canadian Mountie and had a prominent chin, while the antagonist, Rattfink (not to be confused with Batfink (a hero from a different cartoon)) was dressed in all black with sinister moustache and full of malevolent intent. I think he would have to be my largest inspiration for this drawing. …well, him and Dick Dastardly of Hanna-Barbera origin. Dick Dastardly was probably better known because of his off-sider canine called ‘Muttley’ who had a seriously wheezy laugh. For the sake of trivia, and going off on a tangent now, there was another cartoon dog, going by the name of Precious Pupp, who had an identical laugh to that of Muttley. Anyway, back to Nigel… I chose Nigel as a name because Nigella is a girl’s name. I liked the idea of having him be the only coloufully rendered section of the drawing, with the foreground and background being simple lines and plain white for contrast. Initially he was in flat colour, but I’ve tried to give him a textured, painted look, though it’s not so easy to tell at the size shown here. Similarly, I’ve tried to give him a sinister expression and the fact that he’s holding an explosive plunger is a tell-tail sign that he’s up to no good. My apologies for the delay with this posting. I’ve been working on a website make-over, which hopefully I will be able to apply in the not too distant future. In Cartoons, General antagonist bad guy bad guy on park bench bad painting cartoon hero line drawing muttley painted painted as the bad guy precious pupp roland and rattfink villain	cc/2019-30/en_head_0044.json.gz/line3340
__label__wiki	0.625335	0.625335	Grown Up Magic Writing For Teens Vs. Adults: Rowling As Case Study What does Salman Rushdie’s new memoir, Joseph Anton, and J.K. Rowling’s The Casual Vacancy tell us about writing for children versus adults? Professor Seth Lerer on why one author’s approach of switching back and forth works, and the other fails. Seth Lerer Updated 07.14.17 1:00AM ET / Published 10.03.12 12:46PM ET Anthony Devlin, Press Association / Landov Midway through Salman Rushdie’s memoir of his life under the fatwa, Joseph Anton, the beleaguered novelist reflects on those books and movies that had filled his childhood. Of The Wizard of Oz, he notes, “the two great themes of the film were home and friendship.” Home and friendship are the themes not just of Joseph Anton, but all of Rushdie’s work: novels and stories, essays and reflections about how the world of childhood morphs from magical remembrances into the everyday reality of adult life. Home and friendship, too, are the themes of all great works of literature, whether for children or adults: the novels of Charles Dickens, the tales of Mark Twain, the narratives of Toni Morrison, and, indeed, the Harry Potter books of J. K. Rowling. Rushdie’s Joseph Anton and Rowling’s The Casual Vacancy, released within a week of each other, challenge us to ask: what is the place of childhood in the adult world; what happens when a writer turns from young to grown up readers, and from adult themes to children’s entertainment; what do we expect from our writers, and what happens when they disappoint us? Many readers came to Rushdie’s book expecting personal confession or contrition, or a deep reflection on the writer’s life in a politically charged world. They got that, but they got it colored by a distancing, third-person narrative and bouts of self-justification. Many readers, too, will come to J. K. Rowling’s novel for adults expecting the prose wizardry of Harry Potter. Will they be disappointed? Harry Potter was a brilliant achievement. It blended the coming-of-age story, inspired largely by Dickens, with the magical wonders of Tolkien. Most children read the books for their excitement. I read them for their literate lessons. In Harry Potter, the true wizardry went on not in the forest or the playing field, but in the classroom and the library. Wizardry was but a heightened form of literacy: a way of reading recipes and of reciting spells. Harry Potter’s is a world of books, and the stories got young people reading not just because they were interested in the plots or characters, but also because the very lesson of the books was to read books themselves. Home and friendship were defined by what was on the bookshelf and who shared your readings. Hogwarts was a place of shared belonging, poring over textbooks, rooting through the library, and finding peers among the paperwork. The Dursleys' home, by contrast, was a place of isolation, as Harry can only read alone, buried under the bed sheets. After all of this magic, what could we have expected? The Casual Vacancy may be a disappointment, but it is a natural one. For after having written books of magic for a magical age, Rowling has come out with a book of Muggle life for Muggles. Is this what happens when you grow up? Do we leave behind the thrills of a Dickensian adventure for the ordinary evenings of a small town’s politics? Do we abandon David Copperfield or Great Expectations and grow up to live in the novels of Anthony Trollope? After all of the adventures at Hogwarts, Rowling may be saying, all you want to do is snuggle up with a cup of tea and a vicar. We may believe that she has let us down; but maybe we have let ourselves down, too. Unlike the Hogwarts students, the adults who populate the Pagford of The Casual Vacancy (and so many of our own towns) are not readers. They do not ride into imagined worlds; they do not fill their lives with books. The conflict of the novel hinges on competing institutions: a public housing project and an addicts’ clinic, the former a faceless block of living spaces, the latter a hospital for those who tried to escape them. In a world without books, there are only drugs. The potions of Hogwarts had their narcotic effect, but for the children who came back to read Harry Potter again and again, the addiction was to words. Among the novel’s characters—Barry Fairbrother, Howard Mollison, Krystal Weedon, and a host of evocatively named others—the only one who could be said to have a truly inner and imaginative life in the novel is the troubled young Krystal: living in the projects, a bit of crystal in the weeds. Only here will readers of the novel find a fully interiorized life. Only here will readers find a level of prose that aspires to literary fiction. “Fear fluttered inside Krystal’s belly like a fetus.” Not bad, and even better, too, is the extended passage in parentheses that charts the workings of her fears, with the parentheses themselves marking these paragraphs like stream-of-consciousness reflection. And yet, even Krystal has her troubles with the written word. Looking at the signage at a bus stop, she pauses. “Krystal did not read well; being confronted with large quantities of words made her feel intimidated and aggressive.” This moment in the novel seems to be its turning point: a damning statement about what it means to be functionally illiterate. Surely, the children and the teens who lapped up the hundreds of pages of Harry Potter were hardly intimidated by large quantities of words. And surely Hermione Granger was hardly put off by the kinds of signs that anger Krystal: “line upon line of impenetrable print, with words as long as Krystal’s arm and arrows pointing left, right, diagonally.” It is as if, here, in this all-too-Muggle world, a young girl cannot face the enigmas of writing, as if the bus-station sign becomes a potion or a cryptogram, as if she cannot transport herself out of this sad space, with its diagonal arrows, into a magical Diagon Alley. Perhaps that, too, is Rowling’s dilemma. For having trapped us on an ordinary street, she does not have the words to lift her characters to inspiration. This never was a problem for Rushdie, who has moved effortlessly between writing for adults and writing for children. Haroun and the Sea of Stories grows out of the magical realism of Midnight’s Children. Joseph Anton itself begins with one of the most affecting remembrances of a father’s powerful, and powerfully ambivalent, legacy. What Rushdie realizes is that, in the end, all readers become children when led by the hand of a great writer. Dickens knew that in David Copperfield (as much an influence on Midnight’s Children as any lived experience of India). At the start of that novel, the young David finds himself in his late father’s library, and reading the adventures of Tom Jones, Don Quixote, and Robinson Crusoe his imagination is kept alive. “I had a greedy relish,” he recalls, for stories, and he looks back on his time in the library, “reading as if for life.” Without such reading, there can be no life, and it seems to me that the real vacancy, casual or otherwise, in Rowling’s novel is the book itself. Home and family can give us fair brothers. But only the literate imagination can bring them back to life.	cc/2019-30/en_head_0044.json.gz/line3343
__label__wiki	0.875449	0.875449	Business Commentary Know your limit: The Canadian copyright review in the age of technological disruption Know your limit: The Canadian copyright review in the age of technological disruption MICHAEL GEIST Special to The Globe and Mail Published December 21, 2017 Updated December 21, 2017 Michael Geist holds the Canada Research Chair in internet and e-commerce law at the University of Ottawa, Faculty of Law. He can be reached at mgeist@uottawa.ca or online at www.michaelgeist.ca. The Canadian government launched its much-anticipated copyright review last week, asking the standing committee on industry, science and technology to conduct a study on the issue that is likely to run for much of 2018. While the timelines suggest major changes will have to wait until after the next election, the report will be the foundation for future reforms to Canadian copyright law. The instruction letter to the committee from Innovation, Science and Economic Development Minister Navdeep Bains and Canadian Heritage Minister Mélanie Joly points to the challenges of copyright, which invariably engages a wide range of stakeholders with differing perspectives. Indeed, Mr. Bains and Ms. Joly note in their letter that "this diversity of viewpoints is because copyright affects a wide range of industries, works, and uses: from telecom and tech companies, to scientific institutions, and academia, from photographs, music, and books, to augmented reality content; and from museums, art galleries, and brick and mortar stores, to machine-readable data, and beyond." Reconciling such a broad range of interests with a law that affects all Canadians is exceptionally difficult. The letter touches on everything from compensation for artists to the public domain and open access, but the most important passage may well be the recognition that while market disruption often drives copyright reform, the law may not always be the best tool to address the current state of technology-driven change. The ministers note that many issues fall outside the scope of the law, suggesting that efforts to use legal tools to impede changing dynamics in the marketplace may ultimately harm the very stakeholders the law is intended to assist. In fact, the top-line issues for many of the traditional stakeholders in the copyright debate are largely grounded in the view that technological disruption requires a legislative response based on copyright law. For example, publishers and authors have been lobbying the government for several years to roll back the rules on "fair dealing," Canada's version of fair use. The Supreme Court of Canada has said that fair dealing – which allows for the use of portions of works without further permission or licence – is a user's right. The groups point to declining revenues from a licence offered by Access Copyright, a copyright collective, as evidence of the problem. Yet the publishing and education sectors represent a classic case of technological disruption. Since the 2012 copyright reforms, the publication of new Canadian titles has not declined, and educational spending on licensing works from publishers and authors has increased as the sector shifts from buying physical books and paying for collective licences to licensing e-books and access to massive content databases. Many universities today, including my own, licence more than a million e-books, many with perpetual licences. This means that even as some publishers and authors express concern about educational copying, they earn new revenues from digitally licensing their works to educational institutions. Disruption is also a theme in music-industry lobbying, which claims there is a gap in the revenues earned from internet music streaming and the value of that music. Yet, a closer look at the numbers points to an industry earning record revenues from new technologies and the internet. The days of worrying whether consumers would pay for music are largely over, with the Canadian music market growing much faster than the world average (12.8 per cent in 2016 compared with 5.9 per cent globally), streaming revenues more than doubling last year to $127.9-million (U.S.) – up from $49.82-million – the Canadian digital share of revenues of 63 per cent exceeding the global average of 50 per cent and Canada leaping past Australia to become the sixth-largest music market in the world. Virtually every cultural sector has similar stories. Since the 2012 copyright reforms, music collective SOCAN has experienced a tenfold increase in internet-streaming revenues, with growth rates of more than 100 per cent over the past year alone, but it is still calling for an extension of 20 years to the current international standard term of copyright, the creator's life plus 50 years. Movie theatre and overall broadcast revenues have continued to increase since 2012, but that has not stopped some in the industry from demanding new website-blocking rules. Many media organizations have struggled with the transition to digital, leading to the hope that a new "link" tax could be added to copyright law that would require compensation merely for linking to a work. That approach might provide some incremental revenue, but would undermine valuable referral networks that increase website traffic and support digital advertising earnings. The 2012 copyright reforms ushered in innovative changes, including legal protection for user-generated content, the notice-and-notice system for online infringement allegations, which enables rights holders to educate users on the boundaries of copyright, and some of the world's toughest anti-piracy rules. The five-year review offers the chance to take stock of those amendments and chart a course for future policies. In doing so, the committee should ensure it opens the process to all Canadians and keep the ministerial admonition on the limits of copyright law in an ever-changing, disruptive marketplace very much in mind. Canada’s intellectual property strategy must play to the country’s strengths Why copyright law poses a barrier to Canadian AI ambitions Canada is now home to some of the toughest anti-piracy rules in the world Follow us on Twitter @globeandmail Opens in a new window We have closed comments on this story for legal reasons or for abuse. For more information on our commenting policies and how our community-based moderation works, please read our Community Guidelines and our Terms and Conditions.	cc/2019-30/en_head_0044.json.gz/line3348
__label__wiki	0.945895	0.945895	New South Wales politics NSW to change laws to allow child abuse survivors to sue churches Berejiklian government says laws will allow thousands to seek compensation Sun 10 Jun 2018 00.19 EDT Last modified on Sun 10 Jun 2018 00.27 EDT Survivors of child sexual abuse will be able to sue churches under changes to New South Wales’s civil litigation laws proposed by Gladys Berejiklian’s government. Photograph: Tracey Nearmy/AAP Survivors of child sexual abuse will be able to sue churches and other institutions under changes to New South Wales’s civil litigation laws. The state’s attorney general, Mark Speakman, on Sunday said the state government would remove legal barriers that have stopped victims from seeking justice, based on recommendations from the royal commission into institutional child sexual abuse. “These reforms will provide access to new avenues to allow survivors to pursue compensation so they can focus on recovering and moving forward with their lives,” he said. Child sexual abuse: all states on board for redress after WA resolves doubts Under the changes, institutions would also no longer be able to distance themselves from the actions of so-called “non-employees” such as volunteers and paedophile priests. The NSW government said it would reverse the onus of proof and require organisations to prove they took reasonable precautions to prevent abuse. Under the current laws, a church cannot be sued because it does not legally exist as its assets are held in a trust. This known as the “Ellis defence”. Courts will now have the power to appoint trustees to be sued if those institutions fail to nominate an entity with assets and allow the assets of the trust to be used to satisfy the claim. More than a decade ago, the Catholic Church won a legal battle against former altar boy John Ellis, who was sexually abused by Father Aidan Duggan of the Bass Hill Parish when he was 13. Ellis sued the priest, along with Cardinal George Pell and the trustees of the Roman Catholic Church for the Archdiocese of Sydney. The supreme court trial judge found the trustees could be sued but the court of appeal ruled the trustees did not control nor was responsible for Duggan’s conduct. Duggan died in 2004. Ellis said the new laws were the “culmination of a life’s work” and would ensure survivors would not face the same setbacks as he had. Speakman said the laws, which were drafted in response to the royal commission’s redress and civil litigation report, would enable “thousands of survivors” to seek compensation. Victoria passed laws to close the legal loophole in May. NSW hopes to introduce them in parliament before the end of 2018. “It’s staggering that these institutions in the past have been abject failures when it comes to reporting what has gone on,” Speakman told reporters. “These reforms will make it easier for child sexual abuse survivors ... to take action against those who have failed them in the past.” The Catholic Church in NSW said it had been helping survivors to identify proper defendants and ensuring claims are met “for some time now”. “However, the NSW dioceses recognise more can be done to make access to the justice system easier,” Sydney archbishop Anthony Fisher said in a statement. “We support having a clear entity as a proper defendant for claims.” Royal commission into institutional responses to child sexual abuse	cc/2019-30/en_head_0044.json.gz/line3349
__label__wiki	0.805151	0.805151	Defence and security blog 70 years after Hiroshima, nuclear weapons threaten us all Nuclear weapons are an austerity-free zone Richard Norton-Taylor Thu 23 Jul 2015 08.38 EDT Last modified on Thu 11 Aug 2016 19.31 EDT On August 6, 1945, an atomic bomb instantly destroyed almost all of the houses and buildings in Hiroshima. Photograph: Stanley Troutman/AP Nearly 70 years ago, on 6 August 1945, the US dropped “Little Boy”, the first nuclear weapon used in warfare, on Hiroshima. “Two thirds of the buildings in the city were destroyed and perhaps 80,000 civilians were killed”, observes Eric Schlosser, in Gods of Metal, a frightening yet moving account of how three Catholic pacifists, including an 82 year-old nun, broke into Y12, a top security nuclear weapons base in Tennessee, known as the Fort Knox of Uranium, where material used in the bomb that destroyed Hiroshima was processed. “The amount of weapons-grade uranium needed to build a terrorist bomb with a similar explosive force”, Schlosser adds in his extremely timely short book, “could fit inside a small gym bag”. Though there are treaties banning biological and chemical weapons, cluster bombs, and landmines, there is no such ban on nuclear weapons, even though their use would breach international agreements, not least the Geneva Conventions. 70 years after Hiroshima, despite all the rhetoric and genuflection (and negotiations with Iran) moves towards global nuclear disarmament are further away than ever. Vladimir Putin brandishes Russia’s tactical nuclear weapons capability, presenting British ministers (and the Labour front bench) an excuse to spend £100bn-plus on a new fleet of four Trident nuclear ballistic submarines to provide a Continuous At Sea Deterrence (CASD). Yet David Cameron insists the greatest, indeed existential, threat to Britain, one the country will face for a generation, comes, not from any hostile state, but from violent Islamic extremists, notably Isis. Tony Blair said of Trident in his autobiography, A Journey: “The expense is huge and the utility … non-existent in terms of military use”. In the end he thought giving it up would be “too big a downgrading of our status as a nation”. (Of the Labour leadership candidates, only Jeremy Corbyn opposes Trident.) Sceptics describe nuclear weapons as “power tools”. Major General Patrick Cordingley, former commander of the 7th Armoured Brigade, the Desert Rats, says strategic nuclear weapons have no military use. “It would seem”, he said recently, “the government wishes to replace Trident simply to remain a nuclear power alongside the other four permanent members of the UN Security Council. This is misguided and flies in the face of public opinion; we have more to offer than nuclear bombs”. Britain continues to modernise its nuclear weapons arsenal. Though successive governments have reduced the stock, the UK still holds more than a hundred “operationally available warheads” . Without the cooperation of the US, concluded a report last year by the London-based Trident Commission, the life expectancy of the UK’s nuclear capability could be measured in months.The commission’s crossparty panel described Britain’s deterrent as “a hostage to American goodwill”. This year’s non-profileration treaty (NPT) review conference held under UN auspices in New York, took a step backwards on the road to nuclear disarmament, with the five “official” nuclear powers - the UK, US, Russia, China, and France - insisting on even vaguer language, and more caveats, than they have in the past. But the non-nuclear powers, the vast majority, are fighting back. 159 countries signed a statement at the end of the New York conference. “All efforts must be exerted to eliminate the threat of these weapons of mass destruction”, they said. “The only way to guarantee that nuclear weapons will never be used again is through their total elimination.” The statement referred to a “renewed resolve of the international community, together with the International Committee of the Red Cross (ICRC) and other organisations, to address “the catastrophic humanitarian consequences of nuclear weapons.” And more than a hundred countries have signed what they call a “humanitarian pledge”. It states: “the risk of a nuclear weapon explosion is significantly greater than previously assumed and is indeed increasing with increased proliferation, the lowering of the technical threshold for nuclear weapon capability, the ongoing modernisation of nuclear weapon arsenals in nuclear weapon possessing states, and the role that is attributed to nuclear weapons in the nuclear doctrines of possessor states...” Beatrice Fihn, executive director of ican (the international campaign to abolish nuclear weapons) told me: “The humanitarian initiative has enabled people to see nuclear weapons for what they really are, inhumane, indiscriminate and unacceptable weapons of terror.” One of the secret documents obtained by Edward Snowden in 2013 said US intelligence agencies had little “knowledge of the security of Pakistan’s nuclear weapons and associated material”. A classified US state department document released by WikiLeaks quotes a Russian foreign ministry official warning that Islamists “are not only seeking power in Pakistan but are also trying to get their hands on nuclear materials”. Schlosser warns: “There are still about 16,000 nuclear weapons in the world. Terrorists only need to steal one”. NPT review conference Labour party leadership	cc/2019-30/en_head_0044.json.gz/line3350
__label__wiki	0.971902	0.971902	Syrian government forces seal victory in southern territories Forces loyal to Bashar al-Assad take full control Daraa province - birthplace of 2011 protests that sparked civil war Kareem Shaheen in Istanbul Tue 31 Jul 2018 04.23 EDT Last modified on Thu 2 Aug 2018 12.40 EDT Smoke rising above buildings during airstrikes backing the Syrian government-led offensive in Daraa. Photograph: Jalaa Marey/AFP/Getty Images The Syrian regime has reclaimed a sliver of territory in southern Syria that was under the control of Islamic State, sealing its military victory in the strategic southern territories that rebelled in 2011 against Bashar al-Assad and fully reestablishing its hold over the frontier with the Israeli-occupied Golan Heights. The Syrian Observatory for Human Rights, a war monitor, said forces loyal to the Syrian regime had taken control of the last towns and villages in the province of Daraa that were under the control of Jaysh Khalid ibn al-Waleed, an Isis affiliate that controlled the Syrian part of the Yarmouk River basin, a tributary that runs through Syria, Jordan and Israel. The military victory in the area means Assad now fully controls the province of Daraa, the birthplace of protests in 2011 that spread throughout the country and challenged his family’s totalitarian rule. 'Their blankets are the sky': Syrian civilians flee Deraa The Assad regime, backed by Russian airstrikes, launched a campaign in mid-June to recover control of the southern and south-western parts of the country bordering Jordan and the Golan Heights – the provinces of Daraa and Quneitra. Rebel groups that had controlled most of the area for years quickly caved to the government’s advance after western backers including the US that had supported those fighters for years abandoned them and signalled they would not intervene to halt the regime’s offensive. Most towns and cities in Daraa and Quneitra capitulated in “reconciliation” deals that gave rebel fighters and civilians a choice between forced displacement to opposition territories in northern Syria or reconciling with the Assad regime. Most have chosen to stay, and some rebel groups joined the regime’s offensive against Jaysh Khalid ibn al-Waleed. Some humanitarian activists, including rescue workers who are part of the collective known as the White Helmets, remain trapped in parts of Daraa and Quneitra and have issued urgent appeals for their rescue. The Assad regime has reportedly refused to allow their evacuation, and the Syrian president has told a Russian media outlet that they would be killed if they did not lay down their arms. After rebel-held areas in Daraa and Quneitra were defeated, Assad’s forces went on to launch a bombardment of the Yarmouk River basin. That bombardment persisted despite an Isis attack on the neighbouring province of Sweida, which killed nearly 250 people. Isis militants also kidnapped 20 women and girls from the area and threatened to kill them if the regime continued its assault. Their fate is uncertain after the resumption of the campaign and the Isis defeat. The occupied Golan Heights is a plateau captured by Israel from Syria in 1967 in a move not recognised by the international community. Israel has maintained a close focus on the six-week campaign by Assad’s troops near the frontier and repeatedly said it will not tolerate Iranian forces approaching its territory as the battle concludes. Tehran has sent military staff and equipment to help Assad in the civil war and has built a significant presence in the war-torn state. Israel has responded with multiple airstrikes on bases where Iranian personnel are stationed. Israeli media reported that the government had asked Russia, also an Assad ally, to ensure government forces do not harm civilians near the perimeter fence, where displaced civilians have gathered in tents. The Guardian could not verify the report. Tensions between Iran and Israel peaked in February when Israel said it had shot down an Iranian drone in its airspace that had taken off from a Syrian airport. Since then, Israel has accused Iran of firing a barrage of rockets against its positions in the Golan. Additional reporting by Oliver Holmes in Jerusalem • This article was amended on 2 August 2018 because an earlier version said Isis militants threatened to execute, rather than kill, prisoners.	cc/2019-30/en_head_0044.json.gz/line3351
__label__wiki	0.819884	0.819884	Penguins Unite to Assist International Students Posted By: Jambar Contributor 752 Views By Nami Nagaoka As the population of international students at Youngstown State University increases each semester, the International Programs Office (IPO) started the United Penguins, a group dedicated to helping international students transition into life in the United States. Nathan Myers, the associate provost of the IPO, said he created the concept of the group two months ago. He said there were a couple problems that the IPO was trying to solve and there have been challenges associated with being an international student in the United States. “It was valuable for [international students] to be able to secure work experience and some small salary for students from an on-campus job,” he said. “By actually paying people to help make the community better and paying people basically to solve the problems that are actively faced by students every day, that might solve bigger problems not only providing people a job but also giving them experience in helping students in elevating their life while they are here.” He said they face difficulty meeting people, finding a place to eat and having transportation around the area. Myers said he lived on campus when he came to YSU for the first six months. He said it allowed him to live like a student and become aware of difficulties in living without any transportation. Myers said he saw a large group of new international students that were trying to walk to Walmart from 5th Avenue last semester. “No one should feel that there is a problem that cannot be solved, whether it’s a social problem or transportation problem,” Myers said. According to Myers, there were more than 90 applications for 15 open positions in United Penguins. United Penguins is divided into four teams: an activity team, a transportation team, a marketing team and a university life team. Fourteen United Penguins students leaders were selected by considering their grade, life experiences and other criteria. He said most of the positions are filled by students from different countries to help represent the perspective of their nationality. Ahmed Awad, a senior electrical engineering major, is the leader of the transportation team of United Penguins. He said he has been working for IPO since last summer. “I enjoy being a driver for IPO. It’s a good experience because I get to be with a group of people during all the activities,” he said. “It made me feel more connected to the new students around YSU.” He said he was not very active prior to being involved in the IPO even though he joined some social events. Meeting more people made him enjoy living in the United States more. Awad said United Penguins are more focused on international students. “People want to go where they feel like they belong. We hope international students will join us and we hope we can gather as much as we can so that we can all have a fun experience and time,” he said. Jiwon Mun, a sophomore biology major, is a member of the housing life team. She said she was looking for a job on campus for a long time. She applied for all of the positions that she was qualified for when a job opened at IPO last semester. “I wanted to get a closer relationship with IPO officers,” she said. “It was also for money, but I wanted to know about what is going on [among the international programs].” Mun started at YSU in the English Language Institute (ELI) in 2016. “I wanted to get to know new people at YSU not just my classmates,” Mun said. She said those experiences from her first years at YSU would help new international students. She said the United Penguins are friendly and open to everyone. There are team activities, which provides for collaboration within the international community at YSU. One thought on “Penguins Unite to Assist International Students” lance johnson says: Way to go Penguins! Being an international student away from home is difficult, compounded by our complex culture and language problems. Welcoming and assimilation assistance must come from numerous sources like the Penguins to aid these young people embarking on life’s journey. Most struggle in their efforts and need guidance from schools’ international departments, immigration protection, host families, concerned neighbors and fellow students, and even informative books to extend a cultural helping hand so we all have a win-win situation. Something that might help anyone coming to the US is the award-winning worldwide book/ebook “What Foreigners Need To Know About America From A To Z: How to Understand Crazy American Culture, People, Government, Business, Language and More.” Used in foreign Fulbright student programs and endorsed worldwide by ambassadors, educators, and editors, it identifies how “foreigners” have become successful in the US, including students. It explains how to cope with a confusing new culture and friendship process, and daunting classroom differences. It explains how US businesses operate and how to get a job (which differs from most countries), a must for those who want to work with/for an American firm here or overseas. It also identifies the most common English grammar and speech problems foreigners have and tips for easily overcoming them, the number one stumbling block they say they have to succeeding here. Good luck to all at YSU or wherever you study or wherever you come from, because that is the TRUE spirit of the American PEOPLE, not a few in government who shout the loudest!	cc/2019-30/en_head_0044.json.gz/line3352
__label__wiki	0.925651	0.925651	Member sign-in · Become a Member My account · Member sign-out Authentic European news, sourced locally Country editions: Jobs portals: Jobs in Austria Jobs in Denmark Jobs in Norway Jobs in Switzerland Austria Denmark France Germany Italy Norway Spain Sweden Switzerland Analysis: Has support for the Sweden Democrats peaked? election 2018 politics sweden democrats Sweden Democrats leader Jimmie Åkesson at the party's election night event. Photo: Lars Pehrson / SvD / TT Sweden's far-right had hoped to overtake the "establishment" in weekend elections and become the country's biggest party, but, having fallen well short of that goal, some are now wondering whether support for the Sweden Democrats has peaked. The anti-immigration party came in third, behind Prime Minister Stefan Löfven's Social Democrats and the opposition conservative Moderates, with 17.6 percent of votes, up 4.7 points from the 2014 elections. But that rise is smaller than the 7.2-point increase the party saw between 2010 and 2014, and far below the expectations of party leader Jimmie Åkesson, who, several hours before polling stations closed, said he was confident of winning "20 to 30 percent". It was also well below several opinion polls prior to the election, with the most favourable ones suggesting support around 26 percent. So was the election result a setback for the party? "Not at all," said Mattias Karlsson, head of the party's parliamentary group and its main ideologue. "All parties want to be as big as possible but we are the big winners of the election," he told AFP. After having largely underestimated the Sweden Democrats in previous elections, polling institutes overcompensated this time and overestimated them, he said. READ ALSO: What next for Sweden after election nailbiter? Mattias Karlsson speaking at the Sweden Democrats' election night event. Photo: Anders Wiklund/TT Yet the fact remains that they did not see the breakthrough they hoped for, and the seven other parties in parliament continue to ostracize the far-right and exclude it from discussions to form a new government. "Their core voters are white men from the working class, but they've broadened their electoral base, with more women, more immigrants and more people in big cities," says Anna-Lena Lodenius, an investigative journalist specializing in far-right movements. "They may still be able to climb by three or four points" and match the levels enjoyed by the far-right in other European countries such as Switzerland or Austria, she says. The Sweden Democrats are the biggest party among men, garnering 25 percent of all male voters. But they attract "only" 25 percent of working class voters and 15 percent of women voters. They also attract 15 percent of first-time and white collar voters. "We think we can still grow in some areas, like women, union members, voters of foreign background," said Karlsson, who on Monday wrote in a Facebook post that there were only two options ahead: "victory or death." While immigration and integration of immigrants played a big part in the election campaign, the far-right "ran up against a strong ideological counter-offensive" from the Greens and the ex-communist Left, as well as the Centre Party, a member of the centre-right Alliance, notes Linköping University professor Anders Neergaard. And the right-wing parties, the Moderates and Christian Democrats, also attracted some far-right supporters by adopting some of the Sweden Democrats' ideology -- at times using rhetoric verging on Islamophobic. READ ALSO: Will Swedish values survive the next two weeks? Risk of radicalization Generally, the far-right's geographical and sociological base is not spreading dramatically. "They're growing everywhere, but they're strong where they already were strong and weak where they are generally weak," such as the three big cities of Stockholm, Gothenburg and Malmö, notes Lund University political science professor Anders Sannerstedt. Two factors will likely influence the far-right going forward, experts suggest. Firstly, the party's position in parliament's balance of power the next four years; and secondly, whether Sweden will succeed in integrating the hundreds of thousands of asylum seekers it has taken in. "If they don't get the influence they want, there is a clear risk that they will radicalise ... Then they'll either grow or their voters will tire of them," Lodenius predicts. Should the left- and right-wing reach a cross-bloc cooperation to shut out the Sweden Democrats -- an idea currently being tossed around -- "they will be seen as the only opposition party," Sannerstedt adds. And if efforts to integrate immigrants were to yield better results, "immigration will be perceived as less problematic." But, he says, "there's nothing to indicate that that will be the case." The unemployment rate among foreign-born people is four times that of those born in Sweden. Meanwhile, the Sweden Democrats' success in municipal elections held the same day has left them short-handed. In their strongholds in the south, they won more mandates in local elections than they have candidates to fill seats. "People are subjected to a lot of threats, there's a strong social exclusion, in workplaces and unions. You lose friends or jobs, and that makes it hard for us to recruit people," says Karlsson. Despite its electoral success, "the Sweden Democrats remain a pretty hated party," Sannerstedt notes. By Gaël Branchereau Nine German words that strike fear into foreigners in Switzerland Family of Brit paralysed at Benidorm water park demand full investigation Italian police join FBI in raids on historic mobster families Merkel at 65: 10 photos that tell the story of Germany's 'eternal' chancellor What French women are looking for in a lover - according to their tweets From princes to undertakers - How Norway's motorists are going electric Northern European cities to be as hot as Australia by 2050, scientists say	cc/2019-30/en_head_0044.json.gz/line3354
__label__cc	0.743078	0.256922	Mahler: Symphony No. 5 (1/3) Antonio Martí Principal Trumpet at Charleston Symphony Orchestra (United States) » Antonio Martí in the Encyclopedia of Trumpet Players In this series of video lessons, Tony addresses the most important passages of one of the most sought after trumpet solos in auditions around the world. In this first lesson, starting at the beginning of the work, he gives us valuable advice on how to study, audition and perform the solo. Recording place Videolesson recorded in Albert Simons Center for the Arts at the College of Charleston, South Carolina (United States) in May of 2016 You must be logged in to view or purchase a videolesson. Please access your account or sign up here. Other related videolessons Subtitles: (n/a) Raymond Riccomini Imagery: Mahler’s Symphony No. 5 Benjamín Moreno Fábio Brum Preparation for an orchestral audition (2/2): Mahler’s Symphony No. 5 Subtitles: Spanish	cc/2019-30/en_head_0044.json.gz/line3359
__label__cc	0.57931	0.42069	TSW’s 4,000+ Acre Mixed-use Project RiverTown Breaks Ground Commercial Property News ran a story on RiverTown, a large mixed-use project just south of Jacksonville, Florida. TSW was responsible for the RiverTown Master Development Plan. View project cut sheets for the project:Overview (167 K) and Renderings (615 K). 4,170-Acre Mixed-Use Breaks Ground in Jacksonville By Tonie Auer, Southwest Correspondent After years of waiting to start, officials from the St. Joe Co. and St. Johns County in Jacksonville, Fla., finally broke ground on RiverTown, its 4,170-acre mixed-use project. The two-phase, master-planned community is bounded by Greenbriar Road to the north, County Road 210 to the southeast and the St. Johns River to the west and southwest. RiverTown is just south of Jacksonville and approximately 20 miles from the beaches of Northeast Florida. The land along the east bank of the St. Johns River has been held by St. Joe since 1930 and was historically used for timber production. St. Joe received development approval in February 2004 for the project, which will have 1,125 acres of wetlands, 3.5 miles of riverfront and a 58-acre public park on the St. Johns. Access to RiverTown will be primarily from RiverTown Parkway, which will be extended past Bartram Trail High School, Greenbriar Road and State Road 13. St. Joe plans to begin sales later this year and expects the first closings in 2007. The development will have seven distinct neighborhoods connected to a central square. It will include 4,500 single- and multifamily homes, 100,000 square feet of office space, 300,000 square feet of retail and commercial service space, 100,000 square feet of light industrial space and an 18-hole golf course. St. Joe has proposed a built-out date of 2016 for the RiverTown community. St. Joe worked with design firm Tunnell-Spangler-Walsh & Associates of Atlanta to create the RiverTown Master Development Plan. Town center architects are Looney Ricks Kiss of Memphis; and golf course architect will be Hurdzan-Fry of Columbus. Sales of RiverTown sites are expected to begin in the fourth quarter with a limited number of closings expected before the end of the fiscal year, according to the company’s first quarter 2006 reports. No financial information on the project was disclosed.	cc/2019-30/en_head_0044.json.gz/line3360
__label__wiki	0.906405	0.906405	Romana Town of Regina The Roman past returns through the valuable Roman remains found on the outskirts of the village of Casas de Reina in the province of Badajoz. Roman Town of Regina A highly valuable historical enclave in terms of heritage Casas de Reina , Badajoz (Extremadura) Contact person: Casas de Reina Town Hall Email: turismo@casasdereina.es Email: creina@dip-badajoz.es Website address: www.reginaturdulorum.com Website address: www.casasdereina.com Tuesday to Sunday, except December 25th and January 1st: 10 am-5 pm. Closed on Mondays. Guided visits to the theatre and to the interpretaion centre may be appointed with Casas de Reina Town Hall. Check with Casas de Reina Town Hall. The remains of the Roman town of Regina Turdulorum, found near the municipality of Casas de Reina in Badajoz province, form an extremely interesting ensemble, in a perfect state of preservation, with the forum and a 1st-century-AD theatre as its most remarkable features. The Roman theatre was built in the age of the Flavian emperors, could seat one thousand spectators and was operational until the 4th century AD. The restoration work carried out on the theatre enables one to see the original elements of this space, which was one of the most important of its kind in the Iberian Peninsula. As well as being used for the typical dramatic performances, other activities were also held here. Meanwhile Regina's Roman forum preserves the foundations of some houses, civil buildings, porticoes and the odd remnants of paving or Roman road that transport you directly to this period of history. A porticoed templum with a small room dedicated to the worship of the emperor and the imperial house has also been recovered through different excavations, alongside which other buildings must have existed, such as the market and the basilica. Also noteworthy is the high number of sewers that have been uncovered in the different digs, showing the impressive drainage system of this Roman town, which reached the regional road that links Llerena to Fuente del Arco, where the remains of some Roman villas have also been found. Romanisation (AD) 1st century BC La Jayona Mine Today, these former iron mines have become an ideal refuge for the area's wildlife and vegetation. Colonias de Cernícalo Primilla de Llerena Special Protection Area (SPA) for Birds The area attracts kestrels throughout the year, especially in the breeding season. The Romans founded a city here that you can still visit today, its Regina Roman theatre taking pride of place among the attractions to be seen. The town of Fuente de Arco lies in the south of Extremadura in the foothills of the Sierra Morena mountains. Llerena — an artistic centre The importance of Llerena as a town attracted an endless flow of leading artists who enriched its heritage. Reina Castle Next to the town of Reina, this fortress was built by the Moslems and inherited by the Christians, becoming a part of the Order of Santiago. Chapel of Nuestra Señora del Ara The structure and architecture of the chapel of Nuestra Señora del Ara has evolved over time since it was built in the 14th century, but it still preserves the essence of the Mudejar style. Church of Nuestra Señora de la Granada A religious monument built over an old Mudejar building. This unique building houses a fusion of architectural styles.	cc/2019-30/en_head_0044.json.gz/line3362
__label__wiki	0.836916	0.836916	'Young & the Restless' Showrunner Mal Young Dishes on New Characters & Why Hilary Had to Die Michael Maloney August 31, 2018 11:00 am Q&A Johnny Vy/CBS Earlier this week, The Young and the Restless invited TV Insider to the set of the top-rated CBS soap for interviews over coffee and bagels at Crimson Lights. We took the opportunity to chat up executive producer/head writer Mal Young on some recent developments in Genoa City. Read on to get the scoop! Christel Khalil Downgrades to Recurring Status on 'Young and the Restless' But what will happen to Lane (aka Lily and Cane)? You’re introducing a few family, the Rosales clan, one by one instead of all at once. Mal Young: It can scare people off if you do that. We got to know Arturo (Jason Canela) first. Then, we brought on his brother Rey (Jordi Vilasuso), who’s investigating the case of J.T.’s (Thad Luckinbill) disappearance. They all come in with individual stories, then organically, we bring in [their sister] Lola (Sasha Calle) and you start to see them having family stories. If we did it like, ‘Here’s everybody all at once!’ it would scare everyone off. Will we see their parents at some point? Oh, yeah. There’s a whole story about where the dad is and the mother. Rey has a wife we’re going to be seeing down the line. She’s a big new character for us. We’ve got rich stories for every one of them. Often, it takes a while for a new actor to settle in. Michael Mealor (Kyle) seems to have meshed nicely and quickly with the show’s vets. Yes. He had two mentors when he started — Peter Bergman (Jack) and Jason Thompson (Billy), the two nicest guys in the business. They took him under their wings. Michael has this attitude that he wants to do good work. He passionately cares about it. He doesn’t fear it. He offered to come in on his days off to be part of the casting for Lola. He’s a special human being. He has hit the ground running. Michael Mealor as Kyle (Monty Brinton/CBS) The production values of the show look great; what have you brought to the show in terms of that? Thank you. I hope people recognize that we’ve improved the lighting. We’ve made it more realistic. I’ve tried to make the direction and camera work more cinematic so that it doesn’t feel too ‘soapy’ – if that’s a word. Sometimes you can fall into a very old-fashioned outdated way of shooting drama on multi-camera. Multi-camera has to aspire to look like single camera. The camera moves have to be a particular way. We’ve lost the big zoom-ins. Those old ways are outdated. We’ve moved on from those. You want it to look like a prime time show. Y&R’s lost two big fan favorites this year — Melissa Claire Egan (ex-Chelsea) and Mishael Morgan (ex-Hilary). Can you talk about the decision to write Chelsea out, leaving a return open, while Hilary was killed off? When Missy [Claire Egan, ex-Chelsea] said she wanted to try new things we got the feeling that Chelsea was going off on a little trip and she wasn’t [leaving forever]. Missy and I talked about how this isn’t the end of the story. Chelsea has Adam’s kid. She’s got a big chunk of Y&R history out there. That character will walk back in one day. There’s no doubt about it. Conversely, Hilary went to that big soap in the sky. Why? I haven’t told anyone in the press this story, but I’m going to tell you. When Mishael came to me and said she wanted to move on, we talked about it. She’s a very talented and ambitious actress. She has big dreams. I said to her, ‘You’re not coming back, are you?’ She went no. She said there are so many opportunities for diverse casting now. She was upfront about that. She said I think I’ve got my moment. I said you’ve got the best show reel on TV. You’re leaving at a high. I’ll give you the biggest exit story I can possibly give you. I want you to be the next person we see in prime time. Bryton James (Devon Hamilton) and Mishael Morgan (Hilary Hamilton) (Photo: Cliff Lipson/CBS) What if all those beats had been played — the accident, Devon (Bryton James) and Hilary remarrying, and then Devon walks into the hospital room to find Hilary gone, leaving a note behind that they’d re-wed in haste and she was leaving town to recover? I said to CBS and Sony she’s not coming back. I think we should kill her. Killing her sends out a message to everyone that she’s not coming back. Often soap deaths are never [final] and the viewers see through that. We got a lot of great comments from viewers loving that we did a proper death and showed the proper emotions. We showed the impact on Lily (Christel Khalil), Devon, and Neil (Kristoff St. John). It had repercussions. Also, I didn’t want anyone else playing Hilary. I said to Mishael, ‘You’ve created this amazing, sometimes monstrous, character, I think it would be really hard to recast you and also a disservice to the character if we just went here’s another….actress who’s going to play you now.’ No. She will forever more now be Hilary. That was the best gift we gave her and she was in tears when I told her that. That was the reason we did it, two reasons. Devon will either forgive Lily for Hilary’s death the way the Winters clan appears to have forgiven Phyllis (Gina Tognoni) for her role in Dru’s (Victoria) death – or it’ll be like Phillip (Donnelly Rhodes), where his passing was always there between Kay (Jeanne Cooper) and Jill (Jess Walton). It’s real [for Devon]. His next big story is in trying to come to terms with his sister and his wife. Gina Tognoni (Monty Brinton / CBS) Adam (Justin Hartley) has already “died” once and come back once with plastic surgery. If and when he comes back again, do you write in a second round of plastic surgery to explain a new actor’s face in the role – or do you just not mention it? I try not to think about that because it would keep me awake at night. I don’t know if or when [Adam will be back]. Everyone talks about him a lot. He seems to be a big part of the show. He’s officially dead, but…maybe not? With Nicholas (Joshua Morrow) raising his son, Christian, and becoming more Adam-like, it sets the stage for Adam to return and square off against his brother. There’s nothing to talk about right now [in terms of an Adam return]. 21 Actors to Keep in Mind for Next Year's Daytime Emmys (PHOTOS) The focus might be on the 2018 primetime awards right now, but we already have our picks for 2019's soap set. Nikki (Melody Thomas Scott) killed J.T. (Luckinbill) to save her daughter Victoria (Amelia Heinle) and then they formed a pact with Sharon (Sharon Case) and Phyllis to keep silent. Why? Paul (Doug Davidson), the police chief, and Christine (Lauralee Bell), the district attorney, are sympathetic characters. Why wouldn’t they believe this was self-defense? We picked these four particularly because they naturally don’t get along. Phyllis and Sharon don’t – there’s so much history there. Phyllis doesn’t trust Nikki and Victoria. It’s a fascinating mix. Then you throw into that the cops have always been looking to pin something on the Newmans. Paul and Christine have always wanted that, but they haven’t gotten close enough because of his relationship with Nikki. To bring in an outside [player, namely, Rey] who doesn’t have that history to rock the boat, ask questions, and also be falling over Sharon complicates things nicely. You said you’d like to see an episode of Y&R done with just two actors — Peter Bergman (Jack) and Jess Walton (Jill) or Judith Chapman (Gloria) would be great. Who do you think? (Laughs) I couldn’t answer that. They’re all fantastic. I don’t have pets, regardless of what social media says. But they’re all good enough to do it. That’s why I’m confident that we can do it. We’ve got the actors and the writers to do it! Young and the Restless, weekdays, CBS Catherine Bach to Return as Anita Lawson on 'Young and the Restless'	cc/2019-30/en_head_0044.json.gz/line3364
__label__wiki	0.764871	0.764871	Connecting Communities to Care in Wyandotte County Community health worker Claudia Rodriguez-Rios addresses attendees at a community event Aug. 10, 2016, where the Community Health Council of Wyandotte County, in partnership with Kansas City CARE Clinic, was awarded a $1.9 million grant from United Health Foundation to support its recently launched Community Health Worker Collaborative. As one of seven new community health workers engaged in the local initiative, Claudia spoke of her passion for supporting Wyandotte County residents in accessing the care and resources to address social and health needs. In partnership with United Health Foundation, Community Health Council (CHC) of Wyandotte County is adding seven new full-time community health workers (CHWs) to help improve coordination of local, culturally competent, affordable primary care for lower-income, underserved residents in Wyandotte County. Through the CHC's partnership with United Health Foundation, which provided a $1.9 million grant to help expand the initiative, the additional CHWs will provide more outreach to Wyandotte County residents. CHWs will continue to reduce barriers to care for residents most in need, including diverse populations such as immigrants and refugees, with the goal of reaching more than 10,000 people across Wyandotte County with access to high-quality health care. "I am blessed to have the opportunity to serve my community and witness the impact we have in people's lives," said Carolina Biagi, a CHW serving Wyandotte County's English-, Portuguese- and Spanish-speaking populations. "Our underserved community faces many challenges, so it is beautiful to be there to help families connect with resources and be by their side through the process." Learn more about how we are partnering to build a healthier Kansas. Kansas City, Kan., Mayor Mark Holland addresses attendees at a community event Aug. 10, 2016, where the Community Health Council of Wyandotte County, in partnership with Kansas City CARE Clinic, was awarded a $1.9 million grant from United Health Foundation to support its recently launched Community Health Worker Collaborative. UNITED HEALTH FOUNDATION 21ST CENTURY HEALTH WORK FORCE	cc/2019-30/en_head_0044.json.gz/line3369
__label__wiki	0.846047	0.846047	Home / Defence / Ammunition / Missiles For ATGML 9M133 Kornet Missiles Hartford International Group deliver and supply ammunition and 9M133 Kornet Missiles for ATGML. This missile has a range of 5.5km and is a tandem HEAT warhead type. The Kornet is ranked as one of the deadliest laser guided missiles on the ammunition market, and, due to its impressive range, has a fearsome reputation. The missile weighs in the range of 8.2kg, and at an impressive 152mm, the diameter is one of the largest ATGMLs ever built. The Kornet is deployed by a two-man team and is used as an ATGML for ground forces. A two-man set up involves one person carrying the fire control system as well as the tripod, with the other carries the launch tube loaded with the missile. This can be done with a single user, but it’s far simpler a set-up with two people behind it. One of the pluses for the 9M133 Kornet is that it’s designed to conceal the user, providing cover behind the fire control system and tripod. The Kornet has been reported in the US-led invasion of Iraq in 2003, and then again in 2006, with Israel’s invasion of Southern Lebanon. More recently, this missile has been reported in 2014 in Ukraine. It has a combat record that is impressive, and the Kornet is a missile that has a place in the modern warfare of today. The component of this missile is a fin-stabilised, solid-fuel rocket propellant development. This missile for ATGML sights at 6 rounds per minute, making it one of the most effective ATGMLs around. 9M113 Konkurs Missiles	cc/2019-30/en_head_0044.json.gz/line3370
__label__wiki	0.890516	0.890516	David Allan Coe Mama Lucky Fri, October 11, 2019 General Admission * Standing Room Only * All Ages * Additional $5 Cash Surcharge At The Door For Under 21 * Attendees Under 16 Must Be Accompanied By A Ticketed, Adult Guardian * Posted Times Are Door Times- Events Generally Begin 30-60 Minutes After Doors Open If there's ever been a way to describe DAC, it has got to be his ability to defy categorization. With nearly three decades of following his musical muse wherever it's led, this outlaw has crossed the panorama of American roots music. As well as being a singer, songwriter, guitarist, David is also a magician, deep sea treasure hunter and movie star. His movies include "Stagecoach", "The Last Days of Frank and Jessie James". "Lady Grey", "Buckstone County Prison" and "Take This Job and Shove It" to mention a few. David signed with SUN Records in 1968 and recorded his first album "Penitentiary Blues", all songs that he wrote in prison. In 1973 Columbia Records bought David's contract from Sun and he recorded his first album "The Mysterious Rhinestone Cowboy" several years before Glen Campbell had a hit with the song "Rhinestone Cowboy". Much has been written about David's past and his lifestyle but not much about his achievements over the years. From performing on FARM AID to touring with NEIL YOUNG, KID ROCK and WILLIE NELSON. David's song "Take This Job and Shove It" has received a Million Airplays Certificate from BMI. His "Greatest Hits Album" is PLATINUM and his "First Ten Years Album" is GOLD. He has had sixty-three songs on the Billboard Singles Charts, including "Mona Lisa Lost Her Smile", "The Ride", "Please Come to Boston", "Willie, Waylon and Me", "Jack Daniels If You Please", "You Never Even Call Me By My Name" to name a few. He has written songs for Johnny Paycheck, Tanya Tucker, George Jones, Willie Nelson, Del Reeves, Tammy Wynette, Melba Montgomery, Stoney Edwards, The Oakridge Boys and KID ROCK. Both "Would You Lay with Me" and "Take This Job and Shove It" are million seller songs penned by David. Johnny Cash had recorded David's songs including "Would You Lay with Me" on his current chart topping album entitled "CASH". His tour schedule is never-ending list of SOLD OUT shows. He performs both Country and Rock shows depending on the venue. David also plays in many Casinos’ where he does Las Vegas type shows. David's newest album is on Cleveland International Records. It is called "Songwriter of the Tear" and includes all songs written by David including "The Penny", "Drink Canada Dry", "The Ghost of Hank Williams", "Standing Too close To the Flame", "The Only Thing Missing Is You", "Desperate Man" and others. Perhaps now, David can finally take his place alongside the great stars of Country music, many of whom he influenced. Mama Lucky, aka, Linda Delgado, is a Texas roadhouse blues performer. Originally from Orange, Texas, she was born and raised in southeast Texas, growing up with music inspired by country, blues, gospel, and the Louisiana swamps. Traveling for fifteen years on the road, she has performed with some legends, and for free on street corners. It is all about the music, and the love that goes into it. Though she tried to retire in May of 2018, the music kept calling her back, and she is performing again, giving her gift of music for as long as she can.	cc/2019-30/en_head_0044.json.gz/line3374
__label__wiki	0.62549	0.62549	Virago Writing Tips: A Q&A with Susie Steiner Tags: crime writing, susie steiner, the pool, Virago, writing tips Readers and reviewers have fallen in love with your detective, Manon Bradshaw. What’s your top tip for creating a compelling central character? I think for a character to be real, you mustn’t sugar-coat them. Give them flaws, and I don’t mean adorable romcom flaws, like wearing wacky tights or shopping in flea markets. I mean proper embarrassing/unpleasant aspects to their personalities, because we all have them. Are they riven with envy? Mean-spirited? Tight-fisted with money? Try not to make their flaws ‘likeable’. Go the whole hog. You’ve now written three novels. How do you motivate yourself to start a new novel? Argh, I almost can’t. The beginning is the hardest, because you’re staring at a blank sheet and building from nothing. When I’m in the middle of a novel, I’m really quite motivated, but at the beginning, oh my goodness, I really struggle! I think the only way to think about it, is that something is better than nothing. So write badly: produce some really bad scenes. These can be improved in revision. Blank pages can’t. How do you create great twists – do you plan these from the start or do they occur naturally as you write? I can’t produce ‘twists’ out of thin air. They arise from the complexity of a novel in progress. Also, I think the pressure for a great twist can be too intimidating. Once you start building your edifice, a volt face might present itself, but if it doesn’t, there are brilliant novels out there without the ‘big twist’. What’s one thing you wish you’d known when you were first starting to write? I think it comes down to the character thing – that for a person to be real, they must be ambivalent and chequered. That’s not to say you must write loveless, ghastly people. But I think what freed me up was realising idealised characters are more boring than difficult characters. Is there a writer you think everyone should read? I think if you want to learn about truly nuanced characterisation, take a look at Olive Kitteridge by Elizabeth Strout. I love this novel because Olive is such an impossible person – horrendous in many ways – and yet she is honest and true and you root for her absolutely. Susie Steiner was born in London, studied English at university and trained as a journalist. She worked in newspapers for 20 years, 11 of them on staff at The Guardian. Her first novel, Homecoming, was published by Faber & Faber to critical acclaim in 2013. Her second, Missing, Presumed was a Sunday Times bestseller which introduced detective Manon Bradshaw. It was a Richard & Judy book club pick and was selected as one of the Guardian’s and Wall Street Journal’s books of 2016. Persons Unknown, the sequel to Missing, Presumed, is her third novel. It is published in June and can be pre-ordered here. She lives in London with her husband and two children. Virago and The Pool’s competition to find a New Crime Writer is open to submissions until 21st May. For full details, and to enter, click here. Five Things I’ve Learned About Writing Psychological Thrillers by Clare Mackintosh Agents tell us what they’re looking for in a debut crime submission – The Pool / Virago New Crime Writer award A Q&A with Helen FitzGerald Virago/ The Pool Competition Winner Announcement The top five things I have learned about crime fiction from working in TV – by Claire Evans	cc/2019-30/en_head_0044.json.gz/line3375
__label__cc	0.569786	0.430214	Devops, Tutorials Continuous Integration is not an all-or-nothing affair. In fact, introducing CI into an organization takes you on a path that progresses through several distinct phases. Each of these phases involves incremental improvements to the technical infrastructure as well as, perhaps more importantly, improvements in the practices and culture of the development team itself. In the following paragraphs, I have tried to paint an approximate picture of each phase. Phase 1—No Build Server Initially, the team has no central build server of any kind. Software is built manually on a developer’s machine, though it may use an Ant script or similar to do so. Source code may be stored in a central source code repository, but developers do not necessarily commit their changes on a regular basis. Some time before a release is scheduled, a developer manually integrates the changes, a process which is generally associated with pain and suffering. Phase 2—Nightly Builds In this phase, the team has a build server, and automated builds are scheduled on a regular (typically nightly) basis. This build simply compiles the code, as there are no reliable or repeatable unit tests. Indeed, automated tests, if they are written, are not a mandatory part of the build process, and may well not run correctly at all. However developers now commit their changes regularly, at least at the end of every day. If a developer commits code changes that conflict with another developer’s work, the build server alerts the team via email the following morning. Nevertheless, the team still tends to use the build server for information purposes only—they feel little obligation to fix a broken build immediately, and builds may stay broken on the build server for some time. Phase 3—Nightly Builds and Basic Automated Tests The team is now starting to take Continuous Integration and automated testing more seriously. The build server is configured to kick off a build whenever new code is committed to the version control system, and team members are able to easily see what changes in the source code triggered a particular build, and what issues these changes address. In addition, the build script compiles the application and runs a set of automated unit and/or integration tests. In addition to email, the build server also alerts team members of integration issues using more proactive channels such as Instant Messaging. Broken builds are now generally fixed quickly. Phase 4—Enter the Metrics Automated code quality and code coverage metrics are now run to help evaluate the quality of the code base and (to some extent, at least) the relevance and effectiveness of the tests. The code quality build also automatically generates API documentation for the application. All this helps teams keep the quality of the code base high, alerting team members if good testing practices are slipping. The team has also set up a “build radiator,” a dashboard view of the project status that is displayed on a prominent screen visible to all team members. Phase 5—Getting More Serious About Testing The benefits of Continuous Integration are closely related to solid testing practices. Now, practices like Test-Driven Development are more widely practiced, resulting in a growing confidence in the results of the automated builds. The application is no longer simply compiled and tested, but if the tests pass, it is automatically deployed to an application server for more comprehensive end-to-end tests and performance tests. Phase 6—Automated Acceptance Tests and More Automated Deployment Acceptance-Test Driven Development is practiced, guiding development efforts and providing high-level reporting on the state of the project. These automated tests use Behavior-Driven Development and Acceptance-Test Driven Development tools to act as communication and documentation tools and documentation as much as testing tools, publishing reports on test results in business terms that non-developers can understand. Since these high-level tests are automated at an early stage in the development process, they also provide a clear idea of what features have been implemented, and which remain to be done. The application is automatically deployed into test environments for testing by the QA team either as changes are committed, or on a nightly basis; a version can be deployed (or “promoted”) to UAT and possibly production environments using a manually-triggered build when testers consider it ready. The team is also capable of using the build server to back out a release, rolling back to a previous release, if something goes horribly wrong. Phase 7—Continuous Deployment Confidence in the automated unit, integration and acceptance tests is now such that teams can apply the automated deployment techniques developed in the previous phase to push out new changes directly into production. The progression between levels here is of course somewhat approximate, and may not always match real-world situations. For example, you may well introduce automated web tests before integrating code quality and code coverage reporting. However, it should give a general idea of how implementing a Continuous Integration strategy in a real world organization generally works.	cc/2019-30/en_head_0044.json.gz/line3376
__label__cc	0.56559	0.43441	Things to see and do in the Georgian city of Bath While we were in Britain touring around before the Diamond Jubilee and shooting footage for our upcoming web video series Travels in Britain, we had the chance to visit the stunning Georgian spa town of Bath. It was a lovely visit and it's definitely a place we would like to return to again. Here's a rundown of our favorite stops in Bath! The Roman Baths You can't visit Bath without visiting its Roman Bath ruins. We greatly enjoyed our visit here and it was so much fun to learn about Bath's Roman history. However, expect heavy crowds as this is the most popular tourist attraction in Bath. Definitely take advantage of the audio tour. Give yourself a couple of hours to explore as there is plenty to see and learn about. Bath Abbey Located across the courtyard from The Roman Baths, Bath Abbey is a stunning cathedral that's worth a stop on it's own. It's free and you can walk around, admiring the amazing stonework and beautiful stained glass. Pulteney Boat Tour We really loved taking a Pulteney Boat Tour which takes you on a one hour cruise down the River Avon. You get an interesting perspective of Bath architecture along with helpful commentary along the way. It's a perfect way to end a day in Bath. Sally Lunn's Sally Lunn's is most famous for its sweet buns but the restaurant itself is now a popular tourist attraction due to its gourmet menu of hearty English food. Its best to make a reservation or get there early to snag a table before the tourists do! Bizarre Bath Walking Tour This walking tour is a lot of fun. It has nothing to do with history but you're taken on an amusing trek through central Bath by a comedian who will have you laughing hysterically. There's a lot of walking and quite a few stairs, but its definitely worth it! Bring a sweater even if its summer as it cools down quickly at night in Bath! Royal Victoria Park While its a bit of a walk from the City Centre, Royal Victoria Park is a great stop for families as they're children's park is world class. There's plenty to see and do and admire in this amazing free public park. Royal Crescent Not far from Royal Victoria Park is the famous Royal Crescent row of houses. You have to stop and take a few pictures and if you want to go a little more in depth, stop at No. 1 Royal Crescent which is a restored Georgain Villa as it would have been when the street was built. You get a lovely little insight into Georgain life. Parade Gardens If you looking for a nice way to end the day, stop at a grocery store and buy some food for a picnic then head down to the Parade Gardens. You have to pay a little bit of money to get into this park, but its located next to the River Avon with prime views of Bath. There's plenty of day chairs to relax, enjoy a cup of tea and if you're there on a weekend, there will most likely be a band performing in the bandstand. What's your favorite attraction in Bath? Let us know in the comments below! This post was brought to you by Anglotopia.net, the website for people who love Britain. Let's go to Edinburgh's Festivals! 48 hours in...Liverpool Five family-friendly activities in London fit for Royalty	cc/2019-30/en_head_0044.json.gz/line3377
__label__wiki	0.973775	0.973775	Post Nation Michael updates: At least 6 killed by storm in Florida, Georgia and North Carolina By Mark Berman , Mark Berman National news reporter Antonia Noori Farzan , Antonia Noori Farzan Reporter for the Morning Mix Eli Rosenberg and Eli Rosenberg General assignment reporter covering national and breaking news J. Freedom du Lac National, international and breaking news Tropical Storm Michael continues to march through the Southeast, still packing powerful winds and flood-causing rains. Michael made landfall in the Florida Panhandle on Wednesday as a “potentially catastrophic” Category 4 hurricane — the strongest on record to hit the area — and charged north through Georgia and into the Carolinas and Virginia, wreaking havoc and causing emergencies. In the storm’s wake lay crushed and flooded buildings, shattered lives and at least six deaths, a number that officials worry could rise. See the latest from the Capital Weather Gang here and track the storm’s path here. 8:25 p.m.: Rivers rise after storm hits North Carolina The storm passed through the Chapel Hill N.C. area on Thursday, but the rain and wind weren’t the end of it. At dusk in Bynum, small former mill town on the Haw River, residents made their way down to the old one-lane road over the river. Waters are still rising along the Haw, which is forecast to reach major flood stage at Bynum early Friday morning. John Pardue, 42, who strolled down to the bridge with his two children, Felix, 9, and Eliza, 12, said the severity of the storm took him by surprise. After the power went out at his guitar shop in Carrboro, he headed home just after one of several powerful squalls blew through the area. “Where I was at in Carrboro it wasn’t that bad, but when I got on the road there was debris everywhere and the power was out,” he said. On the bridge, with rain just misting and an eerie, filtered sunset lighting waters crashing through the rocky riverbed below, Pardue said he’s seen the Haw this high just a few times. Yet the river had yet to reach levels he saw just last month. “A few weeks ago when Florence came by it was much higher than this. You couldn’t see any of those rocks,” he said. “I’m not not worried, because where my place is it’s not a problem, but I’m sure people who live closer down here must be worried.” — Kirk Ross 7:59 p.m.: Storm’s remnants move through Central Virginia As Hurricane Michael travels north, the effects of the rain and wind pushed into Virginia, leaving flooding and power outages in cities along the North Carolina border and in the Central part of the state. Nearly 145,000 Virginians were without power as of 7:11 Thursday evening, according to the Virginia Department of Emergency Management, which advised those with power to charge mobile devices and locate flashlights. The National Weather Service in Blacksburg and near Farmville each reported “extremely dangerous” flooding situations, including water rescues and flash flood warnings. EXTREMELY DANGEROUS CONDITIONS in Farmville, VA. Numerous homes, businesses, and roads are flooded. Please do not venture out this evening! A Flash Flood EMERGENCY remains in effect. #vawx https://t.co/GN1APzM62i — NWS Wakefield (@NWSWakefieldVA) October 11, 2018 A tornado watch was also declared for Hanover County, just north of Richmond. Meantime, according to the Associated Press, Roanoke, Blacksburg and Danville each reported street flooding on Thursday afternoon. Police in Danville said on Twitter that flooding has closed streets throughout the city along the North Carolina border. The police department said rescuers were trying reach motorists and other people trapped by the flooding. The Capital Weather Gang reports that up to seven inches of rain is expected to fall in a short time. Although the Washington area is not under a flood watch, parts of the Southeast suburbs as far as the Delmarva peninsula are. — Keith McMillan 4:47 p.m.: At least 6 deaths in Florida, Georgia and North Carolina linked to storm, officials say Authorities said Thursday they have linked at least six deaths in Florida, Georgia and North Carolina to the storm, a toll officials have worried could rise as search-and-rescue efforts continue. In Florida, the Gadsden County Sheriff’s Office reported four deaths related to the storm. A spokeswoman said that one man was killed when a tree crashed through the roof of his home in Greensboro. The sheriff’s office said that it also had three other “storm-related fatalities following Hurricane Michael,” although it did not immediately release further information about what happened beyond saying that all four deaths were “in relation to or occurred during the storm.” Gadsden, a county in northwest Florida not far from Tallahassee, took a direct shot from Michael as it churned northward on Wednesday. In North Carolina, a 38-year-old man was killed Thursday afternoon shortly before 1 p.m. in Iredell County, north of Charlotte, when a tree fell on the vehicle he was driving, according to David Souther, the county’s fire marshal. And in Georgia, officials in Seminole County, on the Florida border, said early Thursday that an 11-year-old girl in a mobile home was killed by a metal carport that was thrown in the air by Michael’s gusting winds. William “Brock” Long, the FEMA administrator, said early Thursday that “search and rescue is where we are hyper-focused this morning.” He warned that the death toll may go up, saying in an appearance on CNN that “those numbers could climb as search-and-rescue teams get out.” — Mark Berman 2:55 p.m.: Virginia governor declares emergency Virginia Gov. Ralph Northam (D) on Thursday declared a state of emergency in advance of the storm’s impact, warning people in the commonwealth to get ready for a sizable hit from the former hurricane. “I want to urge all Virginians to prepare for the serious possibility of flash floods, tropical-storm-force winds, tornadoes and power outages,” Northam said in a statement. In his executive order, Northam said he was activating the state’s emergency operations center as well as the Virginia National Guard. Northam’s announcement comes after officials in the five states already hit by Michael — Florida, Georgia, Alabama, South Carolina and North Carolina — all declared emergencies. Much of Virginia was under tornado watches and flash flood watches Thursday, with rainfall of up to seven inches predicted in some parts of the state, a total that could lead to dangerous flooding. 1:45 p.m.: Tyndall Air Force Base takes “widespread” damage Hurricane Michael pummeled Tyndall Air Force Base, near Panama City, Fla., causing “widespread roof damage to nearly every home and leaving the base closed until further notice, officials said. Tyndall is located just east of Panama City, which endured punishing winds and took intense rain from the storm. “At this point, Tyndall residents and evacuated personnel should remain at their safe location,” said Col. Brian Laidlaw, 325th Fighter Wing commander. “We are actively developing plans to reunite families and plan to provide safe passage back to base housing.” In a statement, officials said the that the “catastrophic” storm delivered a direct hit to the base, “bringing down trees and power lines, ripping roofs off buildings and causing significant structural damage.” Michael’s winds topped 150 miles per hour. No injuries have so far been reported, the base said, but the condition of Tyndall’s runway is not yet known. Tyndall’s mandatory evacuation order was declared Monday, and it remains in effect. The 600 families who live on base were offered space in local shelters. “Initial assessments of the damage at Tyndall Air Force base have identified severe damage to the base infrastructure,” according to an Air Force official. “There is no power, water or sewer service to the base at this time. All personnel assigned to ride out the storm are accounted for with no injuries. The Air Force is working to conduct aerial surveillance of the damage, to clear a route to the base and to provide security, potable water, latrines and communication equipment. The base will remain closed and Airmen assigned to Tyndall should not plan to return at this time.” — Emily Wax-Thibodeaux Tyndall Air Force Base suffered extreme damage from Hurricane #Michael as it came ashore. Nearly every structure on base suffered roofing damage according to the base commander. #flwx #tropics pic.twitter.com/9WeXTwMSu4 — Zach Covey (@ZachWPDE) October 11, 2018 1:10 p.m.: Trump declares disasters in Georgia, Florida President Trump approved disaster requests for Georgia and Florida stemming from the hurricane, moves that authorize federal authorities to coordinate response efforts while also opening up federal funding to officials in those areas. The White House said Trump declared a major disaster in Florida, while FEMA said that he had signed an emergency declaration for Georgia. In remarks Thursday, Trump addressed the hurricane, noting that it had swept through the area quickly. “The big problem with this hurricane was the tremendous power, and fortunately it was very fast,” he said Thursday. “It went through Florida very, very quickly.” Trump also defended his decision to hold a political rally in Pennsylvania on Wednesday night, an event that occurred while the storm, then still packing hurricane-force winds, was still churning through the Southeast, saying that he could not disappoint the people already in line. — Mark Berman and Felicia Sonmez [Democrats attack Trump for campaigning while deadly hurricane slams Florida] 12:30 p.m.: What’s next for Tropical Storm Michael The storm once known as Hurricane Michael has weakened, but it continued to batter the Southeast on Thursday, and the impact will continue to spread in the coming day. Forecasts now call for Michael to sweep across the Carolinas and then southeast Virginia through the day, dropping up to seven inches of rain in some areas, which could lead to flash flooding. Other areas could see up to three inches of rain, but more than twice that amount could fall in a swath from Charlotte to Richmond and on to Salisbury, Md. Head to the Capital Weather Gang for the latest on where the storm is going now. 11:52 a.m.: Cajun Navy charges into Florida Just as they did last summer in Texas during Hurricane Harvey and last month during Hurricane Florence, several groups of grass-roots, ragtag search-and-rescue teams have arrived in Michael’s wake. But this time, even the experienced Cajun storm chasers say they are more cautious due to the number of downed trees and telephone poles. “This one just looks like a bomb dropped,” said Clyde Cain, a self-described admiral with the Louisiana Cajun Navy. “This one is so powerful that my guys are having to use chain saws to cut through downed trees to get into the neighborhoods. This one is just real bad, and no one saw it coming. We were just recovering from Florence.” Cain, who was at a command center they set up in Mobile, Ala., said he’s been so busy after Hurricane Florence that “my mama still hasn’t seen me.” He said he was warning his guys this time to be even more careful, “there are a whole lot of telephone poles dropping. This one is just real dangerous.” 10:50 a.m.: North Carolina, reeling from Florence and now lashed by Michael, “adds unwelcome insult to injury” As the remnants of Hurricane Michael began to spread across North Carolina, state officials warned on Thursday morning that residents were feeling an impact that would only worsen. Tens of thousands had lost power, at least 16 roads were closed, dozens of school systems shuttered and three rivers were poised for moderate or major flooding, authorities said. Gov. Roy Cooper (D) offered his thoughts for the other states that bore the brunt of the storm, something that North Carolina is grimly familiar with after Hurricane Florence delivered deadly flooding last month. “People in North Carolina know all too well what that feels like,” he said to his neighbors to the south. “For North Carolina, Michael isn’t as bad as Florence, but it adds unwelcome insult to injury, so we must be on alert.” The National Hurricane Center said that shortly before 11 a.m., the center of Michael was about 35 miles away from Charlotte and “producing heavy rainfall and tropical-storm-force wind gusts” across much of the central and eastern parts of both Carolinas. Tropical-storm-force winds extend up to 185 miles from the storm’s center, mostly to the south and east, with a wind gust of 54 mph reported in South Carolina. “On the forecast track, the center of Michael will continue to move across central and eastern North Carolina today, move across southeastern Virginia this evening, and move into the western Atlantic Ocean tonight,” the hurricane center said. 10:20 a.m.: FEMA: “Mexico Beach took the brunt” FEMA chief William “Brock” Long said that Mexico Beach, Fla., not far from where Hurricane Michael made landfall as a powerful system, appeared to be “Ground Zero” of the storm’s impact. “Mexico Beach took the brunt,” Long said during a news briefing Thursday morning in Washington. “That’s probably Ground Zero.” Still, Long noted that authorities still had not “been able to get in and truly assess” the damage, which he said would take some time over the next two days. Long warned people in the region to expect a long-lasting impact from the storm, which spent much of Wednesday battering Florida before it thundered north across Georgia and South Carolina. He pointed in particular to the power outages affecting hundreds of thousands of people across Florida, Georgia, Alabama and the Carolinas, saying that it could take weeks for the lights to come back on everywhere because of the damage. “It’s not just power lines being down, it’s transformers that are down, it’s substations that have been impacted,” Long said. “This is not stuff that you just put back together overnight.” There was a sliver of good news, Long said: Officials were not expecting additional flooding in the parts of the Carolinas that suffered flooding during Hurricane Florence. But some parts of the coastal Carolinas were facing a threat of storm surge, he said, warning people in the area: “It’s not over.” 10:05 a.m.: Florida governor: “We will recover and we will do it together” Gov. Rick Scott (R) on Thursday morning urged Floridians to remain cautious even as the remnants of Hurricane Michael have moved north, saying that the storm’s aftermath could pose a threat to people in the Florida Panhandle region. Scott said he remains concerned about people who did not evacuate during the storm. As of Thursday morning, he said the state has only confirmed one fatality due to the storm; Georgia has also reported one death from the storm. “Hopefully everybody made it through the storm,” Scott said. “Be safe. There’s downed power lines, don’t touch them. There’s a lot of trees down, don’t get injured. If you’re going to use a generator, make sure you know how to use it properly.” He added: “We will recover and we will do it together.” Scott noted that the storm came on quickly and left just as rapidly after tearing through Florida for much of Wednesday. “I know this thing came up fast,” he said. Still, he pleaded again with people who evacuated coastal communities not to return yet, saying: “Everyone needs to stay off the roads.” 9:20 a.m. update: More than 750,000 power outages reported across Southeast The storm has knocked out power to more than 754,000 across the Southeastern United States, with more than half of those outages occurring in Florida, where Michael first made landfall Wednesday as a powerful system. Florida officials reported about 400,000 outages as of Thursday morning, with power entirely or largely knocked out in counties including Bay, Gulf and Jackson. In Georgia, more than 174,000 customers lacked power on Thursday morning. South Carolina had about 114,000 outages, while North Carolina (more than 23,000 outages) and Alabama (about 43,000 outages) both had wide swaths of people without power. 8:44 a.m.: Michael moves over South Carolina and heads for North Carolina After wreaking havoc across the Florida Panhandle and Georgia, the storm’s center was moving over South Carolina on Thursday morning, its tropical-storm-force winds extending out across that state and Georgia, according to the National Hurricane Center. The storm was about 40 miles west of Columbia, S.C., at 8 a.m., and tropical storm warnings extended from Georgia through the Carolinas. The strongest winds were mostly spreading north along the coastlines of the Carolinas, with maximum sustained winds near 50 mph, the center said. The hurricane center said Michael would keep moving quickly toward the northeast. On its current track, the storm is forecast to move through the center of South Carolina on Thursday morning, then rumble across parts of central and eastern North Carolina before shifting across southeastern Virginia in the afternoon or evening. Forecasters say Michael is expected to move out into the Atlantic Ocean by late Thursday or early Friday. 8:17 a.m.: Florida Gov. Rick Scott: ‘Stay safe’ Before heading to the Gulf Coast to survey the damage, Gov. Rick Scott (R) had a message for Floridians: “You survived this unbelievable storm; stay safe.” There are downed power lines and downed trees “all over the place,” Scott said on CNN, noting that there was “unbelievable devastation.” “Stay in your house, listen to the locals, be safe — don’t do anything foolish,” said Scott. Two Michael-related deaths have been confirmed, including one in Florida, and the governor noted that “we have a lot of people I’ve heard are injured.” He added: “My biggest concern would be loss of life.” — J. Freedom du Lac 7:55 a.m.: Mexico Beach ‘wiped out’ FEMA Administrator William “Brock” Long said early Thursday that “search and rescue is where we are hyper-focused this morning” — particularly in Mexico Beach, Fla., which “was wiped out” by Hurricane Michael’s storm surge, he said. “We have a lot of work to do … there’s a lot of debris that we’ve got to get through,” Long said on CNN. “We’re trying to get into areas like Mexico Beach, get the teams in to be able to assess damage.” Long was asked about Michael’s confirmed death toll, which stands at two. “Those numbers could climb,” he said. “Hopefully they don’t, but those numbers could climb as search-and-rescue teams get out.” Another priority, Long said: Restoring the power throughout the Southeast. “You fix the power, you solve a lot of problems,” he told Fox News. More than half a million people across Florida, Georgia and South Carolina have lost power due to the storm. It may be weeks before some of them get their electricity back, Long said. 6:47 a.m.: ‘Absolutely catastrophic!’ The sun will rise across the Florida Panhandle sometime around 7 on Thursday, and Hurricane Michael’s trail of destruction will begin to come into clearer focus. But the early indicators are troubling. Consider what storm chaser Josh Morgerman tweeted Wednesday night: “It’s hard to convey in words the scale of the catastrophe in Panama City. The whole city looks like a nuke was dropped on it. I’m literally shocked at the scale of the destruction.” Morgerman has chased some of the most extreme hurricanes and typhoons across the world. As the Capital Weather Gang noted, “he is not prone to hyperbole.” Early Thursday, he said that Michael was “definitely one of the most violent [hurricanes] I’ve been in.” Another storm chaser, Mark Sudduth, tweeted: “Drove from Panama City almost to Mexico Beach and I can tell you this is the worst damage from wind that I have ever seen! Absolutely catastrophic! You will not believe your eyes when you see it.” Sudduth added: “Walking thru Mexico Beach to receive my GoPro cam and I’m telling you, it’s DEVASTATED. Truly devastated. Some buildings completely swept clean — only slabs.” 5 a.m.: Michael continues to weaken as the storm heads toward the Carolinas. Tropical Storm Michael keeps getting weaker as it crosses rain-soaked Georgia and moves northeast toward South Carolina, the National Hurricane Center said in its latest update. By 2 a.m., sustained winds had decreased to 60 mph; at 5 a.m., they had fallen to 50 mph. However, the center said, winds have picked up at certain points along the Georgia and South Carolina coast. Large parts of Georgia, the Carolinas and southeastern Virginia could still see deadly flash floods today and remain under a tropical storm warning. The storm’s center is currently about 30 miles west of Augusta, Ga., near the South Carolina border. Forecasters expect that Michael will continue to weaken today as the storm travels over land, likely reaching central South Carolina this morning. Once Michael reaches the Atlantic, the storm is expected to intensify again as it becomes a post-tropical low. — Antonia Farzan [People are freaking out over this ‘creepy skull’ spotted in Hurricane Michael’s satellite imagery] 3:30 a.m.: Apple CEO, a Gulf Coast native, pledges to help with recovery. On Wednesday night, Apple CEO Tim Cook pledged that the company would help with recovery and relief efforts. “I grew up on the shores of the Gulf Coast, near Pensacola and Mobile, and that region holds a special place in my heart,” he wrote on Twitter. “That’s never been more true than now.” Cook grew up in Robertsdale, Ala., a city of roughly 5,200 people located roughly halfway between Mobile and Pensacola, Fla. His father worked at Mobile’s shipyards, and his mother worked at a drugstore. Though Cook has called himself a “a proud son of the South,” his relationship with the socially conservative community where he grew up is complicated. When Cook came out as gay in 2014, Robertsdale Mayor Charles Murphy suggested that he should have kept his sexual orientation private. “Tim has done a good job with Apple. We’re very proud of the accomplishments that he’s made,” he told Reuters. “Sometimes people’s personal lives need to stay personal.” Visiting Robertsdale in 2016, The Washington Post’s Todd Frankel noted that Cook’s name wasn’t on the town’s welcome signs, the chamber of commerce brochures, or at his old high school. One former classmate speculated that the lack of recognition might be connected to Cook’s advocacy for gay rights. Apple is standing with our friends and neighbors in the Gulf Coast region, and will be donating to recovery and relief efforts. — Tim Cook (@tim_cook) October 11, 2018 2 a.m.: Officials in Georgia’s Seminole County confirm a second storm-related fatality. High winds from Hurricane Michael lead to the death of an 11-year-old girl in Seminole County, Ga., EMA Director Travis Brooks told The Washington Post early Thursday morning. The girl had been inside a trailer home in an unincorporated area of the county near Lake Seminole, close to the Florida-Georgia border. From what officials could determine, Brooks said, it looked like a metal carport used to store boats had been lifted in the air by the gusting winds and had flipped over. When it landed, its legs crashed through the roof of a neighboring mobile home and hit the girl in the head. “It looked like a war zone,” Brooks said, adding that it had taken deputies from the Seminole County Sheriff’s Office practically all day to get to the mobile home due to the road conditions in the area. The death is the second known fatality connected with Hurricane Michael, which has since been downgraded to a tropical storm. 1:30 a.m.: Michael weakens to a tropical storm over South-Central Georgia. After crushing the Florida coast, Hurricane Michael weakened as it passed through south-central Georgia on Wednesday night. By midnight, peak winds had dropped to 70 mph, causing forecasters to reclassify it as a tropical storm. Heavy rainfall is expected to continue drenching Georgia through the early hours of the morning, with a threat of flash flooding overnight. Meanwhile, the Waffle House near Florida State University’s campus in Tallahassee was open for business at 12:28 a.m., with lines stretching out the door. FEMA officials famously use the Waffle House Index as a way of measuring storm damage: Since the diner chain is ubiquitous in the southeast, and rarely shuts down in extreme weather, seeing the Waffle House closed down before a storm is a sign that things are about to get extremely bad. If the Waffle House hasn’t reopened after the storm, FEMA considers that a sign that the area has experienced major devastation. There’s one place open in Tallahassee tonight ->@spann @NWSTallahassee @abc3340 #HurricaneMichael #alwx pic.twitter.com/F0XjYNdZPK — Stephen Quinn (@StephenQ3340) October 11, 2018 On Wednesday morning, a Waffle House spokesman had announced that 30 restaurants in Florida and Georgia were closed in preparation for Hurricane Michael, including locations along the Florida Panhandle from Panama City to Destin. It was a clear warning that the storm should be taken seriously. 10:35 p.m.: Stunning visuals from Florida Before the sun went down and the skies turned midnight blue, those in the path of Hurricane Michael shared glimpses of what some say is the worst hurricane damage they’ve seen. “We’re kind of getting crushed,” Franklin County Sheriff A.J. Smith said to The Washington Post. “It’s horrific.” Here are three photos that capture the awe such a powerful storm brings. A car is seen caught in floodwaters in Panama City, Fla. (Jabin Botsford/The Washington Post) Jason Phipps looks through his family’s roofless apartment after Hurricane Michael made landfall in Panama City, Fla. (Jabin Botsford/The Washington Post) Unedited sunset in Apalachicola FL pic.twitter.com/nIRlu19qYb — Mike Bettes (@mikebettes) October 10, 2018 10:05 p.m. Storm chasers say they are shocked by the damage Images of the destruction in coastal Florida towns circulated widely Wednesday night, shocking even seasoned storm chasers and weather watchers. Smith, the sheriff of Franklin County, a coastal patch south of Tallahassee, told CNN that the county was nearly isolated after most of the main roads were rendered impassable from flooding and downed trees. “It’s bad,” he said. “We’ve been through hurricanes but never where we were completely cut off like this.” Linda Albrecht, a councilwoman in Mexico Beach, spoke to the network about leaving her home with only a few essential objects. “It feels like a nightmare,” she said. “Looking at the pictures, I’m thinking there is not a house left in that town.” Downtown Panama City proper got hit way harder than Panama City Beach. Not shocked as it was hit by the right eyewall. This is catastrophic damage here. @weathernetwork @StormhunterTWN #HurricaneMichael pic.twitter.com/Y7rUyHE7Wj — Jaclyn Whittal (@jwhittalTWN) October 10, 2018 — Eli Rosenberg 8:16 p.m.: Local TV station is knocked off the air, but continues reporting The storm knocked the broadcast of Panama City-based WMBB off the air after the television station lost power, one of more than 263,000 customers experiencing blackouts in Florida. But that didn’t stop the journalists from getting the report out. Reporter Peyton LoCicero went on Periscope, an app that allows people to live stream to a public audience from a cellphone, to give updates about the storm. She spoke from the parking lot of a wrecked gas station in Walton County, tilting the camera to show the damage around her. The station’s awning had crashed to the ground. “I wanted to let you guys know exactly what is going on,” she said, speaking about a curfew that had been instituted in nearby Bay County because of concerns about looting from the outages. More than 17,000 people tuned into the broadcast, including Sen. Marco Rubio, who shared LoCicero’s impromptu report on Twitter. .@WMBBTV has been knocked off the air. But reporter @PeytonLocicero is doing live reports from the scene covering #HurricaneMichael on periscope. Sign up to be notified when she goes live. #Sayfie https://t.co/1AZtvhbUxl — Marco Rubio (@marcorubio) October 10, 2018 7:55 p.m.: First confirmed fatality of the storm The Gadsden County Sheriff’s office said that a man was found dead in his home in a small town outside of Tallahassee after a tree crashed through the roof. Sgt. Angela Hightower did not identify the man but said he had been found at the home in Greensboro around 6 p.m. 7:01 p.m.: The storm begins moving through Georgia, sending tornado warnings through at least three counties The eye of Hurricane Michael began to move through southwest Georgia on Wednesday evening — the first major hurricane to reach the state since the 19th century, according to local reports. Winds gusts of around 60 mph were reported in towns near the Georgia-Alabama border, according to the National Weather Service. A dangerous storm surge continued along the coastal Florida panhandle; a National Ocean Service station in Apalachicola was reporting 5 feet of water above the ground level. And tornado warnings radiated out into counties near the hurricane’s path in Georgia on Tuesday evening, after reports of at least two that had formed in Florida. Officials issued brief tornado warnings for Fulton, Douglas and Cobb counties. More than 40,000 people lost power across the state. #HurricaneMichael was captured from the space station today after the storm made landfall as a category 4 hurricane over the Florida panhandle. The @NHC_Atlantic reported maximum sustained winds near 145mph. https://t.co/e7BKY7Qbx5 pic.twitter.com/6tvMhLJ2Yr — Intl. Space Station (@Space_Station) October 10, 2018 Mark Berman Mark Berman covers national news for The Washington Post. He has been at The Post since 2007 and previously covered transportation and local news. Follow Antonia Noori Farzan Antonia Noori Farzan is a reporter on The Washington Post's Morning Mix team. She previously worked at the Phoenix New Times. Follow Eli Rosenberg Eli Rosenberg is a reporter on The Washington Post's General Assignment team. He has worked at the New York Times and the New York Daily News. Follow J. Freedom du Lac J. Freedom du Lac is editor of The Washington Post's Live News desk. He previously served as General Assignment news editor and, before that, was a news features writer and The Post's pop music critic. Follow Leaf Page Test - Wed Jul 17 16:36:01 EDT 2019 Nancy Pelosi was rebuked for calling Trump’s tweets racist. She can thank Thomas Jefferson and the Brits. A white IRS security guard pulled a gun on an armed man. It was a black police officer — in uniform. Opinion Can you guess which GOP lawmaker gets the booby prize for moral imbecility? Opinion Marianne Williamson is the only true anti-Trump	cc/2019-30/en_head_0044.json.gz/line3378
__label__wiki	0.944895	0.944895	Trump administration to start sending asylum seekers to wait in Mexico Migrants are escorted by a U.S. Border Patrol agent after they were detained at San Ysidro, Calif., in December. (Rebecca Blackwell/AP) By Andrew deGrandpre , Andrew deGrandpre Deputy national security editor Maria Sacchetti , Maria Sacchetti Reporter covering immigrant communities and Immigration and Customs Enforcement Kevin Sieff and Kevin Sieff Latin America Correspondent David Nakamura Reporter covering the White House U.S. officials at the southern border will begin sending some asylum applicants back to Mexico on Friday as the Trump administration implements new measures preventing migrants from waiting in the United States while their cases are processed. The initiative, announced by the Department of Homeland Security on Thursday night, follows high-level talks between the two governments late last year as U.S. border officials struggled to contend with waves of Central American migrants fleeing violence and poverty. It will be introduced in California, at the San Ysidro port of entry south of San Diego, and eventually expanded throughout the nearly 2,000-mile border, a DHS official said earlier Thursday, speaking on the condition of anonymity because the plan had not yet been finalized. [Deal with Mexico paves way for asylum overhaul at U.S. border] The Trump administration has struggled to devise effective deterrents, and its other attempts — including the forced separation of migrant children from their families — have incited enormous public backlash. This latest effort comes as parts of the federal government are shut down over the president’s demand for border wall funding and Democrats’ refusal to provide it. According to a fact sheet distributed by DHS, these new measures will apply to “certain aliens attempting to enter the U.S. illegally or without documentation, including those who claim asylum.” It says they will no longer be released into the country, “where they often fail to file an asylum application or disappear before an immigration judge can determine the merits of any claim to prevent removal.” In an accompanying statement, Homeland Security Secretary Kirstjen Nielsen called the new measure “unprecedented” and intended to address “the ongoing humanitarian and security crisis at our Southern border.” “For far too long,” Nielsen said, “our immigration system has been exploited by smugglers, traffickers, and those who have no legal right to remain in the United States.” The plan had been informally called Remain in Mexico and followed delicate negotiations with the administration of Mexico’s new leftist president, Andrés Manuel López Obrador, who took office Dec. 1. On Thursday, officials referred to the initiative as the Migrant Protection Protocols, saying both countries are simply implementing their own laws. Homeland Security officials have described the plan as one of the most significant changes to immigration policy in decades. Immigrant rights groups have opposed it, saying it violates U.S. and international asylum laws and could face court challenges. “The president thinks he can do this unilaterally,” said Kevin Appleby, a senior director at the Center for Migration Studies. “But it’s a blatant rejection of current law.” White House officials did not respond to requests for comment Thursday. Tonatiuh Guillén, who heads Mexico’s immigration agency, said he had not received any communication from the United States about when implementation of the measures would begin. “Part of the difficulty is that we have very few explicit definitions, and a very noisy environment, with many rumors, and we have not managed to refine what [the plan] entails,” he said Thursday afternoon. Guillén said he was concerned about the measures and Mexico’s ability to accommodate migrants who could spend months or years in the country as their asylum claims are processed. His first concern, he said, was the humanitarian situation. “We don’t have the capacity” to absorb many migrants beyond their initial reception, he said. “It is a challenge of living conditions, of public services,” he added, saying that it was unclear to Mexico’s immigration agency whether the U.S. government planned to keep only a fraction of its asylum seekers in Mexico, or the many thousands who apply each year. “If it is a very small scale, it would not be significant,” Guillén said. “If it is a higher-level scale, we would be in some difficulty, which would force a change in the way Mexico conducts its reception” of migrants. DHS said late Thursday that the United States had notified Mexico “that it is implementing these procedures under U.S. law,” and the official said the department intends to start gradually. In its statement, Homeland Security contends that the Immigration and Nationality Act authorizes it to carry out the action. Starting Friday, migrants who arrive at San Ysidro will be told they must go back across the border — even if they are not Mexican citizens — while U.S. immigration officials assess their claims, DHS officials said. They will receive a notice to appear in court and a toll-free number to call for status updates. “Aliens who need to return to the U.S. to attend their immigration court hearings will be allowed to enter the U.S. and attend that hearing,” the DHS fact sheet says. “Aliens whose claims are found meritorious by an immigration judge will be allowed to remain in the U.S. Those determined to be without valid claims will be removed from the U.S. to their country of nationality or citizenship.” The new approach represents a significant departure from long-standing asylum-screening procedures and comes as the administration struggles to handle a record surge of Central American families coming to the southern border. In fiscal 2018, 107,000 migrant family members were taken into custody by U.S. border security officials, surpassing a record set in 2016. Trump administration officials have acknowledged that the president’s proposed border wall would have little effect in stemming the flow of migrant families seeking asylum, as they often surrender to authorities, in accordance with the law, once they arrive on U.S. soil. Currently, migrants requesting asylum can avoid immediate deportation by establishing that their lives would be endangered if they were returned to their home countries. Immigration courts are backlogged with hundreds of thousands of asylum cases, so migrants are released into the United States to await their hearings — a process that can take more than a year. Trump and other immigration hard-liners detest this system, calling it “catch and release.” Under the new measures, if asylum seekers do not fear persecution in Mexico, then they must stay there while their cases are processed. To implement the new procedures, U.S. Citizenship and Immigration Services was expected to dispatch additional asylum officers to San Diego from the agency’s field offices in California and Washington, D.C. San Ysidro continues to be a destination for migrants traveling as part of large caravan groups that originate in Central America, a trend that has become exceedingly frustrating for Trump. The port has experienced disruptions in recent months as migrants forced to wait in Tijuana have grown impatient and rushed the border. The new initiative is one of several hard-line measures the administration has sought to implement at the border, including the deployment of several thousand military personnel and the separation of thousands of migrant children from their families — a policy Trump eventually reversed after widespread condemnation. The administration’s attempt to ban Central Americans from seeking asylum was blocked in federal courts last fall. Over the weekend, Trump offered Democrats a deal to end the partial government shutdown that included a provision to force Central American minors to remain in their own countries while seeking asylum in the United States. That plan was fiercely opposed by Democrats and immigrant rights groups. A Republican bill including that provision was soundly defeated in a Senate vote Thursday. Sieff reported from El Salvador.	cc/2019-30/en_head_0044.json.gz/line3379
__label__cc	0.667887	0.332113	Emporio Armani is a brand known for its high-quality luxury products. Innovation and following the latest trends is at the heart of the brand. Its products are available in boutiques all over the world. Emporio Armani is the only line of the Armani Fashion house which is designed by its founder. Minimalist sports elements and casual cuts are visible in the brand’s collections and show Giorgio's consistency in creating luxurious, simple clothing and accessories. Please choose a collection from this designer: New items in the category: MEN Logo-embroidered scarf Tuxedo shirt Quilted down jacket New items in the category: WOMEN Branded wash bag Logo-embroidered jacket Branded jeans Logo-patched jeans Emporio Armani - luxury in minimalism, minimalism in luxury Born in Italy on July 11, 1934, Giorgio Armani already loved and understood fashion in his youth. However, he did not have any direct contact with fashion in his early days. The course of education which he undertook concerned areas that were very distant from it. He started medical studies after high school but did not end up graduating. He interrupted his education after two years of study to start photography. After returning from military service, he started working at the famous La Rinascente department store in Milan, arranging the decor of store windows and was quickly promoted. After the proposal of the Nino Cerruti brand, he changed jobs and worked as a male line designer in the new company. The birth of a superpower Supported by his partner, Sergio Galeotti, he founded a design studio in 1970. While realizing orders for other companies, he came to the conviction that he should create his own brand. In July 1974, he and his partner established a new brand that was named after his own name, Giorgio Armani. His brilliant success was influenced by the connections of the Hollywood designer. Seductive Richard Gere in the movie "American Gigolo" has clothes perfectly tailored by Emporio Armani. Costumes and creations prepared for film productions, series and for the needs of cinema stars made the brand famous and its products synonymous with highest quality, luxury and class. Emporio Armani is created The brand's success was conducive to its development. Armani created successive lines, including the slightly more financially available Emporio Armani and Armani Jeans founded in 1981. Created with the minimalism of the main Giorgio line, they conquer the world of fashion with simple, casual cuts and a timeless palette. A wide range of clothing and accessories from the line, such as an Emporio Armani t-shirt or Emporio Armani sunglasses, are available for you on the online store, Vitkac.com. Look out also for an Emporio Armani watches sale in the online store. In addition to the women's and men's clothing collection, there are also other accessories by EA. A perfect complement to the overall look is to choose a beautiful fragrance from the Emporio Armani perfume line. Timeless brand Emporio Armani's timepieces attract many fans from around the world. Created with attention to detail they guarantee perfect style and many years of use. High-quality mechanisms and top design satisfy the expectations of the most demanding customers. Emporio Armani watch - classic, subtle, decorated or even sports accesory comes down to a common denominator - elegance. The same features can be attributed to perfumes, which for years have been a rapidly growing branch of the Giorgio Armani power. The Emporio Armani line available on Vitkac.com We have prepared a wide range of products within the collection of the brand. T-shirts, jackets, trousers, jackets, shoes and accessories are waiting for you in the online store. The excellent offer of Isabel Marant, Gucci and Versace is also available on Vitkac.com.	cc/2019-30/en_head_0044.json.gz/line3387
__label__cc	0.74885	0.25115	Entertainment Featured Articles Voice Over Narration: When It’s Effective and When It’s Not July 7, 2016 July 7, 2016 Antonio Lopez 0 Comment voice over narrators Voice over narration can be a powerful add on when done properly, at the right time and with the right scene. In movies, voice over narration is when you hear a voice, usually that of the main character, narrating events as they happen or narrating a conclusion or a twist that you don’t see in the scene. Now, there are those movies where voice over narration is used just as a means to an end. Perhaps the movie was too long and they were out of time so they throw a voice over narration in hoping it wraps up the movie and the audience understood what had just happened and what the whole film was trying to convey. Sometimes it works, sometimes it doesn’t. Shawshank Redemption (1995) Bloggers Trey Morehouse and Mark Hughes agree that the voice over hampered the overall movie quality. It was a great film and most of the voiceover narration was used to ‘move the plot’ and Morgan Freeman was the voice, it also was one of the most ‘overused and overwrought’ uses of film narration. Oblivion (2013) Ryan Lambie’s blog calls the monologue in the opening of this film a lengthy exposition that does get the job done but not as elegantly. Oblivion is a sci-fi film and the movie opened explaining where the film is set and what was happening to the Earth and what the strange floating Pyramid objects were floating in the sky. As far as some audiences go, visuals and action would have been better to get them up to speed. The Big Lebowski (1998) The particular film seems to come up a quite a lot when one looks up films with good voice over narration. A famous narration line blogs like to quote is, “sometimes there’s a man, sometimes, there’s a man. Aw. I lost my train of thought here. But… aw, hell. I’ve done introduced him enough.” To this day, audiences love an off hand, kind of sarcastic narrative. Directors Joel and Ethan explain that they used a narrative voice “as if someone was commenting on the plot from an all-seeing point of view. And at the same time rediscovering the old earthiness of a Mark Twain.” It certainly worked for their film Apart from the film touching on controversial issues – what was controversial in the 70’s – the voice over narrative on this film was also that of a ruthless sociopathic killer and rapist where instead of having the audience empathize with the character, the voice is unnerving, instils fear and causes the audience to question their morality, goodness and freedom. It’s the kind of controversy that captures the audience’s interest and stays with them a long time after seeing the film and the voice over narrative in their heads, too. These are but a few films that demonstrate effective and not so effective voice overs. Some of voiceover narratives don’t work so well because they make it so obvious that what is being narrated are just remnants of the idea from the novel for movies based on a novel and on the other hand it can also work well as it provides continuity and clarity as far as what was going on the in the story. When executed properly with the plot, a voice over narrative is a powerful tool in bringing a whole picture for the film that audiences are inclined to not miss anything but sit and watch as the story unfolds. Can you think of a time a narrator added a lot of weight to the production, or when it was totally unnecessary? Let us know in the comments below. ← Staying Front of Mind in Your Voice Over Network Your Marketing Content Voiced in Different Languages →	cc/2019-30/en_head_0044.json.gz/line3388
__label__wiki	0.583924	0.583924	Confront Genocide Warnings of Catastrophe: Part I Preventing Genocide Ferencz International Justice Initiative Rwanda Video Gallery Preventing Genocide Blog Simon-Skjodt Center for the Prevention of Genocide Part II: Documents 1–5 Part III: Documents 6–10 In commemoration of the 20th anniversary of the Rwandan genocide, the Museum’s Simon-Skjodt Center for the Prevention of Genocide and the National Security Archive launched the first phase of a multiyear initiative titled Failure to Prevent: International Decision Making in the Age of Genocide. The first phase includes a series of “electronic briefing books” that provide in-depth background to pivotal events before and during the Rwandan genocide when international action could have made a difference. This is the second briefing book in the series. Concerned about the possibility of “a new bloodbath” in Rwanda, the Belgian foreign ministry issued a dramatic diplomatic demarche on February 25, 1994, calling for a strengthening of the UN peacekeeping mission in the Central African country. According to Belgian government dispatches, the initiative failed because of opposition by the United States and the United Kingdom and resistance from the UN Secretariat. Featured here are new English translations of the diplomatic traffic between Brussels and New York on the eve of the Rwandan genocide, along with a series of earlier warnings about the potential for mass violence in Rwanda from US, French, and UN sources dating back to late 1990. These postings form part of a detailed documentation of the international response to the genocide that killed between 500,000 and one million Rwandans, predominantly Tutsis, from April to July 1994. Originally published in French and Flemish as part of a Belgian Senate investigation into the Rwandan tragedy in December 1997, the Belgian diplomatic cable of February 25 describes a “significant deterioration” in the security situation that “could well lead to a new bloodbath.” It also expresses concern about the possibility that Belgian paratroopers, known as the “Blue Berets,” might become “passive witnesses to genocide in Rwanda.” Addressed to the Belgian ambassador to the United Nations, Paul Noterdaeme, the February 25 cable reflects the growing concern among senior Belgian officials over the breakdown in the Arusha peace process. It followed a sudden spate of political assassinations (external link), coinciding with Belgian Foreign Minister Willy Claes’s visit to Kigali, that threatened to torpedo attempts to install a new, national unity government. In his formal reply to Brussels three days later, Ambassador Noterdaeme reported that the United States and the United Kingdom were opposed to strengthening the United Nations Assistance Mission for Rwanda (UNAMIR) mandate and were even considering withdrawing the peacekeepers “in case of difficulties.” He added that UN Secretary-General Boutros Boutros-Ghali was opposed to any adjustment in the rules of engagement for UNAMIR, for both political and military reasons. As we approach the 20th anniversary of the Rwandan genocide, the documents published here provide further reminders of the passivity of an international community scarred by the murders of UN peacekeepers in Somalia in October 1993. Repeated warnings of catastrophe by diplomats and intelligence analysts were either missed or ignored by senior policy makers in Washington, New York, Paris, and elsewhere. Next: Documents 1–5: Summaries and Links	cc/2019-30/en_head_0044.json.gz/line3390
__label__wiki	0.586837	0.586837	Meet YWCA Toronto’s 2016 Women of Distinction Half of the federal government’s Cabinet is made up of women, but 90 per cent of women do not report sexual abuse. Investment in community infrastructure is on the agenda again, but in Toronto alone, there are 95,000 households on the social housing waiting list. While it would be wrong to claim there has been little or no improvement on so-called “women’s issues,” it would be equally erroneous to suggest that continued progress is inevitable, especially for women and girls living in poverty, fear, and isolation. The work to secure equality and social justice remains an ongoing challenge. That’s why we need to support associations like YWCA Toronto. For 140 years, YWCA Toronto has provided shelter and support to those seeking refuge from violence and abuse; offered training and resources to help women into jobs and out of poverty; increased participation and empowerment among girls; and advocated for a fairer and more equitable society. Over the past year alone, more than 6,000 women received training, job-seeking assistance and links to community resources through YWCA Toronto’s employment and skills development centres. More than 900 women and their families found permanent homes through YWCA Toronto and 1,300 women and their children were able to escape and recover from violence. Working together, YWCA Toronto was able to help 1,000 more women and young girls than the previous year. YWCA Toronto has also played host to the launch of the provincial government’s Action Plan on Sexual Violence and Harassment; advocated for better child care, poverty reduction and national housing strategies; and called for action on Truth and Reconciliation recommendations, among other things. YWCA Toronto recognizes that these results can only happen if women work together. For the past 35 years, YWCA Toronto has honoured extraordinary women who have worked tirelessly to make a difference for women and girls across the city, country, and the globe. More than 200 women have received a Women of Distinction Award since the first awards ceremony in 1981. They are game changers in their respective fields – law, education, health, culture and the arts, politics, environment, international development and corporate leadership. These women have used their talent to improve the lives of other women and young girls, and helped raise awareness about inequities in local, national, and international communities, and create systemic change. See for yourself. On May 26 YWCA Toronto is hosting the 2016 Women of Distinction Awards ceremony – the organization’s biggest fundraising event of the year. Proceeds support the over 30 programs that serve more than 12,000 women and families in the Greater Toronto area. There will be eight women receiving the honour of a Woman of Distinction award. These women are truly awe-inspiring: Roberta L. Jamieson (President’s Award) First Nations leader, highly acclaimed public figure and CEO of Indspire, Roberta has spent five decades in numerous breakthrough positions advocating for change and justice for Indigenous people and Canada. Tessa Hill and Lia Valente (Young Women of Distinction) Tessa Hill and Lia Valente were 13 when they took on rape culture as a documentary project and turned it into a successful public campaign bringing sexual consent into Ontario’s health education curriculum. Colleen Johnston (Corporate Leadership) This senior executive from TD Bank Group and women’s leadership guru has successfully championed for stronger representation of women in corporate leadership, which helped to significantly increase the number of women in TD’s executive ranks. Georgia Quartaro (Education) Georgia created innovative education programs and violence-against-women training that reaches women and marginalized groups who have experienced trauma and responds to their needs and potential. Reeta Roy (International Development) Reeta Roy saw that opportunities and conditions for girls and women farmers in African countries were disturbingly unequal to men’s. The MasterCard Foundation she heads guarantees that at least 50 percent of program participants are women and girls. Elizabeth Shilton (Law and Justice) Elizabeth argued before the Supreme Court to uphold the rape shield law; won a pay equity case ending wage inequities; defended the right of sexual assault survivors to keep their names out of the public eye; and prevented the disclosure of counselling records of sexual abuse survivors. Dr. Cheryl Wagner (Health) When HIV/AIDS first hit women, Dr. Cheryl Wagner was one of the first – and few – Toronto physicians to whom they could turn for expertise, help and health care. She extended her work to include researching and advocating for services to address their distinct needs. Celebrate these women and what they have accomplished! To get your tickets to the exciting event at The Carlu (444 Yonge St.), visit www.womenofdistinction.ca. Author Katherine DeClerq Katherine DeClerq is a contributor to Women's Post. Her previous writing experience includes the Toronto Star, Maclean's Magazine, CTVNews, and BlogTO. She can often be found at a coffee shop with her MacBook computer. Despite what CP says, she is a fan of the Oxford comma. Beth Shaw founder of YogaFit Tonga on my mind Blind financial professional banks on her guide dog to help her thrive in busy career	cc/2019-30/en_head_0044.json.gz/line3397
__label__wiki	0.602977	0.602977	BAILEYS WOMEN’S PRIZE FOR FICTION ANNOUNCES 2017 JUDGING PANEL London, Thursday 20 October 2016: The judges for the 2017 Baileys Women’s Prize for Fiction – the UK’s most prestigious annual book award for fiction written by a woman, now in its 22nd year – are announced today. Chair of Judges, Tessa Ross, CEO House Productions, is joined by Sam Baker, journalist, author and co-founder of The Pool; Katie Derham, presenter and broadcaster; Aminatta Forna, award-winning novelist, memoirist and essayist and Sara Pascoe, comic and author. “I’m honoured to be chairing this year’s Baileys Women’s Prize for Fiction,” commented Tessa Ross, “As well as the great pleasure of spending time with four very talented judges, I’m thrilled to be part of this celebration of great writing and very much look forward to it.” Established in 1996 to celebrate and promote international fiction by women throughout the world to the widest range of readers possible, the Baileys Women’s Prize for Fiction is awarded for the best novel of the year written by a woman. Any woman writing in English – whatever her nationality, country of residence, age or subject matter – is eligible. The winner will receive an anonymously endowed cheque for £30,000 and a limited edition bronze figurine known as a ‘Bessie’, created and donated by the artist Grizel Niven. The 2017 Baileys Women’s Prize for Fiction will be awarded on June 7th 2017 at the Royal Festival Hall, Southbank Centre, London. Previous winners include Lisa McInerney for The Glorious Heresies (2016), Ali Smith for How to be Both (2015), Eimear McBride for A Girl is a Half-formed Thing (2014), A.M. Homes for May We Be Forgiven (2013), Madeline Miller for The Song of Achilles (2012), Téa Obreht for The Tiger’s Wife (2011), Barbara Kingsolver for The Lacuna (2010), Marilynne Robinson for Home (2009), Rose Tremain for The Road Home (2008), Chimamanda Ngozi Adichie for Half of a Yellow Sun (2007), Zadie Smith for On Beauty (2006), Lionel Shriver for We Need to Talk About Kevin (2005), Andrea Levy for Small Island (2004), Valerie Martin for Property (2003), Ann Patchett for Bel Canto (2002), Kate Grenville for The Idea of Perfection (2001), Linda Grant for When I Lived in Modern Times (2000), Suzanne Berne for A Crime in the Neighbourhood (1999), Carol Shields for Larry’s Party (1998), Anne Michaels for Fugitive Pieces (1997), and Helen Dunmore for A Spell of Winter (1996). For the Baileys Women’s Prize for Fiction 2017, novels must be published in the UK between 1st April 2016 and 31st March 2017. The Prize is administered by the Society of Authors. For press enquiries, please contact Jane Acton or Georgina Church at Kallaway: Email: womensprizeforfiction@kallaway.com WOMEN’S PRIZE FOR FICTION OFFERS SPONSORSHIP OPPORTUNITY FOR 2018 SOCIETY OF AUTHORS TO ADMINISTER THE BAILEYS WOMEN’S PRIZE FOR FICTION	cc/2019-30/en_head_0044.json.gz/line3398
__label__wiki	0.73982	0.73982	Countries With The Largest Aging Population In The World Known for its increasing number of elderly, Japan has the most aged citizens in its borders, with Italy close behind. An elderly Japanese couple hitting the weights. Home to many supercentenarians, 26.3% of the island nation's population is 65 years of age or older. The world is aging rather rapidly. However, there are a few countries, such as Japan and Italy, that stand out from among the rest, due to the immense proportions of their citizens over 65 years of age. According to the World Health Organization, nearly two billion people across the world are expected to be over 60 years old by 2050, a figure that’s more than triple what it was in 2000. Because of such increases in their aging populations, some of the world’s largest economies have started facing subsequent increases in their health-care costs, higher pension costs, and a decreasing proportion of their respective citizenries active in the workforce. A major contributing factor to this trend has been diminishing fertility rates in these countries in recent decades, further compounded by longer lifespans. In order to adapt to their increasingly aging populations, many countries have raised the retirement age, reduced pension benefits, and have started spending more on elderly care. With lesser numbers of individuals entering the population and people living much longer lives, people above the age of 65 now make up an increasing share of the world’s total population. We take at look at those countries which are particularly well-known for their rapidly rising numbers of aging citizens. Countries With the Largest Aging Populations Which Country Has the Oldest Population? With 27% of its population over the age of 65, Japan has the oldest population in the world. Japan is home to the oldest citizenry in the world, with 27% of its population being 65 years of age or older. In the year 2014, the percentage was about 25.8%, which shows that the number is steadily rising each year. It is predicted that nearly a third of the Japanese people (32.2%) will be senior citizens by 2030. At the present moment, more than one in four people in the country are over the age of 65, whereas the country’s population aged between 15 and 64 fell by 4% between 2000 and 2010. Next on this list is Italy, with 23% of its population being 65 years of age or older. The country’s elderly population is known to have remained at around 20% in the period between 2005 and 2010, but has steadily been on the rise in the few years since. Most interestingly, and in line with these figures, the younger population of people aged between 0 and 14 has not exhibited growth since 1999, and remained at a mere 14% until recently. Largely due to its aging populace, Italy is known to have the highest relative public spending on pensions of any country in the EU. Pensions take over 16% of Italy's GDP, as compared to 11% for the rest of the European Union. Portugal is next on this list, as 22% of its population is over 65 years of age. The average age of retirement in the country is 66 years of age. Part of the reason why Portugal has a high rate of elderly citizens is because many pensioners from colder countries within the EU may choose to retire in the sunny country. Other Countries with Rising Numbers of Older Citizens There are quite a few others countries that have high percentages of their citizens aged 65 years and over as well. Some of these are Germany, Finland, Bulgaria, Sweden, Latvia and Malta. Their statistics indicate that 21%, 21%, 21%, 20%, 20%, and 19% of their respective populations are 65 years of age or older. Countries With The Elderly Population In The World % of population over 65 years old 1 Japan 27 2 Italy 23 3 Portugal 22 4 Germany 21 5 Finland 21 6 Bulgaria 21 7 Greece 20 8 Sweden 20 9 Latvia 20 10 Croatia 20 11 France 20 12 Denmark 20 13 Estonia 19 14 Spain 19 15 Malta 19 16 Austria 19 17 Slovenia 19 18 Czech Republic 19 19 Lithuania 19 20 Netherlands 19 21 Hungary 19 22 Belgium 19 23 United Kingdom 19 24 Switzerland 18 25 Romania 18 This page was last updated on April 25, 2017. By Faraz Haider Countries By Percentage of World Population Top Countries Of The World By Zoroastrian Population European Countries By Population Density Countries With the Lowest Population Density What Percentage of the World's Population Has Brown Hair?	cc/2019-30/en_head_0044.json.gz/line3399
__label__wiki	0.883835	0.883835	Individual Investors Shift Assets to Stocks Brokers Report Near-Record Trading Activity, Investment Flows; Moving Out of Real Estate Jane J. Kim and Jeff D. Opdyke Individual investors are moving into the stock market at a stronger clip than seen in years. The number of trades by individual investors has risen substantially at discount brokerage firms in recent months and jumped an estimated 30% to 40% in January from December. The discount firms, which offer lower-priced trades, also report that money flowing into stock mutual funds last month was at a near record level. Charles Schwab Corp. , for example, saw $4.5 billion flow into its stock mutual funds last month, the highest amount since February 2000, when net investments hit $4.7 billion. Other financial-services companies also say they are seeing greater activity among individual investors, although many of these firms don't disclose detailed data on a monthly basis. At Citigroup Inc., C -0.70% the Smith Barney Consulting Group division, which provides fee-based managed accounts, says investment flows into stocks so far this year are "substantially" higher than they were in 2005 and 2004. St. Louis-based brokerage firm Edward Jones saw new account openings in January rise 11% from a year ago, and says February growth is also strong. At Fidelity Investments, net flows into stock mutual funds soared to $5.6 billion in January from $400 million a year ago. Fidelity says the investments represent new money coming in, as well as a reallocation of cash sitting in investors' brokerage accounts. Rallying markets have piqued interest. The Dow Jones Industrial Average is up 3.92% so far this year. Yesterday, stocks rose strongly despite a report that the consumer price index jumped 0.7% in January from the previous month. Investors took heart, however, because the key inflation measure was up just 0.2%, excluding the volatile energy and food indexes. The Dow Jones industrials rose 68.11 points to 11137.17, its highest level in nearly five years. Retail investors are being drawn to stocks partly because of weakening returns from some other investments such as real estate and bonds, which have suffered as the Federal Reserve continues to raise short-term interest rates. Indeed, net inflows into bond funds so far this year are only half of what they were a year ago. Even investors' appetite for cash-like investments appears to be waning, despite yields of as much as 4% or even higher. Assets in money-market mutual funds, for example, were up only $4.1 billion last month compared with average January inflows of $33.4 billion for the past 10 years, according to iMoneyNet.com. Moving Back Individual investors are putting more money into stock markets. Here are some reasons: Other investments, including real estate and bonds, are weakening. U.S. blue-chip stocks are up strongly, with the Dow Jones Industrial Average ahead 3.92% so far this year. International markets have shown superior performance. Aging boomers and others increasingly are focused on saving for retirement. Bruce McMeikan of Newport Beach, Calif., says he is in the process of selling one of his rental properties and putting the proceeds into the stock market. He also recently opened brokerage accounts at ETrade Financial Corp. ET 0.74% for his two daughters in December. "We feel the housing market will take a bit of a downturn for a while," says the 56-year-old, who runs a company in the high-tech industry. The biggest thing that could possibly put a damper on the stock market is a terrorist attack, he says. If that doesn't happen, Mr. McMeikan says he believes the outlook for stocks is good. To be sure, not all financial firms are seeing the return of the retail investor. Prudential Financial Inc. PRU -1.94% says it hasn't experienced a substantial increase in new accounts or mutual-fund inflows. Edward Jones says many of its clients are seeking safer returns by purchasing certificates of deposit, especially with today's relatively high short-term interest rates. Other firms say investors today have learned a lesson from the Internet bubble of the late 1990s and are more careful about how they invest in stocks. For example, there is increased interest in investments that automatically diversify investors' holdings. Sales of AIM Investments' asset-allocation funds, in which a single portfolio holds multiple types of investments, are up 50% "and gaining momentum," says Jim Stueve, AIM's director of retail sales. More investors are also using options, a type of financial contract whose value is based on some underlying investment, as a way to hedge their stock risk, says ETrade President R. Jarrett Lilien. Options as a percentage of E*Trade's overall trading volume was 11.2% at the end of the fourth quarter, compared with 5.6% at the end of 2002. Much of the interest in stocks appears to be going overseas. International equity funds, a sector that represents only 15% of total assets among all stock mutual funds, captured about 80% of the inflows into stock funds so far this year, according to AMG Data Services of Arcata, Calif. In fact, four of the five mutual funds that saw the biggest inflows last month were international funds, including Fidelity Diversified International, American Funds' Capital World Growth and Income Fund (Class A shares), Dodge & Cox International Stock, and the JPMorgan International Equity Fund JPM -0.98% (Select shares), according to AMG. International funds are the top-selling investment at AIM Investments these days, continuing a trend that began last year. In the last seven weeks, gross weekly sales of AIM's Developing Markets fund, which invests in Russia, Brazil and Egypt, among other places, are up nearly 500% from last year's weekly average, the company says. AIM's International Growth and European Growth funds also are up strongly, it says. Foreign stocks' appeal stems in part from their recent superior performance. The Morgan Stanley Capital International EAFE Index, a broad measure of stocks in Europe, Australia and the more-developed parts of Asia, last year gained 26% in local-currency terms (or 11% when converted into U.S. dollars), outpacing the S&P 500 Index's 3% rise. For U.S. investors, greater exposure to foreign markets can heighten volatility in the near-term, partly because of the risk of sudden movements in currency exchange rates. What's more, some analysts say that the foreign-stock sector has already seen strong investor interest and is getting expensive. Domestic retail trading volumes have steadily climbed since hitting a low in February 2003, according to an analysis by Sanford C. Bernstein & Co., a unit of Alliance Capital Management LP, and are approaching levels last seen in 2001 before the market crash. Although active traders were the first ones to return to the market, "now we're beginning to see the core investors come back -- the families, the 40-year-olds with kids and retirees," says Bernstein senior analyst Brad Hintz. Branch managers for retail brokerage firms are reporting an increase in new account openings. Piper Jaffray Co PJC -0.83% s.' Wayzata, Minn., branch has had a "substantial" increase in assets under management as new clients sign up and current clients bring over more cash, says Mark Eckerline, senior vice president of investments. The discount brokerage firms, which represent an estimated 8% of all retail commissions, say they are seeing a record level of activity, and many of them are rolling out promotions offering free trades and cash back to get investors to open accounts. OptionsXpress Holdings Inc. reported a record level of trades, new account openings, and assets last month. At TD Ameritrade Holding Corp., trades from just the Ameritrade business, which recently merged with TD Waterhouse, were up 32% last month from December, the second highest month-to-month increase since 1999. (The previous peak was January 2004, when trading volume rose 44%.) Online brokerage firm ShareBuilder Corp. says it opened more than 40,000 new accounts in January -- the highest number since 1999. Write to Jane J. Kim at jane.kim@wsj.com and Jeff D. Opdyke at jeff.opdyke@wsj.com	cc/2019-30/en_head_0044.json.gz/line3402
__label__wiki	0.967592	0.967592	US Sen. Amy Klobuchar joins 2020 Democratic race Updated: 6:11 AM CST Feb 11, 2019 Democratic Sen. Amy Klobuchar, of Minnesota, announced Sunday she's joining the 2020 presidential race, becoming the most prominent Midwestern candidate as the party tries to win back voters in a region that helped put Donald Trump in the White House."I'm asking you to join us on this campaign," she said in remarks released before her afternoon announcement at an event along the Mississippi River in Minneapolis. Klobuchar, who already is scheduled to speak Feb. 21 in Iowa, site of the nation's first caucuses on the nominating calendar, says she doesn't have "a political machine" and doesn't "come from money," but she says she does have "grit."She is citing the need to "heal the heart of our democracy and renew our commitment to the common good," according to her prepared remarks.An exuberant crowd gathered on a cold and snowy day at a park along the Mississippi River waterfront with the city's skyline in the background. Campaign volunteers passed out hand warmers along with American flags, as well as cookies and copious amounts of hot chocolate and apple cider. Supporters gathered around heat lamps and bonfires as they waited for the senator to speak.Klobuchar, who easily won a third term last year, has pointed to her broad appeal across Minnesota as she has discussed a 2020 run. She has drawn support from voters in urban, suburban and rural areas, including in dozens of counties Trump won in 2016.She has said that success could translate to other Midwestern states such as Michigan and Wisconsin, reliably Democratic in presidential races for decades until Trump's victory over Hillary Clinton.The list of Democrats already in the race features several better-known senators with the ability to raise huge amounts of money — Elizabeth Warren, of Massachusetts, Kamala Harris, of California, Cory Booker, of New Jersey, and Kirsten Gillibrand, of New York.The field soon could expand to include prominent Democrats such as former Vice President Joe Biden.A Des Moines Register/CNN/Mediacom poll conducted by Selzer & Company in December found that Klobuchar was largely unfamiliar to likely Iowa caucusgoers, with 54 percent saying they didn't know enough about her to have an opinion, while 38 percent had a favorable opinion and 8 percent had an unfavorable opinion."She starts out perhaps with a better understanding of Midwestern voters, but I think she faces the same hurdles every one of them face, which is: Are Iowans going to find them either the best candidate to defeat Donald Trump or the candidate that most aligns with their ideologies and issues?" said John Norris, a longtime Iowa-based Democratic strategist. "I don't know that coming from Minnesota gives her any advantage with Iowans."Klobuchar, 58, is known as a straight-shooting pragmatist willing to work with Republicans, making her one of the Senate's most productive members at passing legislation.The backdrop for her rally was the Interstate 35 bridge over the Mississippi. The span was built after the previous bridge collapsed in 2007, killing 13 people. Klobuchar had worked with then-Sen. Norm Coleman, R-Minn., to help fund the new bridge and get it completed at a faster-than-usual pace, and she has cited it as an example of achieving results through bipartisan cooperation."We worked across the aisle to get the federal funding and we rebuilt that I-35W bridge — in just over a year. That's community. That's a shared story. That's ordinary people doing extraordinary things," she says in her prepared remarks."But that sense of community is fracturing across our nation right now, worn down by the petty and vicious nature of our politics. We are all tired of the shutdowns and the putdowns, the gridlock and the grandstanding. Our nation must be governed not from chaos but from opportunity. Not by wallowing over what's wrong, but (by) marching inexorably toward what's right," she says.Klobuchar's focus in recent months has included prescription drug prices, a new farm bill and election security. She supports the Green New Deal, a Democratic plan proposed this past week to combat climate change and create thousands of jobs in renewable energy.But her legislative record has drawn criticism from both the GOP and some fellow Democrats. Some Republicans say Klobuchar is able to get things done because she pushes smaller issues. Some progressives say she lacks the kind of fire and bold ideas needed to bring significant change and excite voters.Klobuchar, a lawyer and the former prosecutor in Minnesota's largest county, raised her national profile during a Senate Judiciary Committee hearing last fall for Supreme Court nominee Brett Kavanaugh, who was accused of sexually assaulting a woman when they were both in high school.When Klobuchar asked Kavanaugh whether he ever had had so much to drink that he didn't remember what happened, he turned the question around. He asked Klobuchar, "Have you?"Unruffled, Klobuchar continued as Kavanaugh asked again. Kavanaugh later apologized to Klobuchar, whose father is an alcoholic."When you have a parent who's an alcoholic, you're pretty careful about drinking," she said. "I was truly trying to get to the bottom of the facts and the evidence."Among the other Midwestern lawmakers who could also seek the nomination are Sen. Sherrod Brown, of Ohio, who has been visiting early-voting states, and Pete Buttigieg, the mayor of South Bend, Indiana, who established an exploratory committee last month.Klobuchar campaigned with Democrats in Iowa last fall, and in December, she spoke to progressive farmers and activists about the importance of bridging the divide between urban and rural areas. She said the lesson learned after the 2016 election was "we are not going to leave the Midwest behind.""This is the moment for the Midwest," she said, "and we don't want to be forgotten again in a national election."___AP polling editor Emily Swanson in Washington contributed to this report. MINNEAPOLIS (AP) — Democratic Sen. Amy Klobuchar, of Minnesota, announced Sunday she's joining the 2020 presidential race, becoming the most prominent Midwestern candidate as the party tries to win back voters in a region that helped put Donald Trump in the White House. "I'm asking you to join us on this campaign," she said in remarks released before her afternoon announcement at an event along the Mississippi River in Minneapolis. Klobuchar, who already is scheduled to speak Feb. 21 in Iowa, site of the nation's first caucuses on the nominating calendar, says she doesn't have "a political machine" and doesn't "come from money," but she says she does have "grit." She is citing the need to "heal the heart of our democracy and renew our commitment to the common good," according to her prepared remarks. An exuberant crowd gathered on a cold and snowy day at a park along the Mississippi River waterfront with the city's skyline in the background. Campaign volunteers passed out hand warmers along with American flags, as well as cookies and copious amounts of hot chocolate and apple cider. Supporters gathered around heat lamps and bonfires as they waited for the senator to speak. Klobuchar, who easily won a third term last year, has pointed to her broad appeal across Minnesota as she has discussed a 2020 run. She has drawn support from voters in urban, suburban and rural areas, including in dozens of counties Trump won in 2016. She has said that success could translate to other Midwestern states such as Michigan and Wisconsin, reliably Democratic in presidential races for decades until Trump's victory over Hillary Clinton. The list of Democrats already in the race features several better-known senators with the ability to raise huge amounts of money — Elizabeth Warren, of Massachusetts, Kamala Harris, of California, Cory Booker, of New Jersey, and Kirsten Gillibrand, of New York. The field soon could expand to include prominent Democrats such as former Vice President Joe Biden. A Des Moines Register/CNN/Mediacom poll conducted by Selzer & Company in December found that Klobuchar was largely unfamiliar to likely Iowa caucusgoers, with 54 percent saying they didn't know enough about her to have an opinion, while 38 percent had a favorable opinion and 8 percent had an unfavorable opinion. "She starts out perhaps with a better understanding of Midwestern voters, but I think she faces the same hurdles every one of them face, which is: Are Iowans going to find them either the best candidate to defeat Donald Trump or the candidate that most aligns with their ideologies and issues?" said John Norris, a longtime Iowa-based Democratic strategist. "I don't know that coming from Minnesota gives her any advantage with Iowans." Klobuchar, 58, is known as a straight-shooting pragmatist willing to work with Republicans, making her one of the Senate's most productive members at passing legislation. The backdrop for her rally was the Interstate 35 bridge over the Mississippi. The span was built after the previous bridge collapsed in 2007, killing 13 people. Klobuchar had worked with then-Sen. Norm Coleman, R-Minn., to help fund the new bridge and get it completed at a faster-than-usual pace, and she has cited it as an example of achieving results through bipartisan cooperation. "We worked across the aisle to get the federal funding and we rebuilt that I-35W bridge — in just over a year. That's community. That's a shared story. That's ordinary people doing extraordinary things," she says in her prepared remarks. "But that sense of community is fracturing across our nation right now, worn down by the petty and vicious nature of our politics. We are all tired of the shutdowns and the putdowns, the gridlock and the grandstanding. Our nation must be governed not from chaos but from opportunity. Not by wallowing over what's wrong, but (by) marching inexorably toward what's right," she says. Klobuchar's focus in recent months has included prescription drug prices, a new farm bill and election security. She supports the Green New Deal, a Democratic plan proposed this past week to combat climate change and create thousands of jobs in renewable energy. But her legislative record has drawn criticism from both the GOP and some fellow Democrats. Some Republicans say Klobuchar is able to get things done because she pushes smaller issues. Some progressives say she lacks the kind of fire and bold ideas needed to bring significant change and excite voters. Klobuchar, a lawyer and the former prosecutor in Minnesota's largest county, raised her national profile during a Senate Judiciary Committee hearing last fall for Supreme Court nominee Brett Kavanaugh, who was accused of sexually assaulting a woman when they were both in high school. When Klobuchar asked Kavanaugh whether he ever had had so much to drink that he didn't remember what happened, he turned the question around. He asked Klobuchar, "Have you?" Unruffled, Klobuchar continued as Kavanaugh asked again. Kavanaugh later apologized to Klobuchar, whose father is an alcoholic. "When you have a parent who's an alcoholic, you're pretty careful about drinking," she said. "I was truly trying to get to the bottom of the facts and the evidence." Among the other Midwestern lawmakers who could also seek the nomination are Sen. Sherrod Brown, of Ohio, who has been visiting early-voting states, and Pete Buttigieg, the mayor of South Bend, Indiana, who established an exploratory committee last month. Klobuchar campaigned with Democrats in Iowa last fall, and in December, she spoke to progressive farmers and activists about the importance of bridging the divide between urban and rural areas. She said the lesson learned after the 2016 election was "we are not going to leave the Midwest behind." "This is the moment for the Midwest," she said, "and we don't want to be forgotten again in a national election." AP polling editor Emily Swanson in Washington contributed to this report.	cc/2019-30/en_head_0044.json.gz/line3403
__label__wiki	0.870892	0.870892	Woman beats DUI rap with claim her body brews alcohol by: Adam Staten Posted: Dec 30, 2015 / 10:20 PM UTC / Updated: Jun 27, 2019 / 04:15 PM UTC ALBANY, N.Y. (AP) – Drunken-driving charges against an upstate New York woman have been dismissed based on an unusual defense: Her body is a brewery. The woman was arrested while driving with a blood-alcohol level more than four times the legal limit. She then discovered she has a rare condition called “auto-brewery syndrome,” in which her digestive system converts ordinary food into alcohol, her lawyer Joseph Marusak said in interviews this week. A town judge in the Buffalo suburb of Hamburg dismissed the drunken-driving charges this month after Marusak presented a doctor’s research showing the woman had the previously undiagnosed condition in which high levels of yeast in her intestines fermented high-carbohydrate foods into alcohol. The rare condition, also known as gut fermentation syndrome, was first documented in the 1970s in Japan, and both medical and legal experts in the U.S. say it is being raised more frequently in drunken-driving cases as it is becomes more known. “At first glance, it seems like a get-out-of-jail-free card,” said Jonathan Turley, a law professor at George Washington University. “But it’s not that easy. Courts tend to be skeptical of such claims. You have to be able to document the syndrome through recognized testing.” The condition was first documented in the U.S. by Barbara Cordell of Panola College in Texas, who published a case study in 2013 of a 61-year-old man who had been experiencing episodes of debilitating drunkenness without drinking liquor. Marusak contacted Cordell for help with his client who insisted she hadn’t had more than three drinks in the six hours before she was pulled over for erratic driving Oct. 11, 2014. The woman was charged with driving while intoxicated when a Breathalyzer test showed her blood-alcohol content to be 0.33 percent. Cordell referred Marusak to Dr. Anup Kanodia of Columbus, Ohio, who eventually diagnosed the woman with auto-brewery syndrome and prescribed a low-carbohydrate diet that brought the situation under control. She is currently free to drive without restrictions. During the long wait for an appointment, Marusak arranged to have two nurses and a physician’s assistant monitor his client for a day to document she drank no alcohol, and to take several blood samples for testing. “At the end of the day, she had a blood-alcohol content of .36 without drinking any alcoholic beverages,” Marusak said. He said the woman also bought a Breathalyzer and blew into it every night for 18 days, registering around .20 every time. The legal threshold for drunkenness in New York is 0.08. While people in cases described by Cordell sought help because they felt drunk and didn’t know why, Marusak said that’s not true of his client. “She had no idea she had this condition. Never felt tipsy. Nothing,” he said. Marusak submitted medical evidence of his client’s condition to the judge, who dismissed the DWI charges Dec. 9. Assistant Erie County District Attorney Christopher Belling said the matter is being reviewed and his office doesn’t comment on open cases. Marusak declined to name the woman, citing medical confidentiality laws. He said the case has been sealed since the charges were dropped. The Buffalo News described her as a 35-year-old school teacher, and quoted the arresting officer as saying she had bloodshot eyes, slurred speech, and failed several field sobriety tests. Turley noted that auto-brewery syndrome was only a valid defense in this case because the woman was unaware she had it. He said courts have long recognized that people who know they have medical conditions can be found liable for failing to take reasonable measures in light of that knowledge. Kanodia, the Ohio doctor, said two DWI cases where auto-brewery syndrome is being used as a defense are currently being tried in Texas and Oregon.	cc/2019-30/en_head_0044.json.gz/line3409
__label__wiki	0.707399	0.707399	Some Carter Co. roads are still closed due to February’s heavy rain CARTER CO. Tenn. (WJHL)- More than four months after parts of Carter County roads were damaged by heavy rains, some roads still remain closed. Back in February, a portion of Riverview Drive gave way after record rainfall throughout the region. Today the road is looking even worse compared to back in February. Chief Administrative Officer for the Carter County Highway Department, Roger Colbaugh, says that’s because the road keeps on sliding down towards the river. “Underneath the roadway, there is a solid rock that’s pretty deep into the ground. That’s causing water to run on it with the fill material on top of that, which is just dirt and it’s washing away and sliding down toward the river,” said Colbaugh. Colbaugh said that Riverview Drive was one of 90 roads that were damaged in Carter County during the heavy flooding. Norman Evans lives on Riverview Drive where his route to Hampton has been temporarily closed. “I’ve lived here for about six years and I come through here about twice a day. The kids’ grandmother lives over there in Hampton. It’s a quicker back and forth to Hampton from Elizabethton,” he said. The Carter County Commission voted to use $62,000 to hire a contractor or an engineering firm to design a repair plan for the road. Vice-Chair of Carter County’s Budget Committee, Isaiah Grindstaff, sending News Channel 11 the following statement, After the tremendous amount of rain that fell in February, that caused severe flooding in parts of our county, we were left with several repairs. One of which, was the damage done to Riverview Road in the Valley Forge / Eastside Communities. What started as a small road washout has quickly turned into over half of the road falling down the mountainside. Our Highway Department was quick to respond and with their hard work was quickly able to contact Mattern and Craig and obtain pricing to begin the repair process. A contract for Engineering Service was approved at a cost of $62,000 by the Commission at our April Meeting. It is my understanding that this process will hopefully be finished by the end of July. This will allow for the Highway Department to put out an RFP sometime in August for contractor services to complete the repairs necessary. The cost to repair the roadway and sure up the mountainside are estimated to be between $300,000 to $400,000. However, we are expecting that up to 75% of those funds will be reimbursed by FEMA. We are hopeful that work will begin around the end of August, beginning of September timeframe with overall completion expected to be by the end of the year or early 2020 depending upon weather. I want to thank Roger Colbaugh and the Highway Department for diligently working on this road repair project. Isaiah Grindstaff Colbaugh hopes that by the end of July or early August they will have a contract and a design with work starting the beginning of September. FEMA will be paying for most of the repairs to Riverview Drive along with roads that have already been fully repaired like Lick Skillet Road. Other roads that are still needing to be repaired in Carter County are Andrew Phenyl, Riverview Road, and Whaley Town Road according to Colbaugh. by Justin Soto / Jul 18, 2019 WISE COUNTY, Va. (WJHL) - It's been nearly 3 years since investigators say Janina Jefferson was murdered by her ex-husband Eric Jones in Appalachia, Virginia. Eric Jones is accused of shooting and killing Jefferson on November 27, 2016 at the Town of Appalachia Water Treatment Plant where she worked. by Pheben Kassahun / Jul 17, 2019 TENNESSEE (WJHL/ABC Tri-Cities) - From Florida to Tennessee, law enforcement officials serving the Southeastern U.S. will be ramping up enforcement of life-saving traffic safety laws. This is the third consecutive year, the Volunteer State is among five states joining forces to keep bad driving behavior at bay. FALL BRANCH, Tenn. (ABC Tri-Cities) - A Tennessee State Trooper is being honored for not only what he does on the clock, but off. We are introducing you to Sergeant David Osborne, who is a Marine Corps Veteran, a 20-year Tennessee Highway Patrol (THP) officer and community hero.	cc/2019-30/en_head_0044.json.gz/line3410
__label__cc	0.65898	0.34102	Leveraging Cognitive Measures in Clinical Trials Clinical Trials, Life Sciences, Pharmaceutical, This webinar will discuss the assessment of cognitive function throughout the development of drugs for both CNS and non-CNS indications. It will include a discussion of methodological considerations for the design of clinical trials and approaches to the analysis and interpretation of cognitive outcome measures for the evaluation of both drug efficacy and safety. Key Discussion Points: What do we mean by cognition? Why monitor cognition in drug development? How do we measure cognition? The current regulatory landscape Desirable characteristics of cognitive assessment tools The CANTAB Connect touchscreen cloud-based platform Future developments in cognitive assessment Cognition refers to a range of mental processes relating to the acquisition, storage, manipulation, and retrieval of information. Cognitive functioning is critical for day-to-day life, governing our thoughts and actions. It allows us to understand information about the world around us and interact safely with our environment. Cognition can be separated into multiple distinct functions, dependent on particular brain circuits and neuromodulators. Computerized cognitive tests have been developed and validated for the objective measurement of distinct cognitive abilities, such as working memory, inhibition, cognitive flexibility, and executive planning that map to particular brain regions. The accurate measurement of specific aspects of cognitive function is essential for the evaluation of the efficacy of new medications being developed to treat some of our most feared and devastating medical conditions such as Alzheimer’s disease, depression, schizophrenia and ADHD. The ability to test, measure and monitor cognitive performance over time opens up the opportunity for patients to be identified earlier and more accurately, the evaluation of new treatments faster and more efficiently, and to improve decision making throughout the development process. Cognitive impairment is increasingly recognized as an important potential side effect of medication. For example, several recent epidemiological studies have highlighted that use of commonly-used drugs with anticholinergic activity is associated with poor cognitive performance, mild cognitive impairment or even a diagnosis of dementia. However, despite concerns voiced by physicians, regulators and consumers, many drug development programs do not incorporate objective and sensitive cognitive assessments as part of the clinical characterization and decision-making process. In addition, many common medical conditions, both CNS and non-CNS disorders, including for example cardiovascular disease and diabetes, have associated cognitive deficits as part their underlying disease etiology. These cognitive deficits themselves represent important therapeutic targets, as drugs being developed to treat the disease process may also demonstrate reversal of the cognitive impairment. It is also important to consider that any drug that crosses the blood-brain barrier (BBB) can produce cognitive effects that can interfere with everyday functioning. This includes drugs for both CNS and non-CNS indications (e.g. cardiovascular drugs; including statins, diabetes, oncology, HIV, pain, antihistamines, anticonvulsants and antimuscarinics). Common disease states, environmental toxins, certain medications and the aging process itself can compromise the integrity of the BBB. It is therefore of critical importance for drug makers to monitor cognitive function throughout the drug development process and to consider the impact of their target patient populations, comorbid medical conditions and concomitant drug treatments in assessing the safety and risk profile of their drugs. This presentation will also discuss methodological considerations for cognitive assessment in clinical trials and approaches to the analysis and interpretation of cognitive outcome measures. Viewers of the webinar will leave with a firm understanding of how current state-of-the-art cognitive assessment technology can be incorporated into the clinical development process to facilitate early decision making, evaluate cognitive efficacy, profile safety and tolerability and satisfy regulatory requirements in an increasingly challenging and competitive pharmaceutical landscape. Kenton Zavitz, PhD, Director of Clinical Affairs, Cambridge Cognition Kenton has over 16 years of biotechnology and Pharmaceutical experience with involvement in all aspects of the industry from drug discovery and clinical development through to pre-commercialization. Prior to joining Cambridge Cognition, Kenton served as Chief Scientific Officer for biotech Zocere Inc. where he worked on developing a neuroprotectant drug designed to combat brain injury resulting from stroke. He currently serves on the Scientific Advisory Board for Exonate Limited, a start-up founded in 2013 at the University of Nottingham. From 1998 to 2012, Kenton worked at Myriad Pharmaceuticals, Inc. in Salt Lake City and served in a variety of roles including Senior Director of Clinical Affairs, Chief Scientist of the tarenflurbil clinical development program (an investigational drug for the treatment of Alzheimer’s disease, developed through Phase 3), Director of Neurodegeneration Therapeutics Discovery and Director of Strategic In-licensing and Scientific Evaluation. Kenton received his PhD in Biochemistry and Molecular Biology from The Sloan-Kettering Division of the Weill Cornell Graduate School of Medical Sciences in New York City. He was a Postdoctoral Fellow at the UCLA School of Medicine and was awarded fellowships from the Leukemia Society of America and the Jane Coffin Childs Memorial Fund for Medical Research. Message Presenter Have questions or would like more information? Use the form below to send a message. This webinar is designed for pharmaceutical and biotech research professionals, particularly those involved in central nervous system (CNS) drug development, where cognition is used as a measure of drug safety or efficacy, including scientists, program and project managers, directors, executives, and others involved in basic or clinical research in the CNS area. Xtalks Partner Cambridge Cognition Cambridge Cognition is a global science technology company supporting thousands of universities, healthcare providers, and companies in the Pharmaceutical and biotech industry with touchscreen cognitive assessment products and services to improve mental health research, drug development and patient well being. For more information visit www.cambridgecognition.com or contact info@cantab.com. Related Webinars Cognitive Safety: Satisfying Regulatory Requirements in a Competitive Landscape Digital Health: Optimizing Clinical Trials with Patient-Centric Technology Early Alzheimer’s Disease: Finding the Right Patients for Clinical Trials and Beyond Schizophrenia Trials: Overcoming Methodological Challenges to Enhance Study Success Understanding the Clinical Assessment of Abuse Potential during CNS Drug Development You Must Login To Register for this Free Webinar Already have an account? LOGIN HERE. If you don’t have an account you need to create a free account.	cc/2019-30/en_head_0044.json.gz/line3412
__label__wiki	0.564479	0.564479	Yonge + St. Clair Signs of Life: The Revitalization of Yonge + St. Clair National Post’s Chris Selley said he ‘was downright astonished at the state of the joint.’ City Councillor Josh Matlow said it’s now just ‘a place between Yonge and Eglinton and Bloor.’ Vice President of the Deer Park Residents Association David Cameronsmith told the paper ‘it’s just gone to hell in a handcart.’ Yonge + St. Clair has been overlooked for decades, but it wasn’t always that way. It was once regarded as a vibrant and bustling place – it was a scene. It was the home of Glenn Gould; it was a fashion centre; it was fur coats and martini drinking. It has always been the gateway to some of Toronto’s most prominent neighbourhoods. It sits on top of an important transit hub. It is historically important. All of the ingredients are there to create a neighbourhood that is again a destination in and of itself. As reported by Bisnow, Slate Asset Management has acquired 8 office towers in the heart of the neighbourhood, including those that occupy the 4 corners of its namesake intersection. ‘We have an opportunity’, Lucas Manuel of Slate Asset Management, told the National Post, ‘to make some big and fast and consolidated changes to the neighbourhood, which is our goal.’ And the changes are indeed coming fast. The first phase of development at 2 St. Clair East has begun under the direction of award-winning, San Francisco-based architecture firm Gensler. An 8-storey mural by Sheffield’s renowned Phlegm now adorns the western wall of 1 St. Clair West. Vancouver-based independent coffee roasters JJ Bean are set to open one of their first Toronto retail outposts in a custom-built house in the lobby of 2 St. Clair West. And this is just the beginning. Future plans include renovations to building lobbies and exteriors, modernizing every elevator in the neighbourhood, and bringing sweeping changes to the public realm and streetscape pedestrian experience. The ultimate goal is to improve the quality of life at Yonge + St. Clair. In attracting ‘the types of tenants who can support an improved retail base’ Slate hopes to breathe new life into the neighbourhood’s 9-to-5 rhythm and take the energy up to 24-7. ‘My wife and I live in the area’, David Hopkins of restaurant consultants The Fifteen Group tells National Post, ‘and we certainly don’t go to Yonge and St. Clair if we’re looking for somewhere to eat.’ This echoes a familiar sentiment. But through the reinvention of the 4 corners Slate is confident they can change that tune. And the newly proposed patio and restaurant space at 2 St. Clair West is a leap in the right direction. Countless neighbourhoods across the city have successfully reinvented themselves with much more than a tired public sentiment working against them. Yonge + St. Clair is in a unique position to capitalize. Lucas is adamant that ‘[t]his is not a flipping strategy… It’s an own forever strategy.’ And with enough property to effectively act as their own business improvement area Slate not only has the passion but the means to make good on their promise.	cc/2019-30/en_head_0044.json.gz/line3416
__label__wiki	0.527691	0.527691	DC Comics Batman Pop Up Backpack A handy superhero power to have when you need it – this Batman Pop-Up Backpack can be folded away into a self-contained Batman logo pouch when not in use, but is full size when opened up. Featuring an iconic Batman design, including classic comic strip images and logos, this Pop-Up Backpack is a perfect Batman style hidden utility to pull out when needed most. Batman is the legendary comic book hero from DC Comics. First appearing in Detective Comics in 1939, he has since gone on to become a global icon of popular culture, featuring in blockbuster movies such as Batman Begins, The Dark Knight, and Batman v Superman: Dawn of Justice, as well as countless TV versions, graphic novels, and video games like Arkham Knight. DC Comics is responsible for creating many of the best loved characters in pop culture history, including Batman, Superman, and Wonder Woman among others, as well as popular crime fighting teams such as The Justice League and Suicide Squad. A great gift for fans of the comic books, films and TV series, the Batman Pop-Up Backpack is an officially licensed DC Comics product.	cc/2019-30/en_head_0044.json.gz/line3417
__label__cc	0.576859	0.423141	One Last Christmas Gift December 25, 2017 by zero dinh in Christmas, Music and tagged Music \| 1 Comment I hope everyone had a nice Christmas. This is our last Christmas together on the ZW Blog, and there’s one last present under that tree for everyone! It’s the ZW soundtrack! Newly released just in time for Christmas (and the end of the blog)! It has 20 tracks and a secret song at the end! Track 1: The Monster– Eminem ft. Rihanna Track 2: Zero– Yeah Yeah Yeahs Track 3: Three Is The Magic Number– Blind Melon Track 4: Cunt – Kat McSnatch Track 5: Fuck You– Lily Allen Track 6: Restless Heart Syndrome– Green Day Track 7: My Name– Xzibit Feat, Eminem & Nate Dogg Track 8: Richard– Obie Trice Feat. Eminem Track 9: Brand New Key– Melanie Track 10: Relief– Sixx A.M. Track 11: California Kids– Weezer Track 12: Making Friends– Lagwagon Track 13: Rhyme Or Reason– Eminem Track 14: Wreak Havoc– Skylar Grey Track 15: The Bitter Pill– Warrant Track 16: What You Give– Tesla Track 17: Sloth’s Revenge– Dirty Heads Track 18: Heathens– 21 Pilots Track 19: All Bad Things– Motley Crue Track 20: Encore– Eminem Frat. Dr. Dre. & 50 Cent 3 Of The Best Albums Of 2016 December 22, 2016 by zero dinh in California, Music and tagged Blink 182, California, Green Day, Offspring, Revolution Radio, Sixx A.M., Weezer, White Album \| 6 Comments #Three First let me say, the title reads “3 Of The Best” not “The 3 Best”. So don’t give me any grief about there being better albums last year, maybe there were. I’ve yet to hear the new Sixx A.M. album (hoping to get it for Christmas) and I’m sure that will be at the top of my list. Also not everyone has the same taste in music… Dorothy obviously hates my taste in music… too angry for her. Still these 3 albums will be hard to beat in my opinion. So a little while back Sassy (for new readers: that’s my wife), came home and told me she got me a present. Before she had went out I had mentioned I needed to head to the record store because there several new albums out I needed to pick up, so I knew she got me an album. I sat there all excited as she reached in to a bag and pulled out the new Blink 182 CD. Fuck yea! I had really been waiting for that one. Then she said, “Wait, there’s more”. And she reached in and pulled out the new Green Day CD. Sweet! Another one I wanted! But she wasn’t done… she reached in and pulled out a third CD (my baby knows me so well), Weezer! Oh hell yea! 3 new CDs from 3 of my favorite bands. I was set! And can I tell you they did not disappoint. All three albums kick ass and show just why these 3 bands are 3 of the best still out there making albums. Since I have been listening to them over and over for the past few months I thought I’d go over them all for all of you. You’re welcome. LOL. So as I have said before, “The Music Album” is one of the many things that has been screwed up by the internet. Music is now made in single tracks to be collected off YouTube or other such places. Don’t get me wrong, radio always made sure the single was an important part of music. Many people bought albums for just one song they heard off the radio and I can tell you from experience of working at record stores in the 90’s that lots of people went looking for the “cassette single” never realizing how good the whole album was and therefore missing out on great songs. A good example of this is Offspring’s “Come Out And Play”. Everyone came in looking for that single not realizing how great an album “Smash” was/is. I was always a whole album kind of guy. I liked (still like) to put the album on, listen to it from beginning to end and see where the artist can take me. But the internet killed the album all together. Now there aren’t many albums being made that are worth buying… the single has found its true home on the internet. songs are made for the download numbers… and albums on a whole seem to be less important… or not important at all. And this is why I was so glad these 3 albums were ALBUMS. I can put them on and off I went. It definitely helped that California was a running theme on a few of them. You know I love my California. Which brings us to the first album, Blink 182: California: I heard the first single, “She’s Out Of Her Mind” on the radio. And I like it, but it sounded like a younger Blink 182, and I was afraid the album would try to hard to be like they are still a high school pop-punk band instead of the growing sound that they had matured into with each album. Plus I felt the song was missing Tom. I think that was my worst fear, that without Tom it just wouldn’t sound like Blink 182. I mean other than Boxcar Racer, I wasnt a big fan of their solo stuff. I like Mark and Tom harmonizing together with Travis pounding away on the drums. The 3 of them together made the sound of Blink 182 (I know Travis wasn’t there for the early albums, and I do love those albums too maybe even more… but for argument’s sake and the sake of this blog, the 3 of them make the sound). I was worried for nothing, the album works on all aspects for me. It sounds great, lyrics are good, and the concept well, California… it don’t get any better. Here;s a track list. The whole album is great, but I put 3 stars next to my favorite tracks: 1.* “Cynical” 1:55 2. “Bored to Death“ 3:55 3. “She’s Out of Her Mind“ 2:42 4.* “Los Angeles” 3:03 5. “Sober” Hoppus Feldmann 6. “Built This Pool” 0:16 7.* “No Future” 3:45 8.* “Home Is Such a Lonely Place” David Hodges 9.* “Kings of the Weekend” 10. “Teenage Satellites” 11. “Left Alone” 3:09 12.* “Rabbit Hole” 2:35 13.* “San Diego” 14. “The Only Thing That Matters” 1:57 15.* “California” Martin Johnson 16. “Brohemian Rhapsody” 0:30 With song titles like “Los Angles”, “San Diego”. and “California” how can you not love it? I will admit, there are quite a few songs where I wish I could have heard with Tom, but even the single grew on me. In all honesty this album is the best to expect from Blink 182 after all these years, meaning it stands up with all the rest. With or without Tom. I’m gonna play one song from each album (so we end up with 3 songs… duh). The one I chose from this album needs no explanation: Now on to Green Day’s Revolution Radio: 1. “Somewhere Now” 4:08 2. “Bang Bang“ 3:25 3. * “Revolution Radio” 3:00 4.* “Say Goodbye” 3:39 5.* “Outlaws” 5:02 6. “Bouncing Off the Wall” 2:40 7.* “Still Breathing“ 3:44 8.* “Youngblood” 2:32 9. “Too Dumb to Die” 3:23 10. “Troubled Times” 3:04 11.* “Forever Now” I. “I’m Freaking Out” II. “A Better Way to Die” III. “Somewhere (Reprise)” 12. “Ordinary World” (lyrics and music by Billie Joe Armstrong) 3:00 If you like Green Day you should like this album. It’s a little like the rock opera’s American Idiot and 21st Century Breakdown. Though I found it more like their last 3 albums ¡Uno! , ¡Dos!, and ¡Tré! Point is, it’s all Green Day. The other 2 albums were easier to choose what songs to play. This one I had I debated on. I decided on the song that sounded the least like Green Day. I kept finding myself coming back to it. I get a lot from this song. I hope some of you will as well: I saved the best for last. The new self titled Weezer album. Weezer had made 3 other self titled albums. Each one would become known by the color of the album cover. Blue, Green, and Red. Each of these are fucking awesome. Blue and Red are masterpieces and 2 of my favorite albums. The color of this album (the band on the beach, so you know where this is going) is mostly white, therefore earning the name White Album. Which just happens to be the name of one of the biggest masterpieces of all time.So this album had a lot to live up to: My favorite place! Let’s look at the track list: 1.* “California Kids” Rivers Cuomo, Dan Wilson 3:25 2.* “Wind in Our Sail” Cuomo, Scott Chesak, Ryan Spraker 2:53 3.* “Thank God for Girls“ Cuomo, Alex Goose, Michael Balzer, Alex Balzer, Bill Petti 3:30 4.* “(Girl We Got A) Good Thing” Cuomo 3:25 5.* “Do You Wanna Get High?“ Cuomo 3:27 6.* “King of the World“ Cuomo, Jarrad Kritzstein 3:24 7.* “Summer Elaine and Drunk Dori” Cuomo 3:25 8.* “L.A. Girlz” Cuomo, Brian Bell, Luther Russell 3:29 9.* “Jacked Up” Cuomo, Jonathan Coffer, Hugh Pescod 2:53 10.*** “Endless Bummer” Cuomo, Bell, Russell 4:14 I’m not saying this album should be compared to the other White Album. I’m not even saying it’s the best Weezer album (though it’s up there). All I’m saying is as soon as I heard that first song, I was hooked. And the rest of the album took me on a journey that only the best albums can do. This album made me want to write this post. Before I leave you with that opening track, let me just say, I was once a “California Kid”and this song gets put on repeat a lot! I’ll always be a Californian, and I know Vegas isn’t that far from my true home… but sometimes the desert seems like the furthest place from those California beaches I grew up on. As for the kid thing… I know I’m a long way from there, but I’ll always be a kid at heart. At the end of the day (have I ever mentioned how much I hate when people say that) if we all find ourselves on a sinking ship… head to California… I’ll meet you at the beach… I’ll show ya the sunshine. AUTHORS NOTE: this Weezer video is actually the third of a somewhat trilogy. To see the other 2 videos, go to the ZW Facebook. https://www.facebook.com/zerosworld/ #Three And Music December 21, 2016 by zero dinh in 3, Music and tagged 3, 3 Strange Days, Britney Spears, Music, School Of Fish, Sea Hags, three, Threes A Charm \| Leave a comment So one idea I had for #Three was to make a group of posts called “3 Songs“. where I would post 3 songs that all had something to do with each other. The first post was called “3 Songs”. But although I had the 3 songs pulled aside I didn’t write a post. These are the 3 songs: See how they all have the number 3 in the titles? 3 Songs. The next post would have been called something like “3 Old Songs” and I would have posted 3 songs about getting old. Or maybe “3 Rock Songs” where I’d post 3 songs about rocks. Or something like that. You get it. Doesn’t matter, I never got to it and there just isn’t enough time left in this third year to get to it. Too bad ’cause I had lots of ideas for it, back when I first thought of doing it (the blog was still in year 2 so I had to wait) I would hear a song and say, that would be a good song for 3 songs and see what other 2 songs I could connect it to. It was fun that never got to the blog. Sorry about that. I hope you liked the 3 songs I had picked out for the post that never was. The first one, “Three’s A Charm”, is from a band called Sea Hags. They are what some call glam metal or a hair band. I thought they were cool but they were kind of late to the party and missed out on the late ’80s uproar for the excess of sex, drugs, and hairspray. Still if you find this song cool like I did, I would suggest checking out the rest of the self-titled album. You might dig it. The second is a little more well know, School of Fish’s “3 Strange Days”. I have always liked this song and in fact it inspired a very strange dream I had once, that took place over 3 days ( I wasn’t asleep for 3 days, but 3 days passed in the dream). The third song is Britney Spears, 3. I think it’s self-explanatory why I picked it (it’s called 3). So there ya go. The real post would have probably been a little longer and gone more into each song, plus it would have been followed with other post, each with 3 new songs somehow connected. It might have been fun. Oh well. I didn’t bring this all up for nothing though. For one I had these 3 videos sitting in an unnamed, unfinished post and I wanted to delete it or post it. Plus I wanted to lead into one last #Three post. It’s also about music… Dying Heroes January 17, 2016 by zero dinh in David Bowie, Howard Stern, Music, Nikki Sixx and tagged 58, All My Heros Are Dead, David Bowie, Diet For A New America, Howard Stern, Lemmy Kilmister, Natalie Cole, Nikki Sixx, Ziggy Stardust And The Spiders From Mars \| 5 Comments The track above comes from a Nikki Sixx solo project called 58. The song is called All My Heroes Are Dead Now. The album is called Diet For A New America. It came out in 2000. Don’t feel bad if you never heard of it, most people haven’t, which is too bad, because it is quite a remarkable album. Different from most of the stuff out 16 years ago, even different from most of the stuff out today. The album was way ahead of its time, and still is in my opinion. Please check it out, you won’t be disappointed. When I first heard this song back at the turn of the century, the impact of what it was saying hit deep. It wasn’t a new concept of course. People have been singing about losing their heroes long before I came to be. It’s a part of life that can’t be skipped unless you leave early or choose not to have heroes. Both ideas are very sad to me. I have been lucky enough to both to have lived a little while and to have many, many heroes. I’ve use the word lucky a lot lately… I definitely feel I have lived a lucky life… I also feel lucky is just another word for blessed. And in this world of contradictions, being blessed is also being cursed. I know, that doesn’t sound right, but it’s true. Back when I first heard the song I was quite a bit younger than I am today, (duh, 16 years younger) and it made me think of my lost heroes like John Lennon, Sid Vicious, and Kurt Cobain. But to be honest, other than Kurt most of my dead heroes were dead before they were heroes and Kurt was a quick flash, in and out, still very influential to me and his death was a shock and left its hole, but again it was all so quick. Also, with these heroes (John, Sid, and Kurt) their deaths were part of the whole romance, part of the story, part of the hero. Sorry words can’t help me get to what I’m trying to say, but I know most of you get it. I never want to claim to know what a writer of a song is trying to say, but I definitely don’t mind talking about what the songs say to me. And in this song, I knew that there might come a day when I would feel all my heroes were gone, the blessings of the curse. I turned 45 the other day. I know most who read here are a little older than me and hate when I talk about how OLD I’m getting. I know, I know, I’m still really young… but I can’t help it, I feel my age. If it’s any consolation, as I’ve pointed out before, I’ve lived a very excessive life, and therefore I don’t just feel my age, but the life I lived as well, and damn it, I feel old. Regardless, 16 years later (older), and the first of my heroes (the ones who have been there from the beginning and make you feel like they will be there forever) is dead. And I won’t lie, I’m not ready for it. And I’m not taking the news of David Bowie’s death well. Even after a week it’s still sitting very heavy on all my thoughts. I’ve been playing all my Bowie records all week remembering all the years his music was there for me, after all it’s been there my whole life. I really haven’t been doing too much else this week. Haven’t checked any social media or the blogs (and I see I’ve missed a few things, but we shall get to ALL of that in good time). I plan to write a more detailed memorial for David Bowie soon, when I can deal with this loss clearer. For now I’ll end this post with how last weekend crashed into my life, like a diesel truck hauling nitro glycerine. I had spent Saturday January 9th, 2016 listening to Howard Stern and catching up. I hadn’t listened in a few months. I was devastated hearing of Riley Martin passing away recently: Riley Martin Dead: ‘Howard Stern Show’ Regular & Alien Expert Dies At 69 Damn, I loved Riley Martin. His death saddened me even if I wasn’t too surprised by the news. Howard had often said Riley did not seem to be doing well, and since there had been a couple other Howard Stern show deaths this year, mentioned in this earlier post: https://zerodinh.wordpress.com/2015/03/15/howard-stern-vs-madonna/ I had thought that a third death was imminent, and that it would probably be Riley. So I was not surprised, but still very sad from the news. Later that night I thought about making a post about the things discussed on Howard Stern that day and thinking about Riley. And then I thought about how Natalie Cole and Lemmy Kilmister from Motorhead had both recently died. The 58 song came back to me. These were heroes to people, lots of people. Their deaths were more than just deaths, they were the loss of heroes. Now some of you may doubt this part, but this is what happened and you can check television listings for that Saturday night if you don’t believe me. I was sitting there thinking about dying heroes and the 58 song and a David Bowie documentary came on the T.V. It was called David Bowie: 5 Years. I had never seen it before, and it was so good and brought me to some great memories I have that go along with all those Bowie songs discussed in the documentary. It was cheering me up and then the drastic thought came to me. The song tells the truth, my heroes will all be dead one day. Not David Bowie though, I told myself as “Diamond Dogs” played on my T.V. I couldn’t even let the thought form completely. I still hadn’t seen a David Bowie show, surely David wasn’t going anywhere till I saw him live. But something dark nudged at my soul. Still I would not let the thought finish in my head. It was just too much to wrap my head around. Until the next day when I was forced to finish the thought. I had just come to the blog and was deciding if I would write about Howard Stern or the many other things in my head begging to be worked into posts, the television was on, news (as usual) and they announced that David Bowie had died. I just looked at the screen at first not believing it, it was a trick of some kind. I looked at my wife who immediately teared up, she was seeing what I was seeing. I cried out. “No…” My wife said that she had woken up last night saw I was watching something about David Bowie and she had thought that she would really like to see him live again (Sassy was lucky (blessed) enough to see David Bowie live with Nine Inch Nails), I told her I had been thinking how great it would be for us to go see him live together. Then we both had tears running down our faces. I turned off the computer, no longer in the mood to write a post and put on my copy of Ziggy Stardust And The Spiders From Mars. And that’s where I’ve been the whole week, lost in my Bowie records, felling my age, mourning the loss of my hero. Motley In Vegas December 23, 2015 by zero dinh in Concerts, Motley Crue, Music, Zero's World and tagged Aladdin Casino, Generation Swine, Las Vegas, Mick Mars, Motley Crue, Nikki Sixx, Tommy Lee, Vince Neil \| 6 Comments So, we moved to Las Vegas, had a 4th child (another boy, so 2 girls, 2 boys), and then everything changed. I won’t get into the details or place too much blame, but my wife and I had outgrown each other and decided to get divorced. As most of you reading know, I got custody of the kids but I didn’t raise them alone, because I met Sassy (she worked with me at Tower Records). Sassy was an angel sent straight from heaven, my soul mate, best friend, and with out her I don’t know what would have happened, an angel sent straight from heaven. And guess what… Vince got back with Motley Crue! Yep, Vince rejoined the band and the result was Generation Swine: In my list of favorite Motley albums, this one comes in second, right after the first album Too Fast For Love. As usual, my first taste of it was a video: What a freaking cool video! What a freaking cool song! And the fact that Hustler Magazine creator Larry Flint being in the video was a lot like when they did the Clockwork Orange thing. No need to elaborate there, I don’t think. For the first time, I had the internet to see what people thought of the new album, and most hated it. They said it was one of the worst. Really? Fucking haters. This album was way ahead of its time. And once again, people did not like Motley changing with the times. Well. People other than me. I love this album! One listen to the updated Shout At The Devil and you knew Crue was back and they were playing for keeps: So when they came to Vegas, I was there. This time I would be taking a lot of people for their first Motley concert. My future wife Sassy had never seen them, that needed to be fixed. My sister was in town visiting, so I got her a ticket for her first Motley experience. Two of Sassy’s close friends also came with us to see Motley Crue for the first time. This would also be the first Motley Crue show for one of my kids. Well, first one that wasn’t in utero. My oldest who was now 10 years old came along for her first concert and just like mine, it was Motley Crue! So me, Sassy, my daughter, my sister, and two good friends all in August of 1997 all went to see if Motley still had it. I should point out that they were playing at the Aladdin Casino which was being closed down and remodeled. So this was the last show to be played there before it shut down: And let me tell you, it was one of the wildest shows I have ever seen. First off Live Wire definitely returned to the best song of the night but it was joined by a couple new ones. Right before Vince had left the Crue, they had released a greatest hits album to celebrate 10 years together and on it was a remake of Sex Pistol’s Anarchy in The U.K. and a new song called Primal Scream. Many consider Primal Scream their favorite Motley song and with good reason, the song is the shit! It came out, as I said right before Vince was gone, so I had only heard it live with John Corabi, and I have to admit it just wasn’t right. But now with Vince back it could become what it was meant to be live. Which is awesome! Yes. that song is the shit! Together with the Anarchy cover, the show we saw that night was very punk rock. My roots, and I fucking loved it! Towards the end of the show the band said since it was the last night of the theater being opened that maybe some destruction was needed. They told everyone to come down to the front. We were pretty far back, and it was my 10-year-old daughters first concert so we stayed back. Well most of us did. Sassy’s friends wanted to head down and I said to them, “What are you waiting for?” They went down and we watched as most of the theater crowed to the front of the stage and begin to rip out chairs, passing them aside making a standing room only floor where it was all seated theater just moments before. It was madness and the boys in the band were encouraging all of it! It didn’t stop after the show either. That place was out of control, everyone trying to tear the place down. When I came out of the bathroom two girl were dragging a pay phone across the floor. At closer look, I realized it was Sassy and her friend. A security guard quickly came up and told them to leave it alone. And just for the record someone else had pulled it from the wall, Sassy and her friend just started dragging it after it was on the ground. There were cops lined up at the front ready to come in if needed, but over all everyone kept their cool, no one was hurt and no real riot broke out. Just a side note here… a few years later Motley Crue returned to Vegas and did find themselves in trouble for inciting a riot: http://www.mtv.com/news/1432369/nikki-sixx-and-crue-crew-arrested-in-las-vegas/ Unfortunately I was not at that show, and I want tot stress, that all though the Aladdin show got a little out of hand, my daughter was never in danger. It was a fun night and EVERYONE had the time of their lives. I still have a “no smoking” sign that I took from the theater hanging in my bathroom. And all those who came with me to the show now understood what a big deal a Motley Crue show was. Live Without Vince December 23, 2015 by zero dinh in Motley Crue, Music, Zero's World and tagged Covina, John Corabi, Lake Elsinore, Mick Mars, Motley Crue, Nikki Sixx, Palladium, The Video Studio, Tommy Lee, Tower Records, Vince Neil \| Leave a comment Exactly wo years after I sat in the hospital holding my daughter after one of the best concerts I would ever see in my life, tragedy struck February 14, 1992 Vince Neil was kicked out of Motley Crue. I was devastated. I was still working as a manager of a video store in Covina, when I heard Vince Neil on a local radio station (Pirate Radio). I was at work and a customer came in while I was listening to it and a tear fell from my eye. The customer kidded me about it, but only a little, my customers knew how big of a Motley fan I was. In fact working at a video store in Covina meant a lot of my customers went to school with Vince and/or Tommy. And in the 3 years I spent at The Video Studio in Covina, California, I met all sorts of people who had opinions of Vince Neil and Tommy Lee, I met ex girlfriends, class mates, and even Tommy Lee’s sister and mother once. My brother actually went to school with Vince Neil’s daughter. Most people didn’t have nice things about Vince, a lot of guys claiming they kicked his ass, blah blah, blah. Everyone loved Tommy though, a classmate of his told me he was always banging on the desk like drums and saying he was gonna be a rock star one day. So yes, my customers knew I was a Crue Junkie and they fed me well. One of Vince Neil’s ex girlfriends sold me a bunch of stuff from those early days including an autographed copy of Leathur Records version of Too Fast For Love. For those who aren’t die-hard fans I’ll explain. Motley Crue couldn’t get signed at first, so they started their own record label called Lethur Records and released an early version of Too Fast For Love. The album sold over like 20, 000 copies and Electra Records snatched them up, dropped the song Stick To Your Guns, and touched up the rest, and released it under Electra. The copy I have is even before what The Crue sold. The one I have is an original before art work was changed (Vince Neil didn’t like the way his hair looked in it, from what the ex girlfriend says. And in the one I have the hair is real puffy and funny looking against the white background of the album. The ex girlfriend told me Nikki called him tampon head, that tells you what it looks like. So they cropped Vince’s hair in the copies they sold and on the version Electra put out.) My copy was Vince’s personal copy from what I’m told. And that was just some of the cool things I got from Vince’s ex. Thanks to her being a member at the video store I worked at, my Motley collection is huge! So there I was at work, tears running down my cheek while Vince Neil announced on the radio that he was no longer part of Motley Crue. Yes, I was devastated! Nikki and the rest of the band would later come out and say Vince quit the band, something still disputed to this day. Regardless the result was Vince going solo and Motley getting a new lead singer. There were lots of rumors about who might replace Vince but the guy who got the gig was John Corabi, lead singer of a band called The Scream who had a small hit not to long before he left his band and joined up with The Crue: I was desperately waiting to see and hear what this would do to Motley, and like usual it came from a video. I was visiting my dad when this video came on MTV: I was ecstatic. It was like when I first heard Dr. Feelgood or the first time I saw the Too Young To Fall In Love Video. It was so new, so different, and yet it was Motley Crue. And the video has major “Clockwork Orange” references, easily one of my top 3 favorite movies. I couldn’t wait for the new album to come out. Since the last time I had seen them live we had another child. Our first boy. We had moved to Oakland for a while, back to Lake Elsinore before returning to Covina. I was working at Tower Records in West Covina (The Video Studio sadly closed down) when the new album would come out, simply titled Motley Crue. Working there I got to hear what people thought and most people didn’t like it. I don’t think people were ready for it, but to this day it is still one of my favorites. With songs like Misunderstood, Drift Away, and Loveshine: This was a more mature Motley Crue and maybe some of the fans weren’t ready for it (like they weren’t ready for Theater of Pain, or how they wouldn’t be ready for Generation Swine in the near future, but we’ll get to that in the next post). I get people don’t like change, but that’s one of the reasons I stuck with the Crue so long, they grew with me… not that there aren’t some great rockers on the album: The album was great, fuck all the haters, and when I saw tickets were going on sale for the “Anywhere There’s Electricity” show I was there to get them. Since there was a Ticket Master right in Tower Records I went while I was at work and got 4 tickets for August, 1994 at the Palladium. I was going to see the Crue for the third time! Well most of them. Three of them and a new guy. This would be the only time I see them live without all 4 of the original Crue. My then wife of course went to the show, it was only fair that she get to see the band without the contractions. I took my brother Michael, I believe some of you know him, (it was his very first concert) and my then wife’s brother (is that a confusing sentence? I took my ex-wife (though she was my wife at the time), her brother, and my brother. This was just a few days before I would move to Las Vegas and it was quite different then the shows I was used to. I was used to big arena shows, Palladium is tiny. Which for me made the night very personal. Highlights: Nikki Sixx doing a bass solo and jumped into the crowd, body surfing while playing his bass. The new album was way heavier on the bass than the previous albums and Nikki’s bass was like the heartbeat of the show. I also crowd surfed. It was my first time doing it and it was fucking awesome. If you have never been floating on top of the crowd as your favorite band rocks out, you haven’t lived. When you come down from the crowd you end up in that area between the crowd and the stage where a big security guard rushes you out and back into the show. One of the times I came down into this area I found myself staring right up at Nikki and he was looking at me. He held out his hand reaching down at me from the stage, I held mine out and shook his hand, mumbling “I love you”. I know, what a corny fruitcake. But I was starstruck. And at that moment I was a teen age girl, I know it and accept it. Tommy’s extravagant drum solo was stripped way down, but that doesn’t mean it wasn’t bad ass! Fit into the pounding solo was some of Tommy’s song Planet Boom: The song is from the EP Quarternary, a special CD you could order where each member of Motley did their own song. I have a couple of copies of it including the Japanese import with several extra songs. What a “fan boy”. Although the drum solo was simple, it hit the mark. It was the first time, and maybe the only time, I saw people form a mosh pit to a drum solo. I should point out my brother had a great time at his first concert, though my ex wife’s brother did not enjoy it as much. He said he had a hard time figuring out what songs were playing. He didn’t know the new stuff too well and the old stuff did sound different with John singing, but that’s what I liked about it. It was so different. My ex had a good time too, after all there was no one in her tummy banging to get out and enjoy the show. Though she did have a little one in her tummy. We didn’t know it at the time, but she was a few weeks pregnant with out fourth and last child together (next post). Well fuck my ex’s brother, the show was awesome! Though since it was so different, it was the only time Live Wire was not the song of the night. For me it wasn’t really one song but a group of them that stands out. Towards the end of the show, some couches were put out on stage and a bunch of people were picked from the audience and went up and sat in them. It was set up like a living room and the band did an acoustic session, with about 10 fans sitting around on stage with them. I wasn’t one of them, but I still enjoyed watching it. They did Home Sweet Home. a cover of The Beatles’ Revolution, Loveshine, and Don’t go Away Mad (Just Go Away). All acoustic. Definitely the highlight of the night for me. It was an end of an era for me. Shortly afterwards, I said good bye to Southern California where I had lived for most of my 23 years at that point and headed to the lights of Las Vegas. And by the time Motley would come back around life once again had changed drastically while staying quite the same. December 20, 2015 by zero dinh in Concerts, Motley Crue, Music and tagged Aerosmith, Allister Fiend, Coliseum, Faster Pussycat, Guns N Roses, Iron Maiden, Los Angeles, Mick Mars, Motley Crue, Nikki Sixx, Rolling Stones, Tommy Lee, Vince Neil \| 17 Comments By the time 1987 came around with Motley’s fourth album “Girls. Girls. Girls” A lot had changed in my life. A lot for just 2 short years at least. I had moved from Perris, California to live in Lake Elsinore, California with my dad (my mom and step dad were getting back together and it was for the best that I go live with my dad). And then not long after that I got my girlfriend pregnant and we were now living in our own studio apartment (with a Murphy bed that came right out of the wall like Tommy’s drum set from that first concert). The album came out and a concert followed. First the opening band was Whitesnake. But that didn’t last because David Coverdale is such an egomaniac, dick. Can you believe he was saying his band was bringing all the girls to the concert. Yea fuck him, lol. The next band to join the tour was Guns N Roses. You don’t know how bad I wanted to go to that show. But as I said my girlfriend was pregnant. And when the Crue rolled into town she was like 8 months pregnant. To make things worse my ex girlfriend, who had moved away the year before showed up with 2 tickets to the show and wanted to take me. There was no way I could leave my pregnant girlfriend and go to a concert with my ex girlfriend, no matter how bad I wanted to, there was just no way. So I missed that show and I missed Tommy’s drum solo where he went in a complete 360. Luckily the video for Wild Side captured it for me: Man, I can’t believe I missed that concert. The next time Motley came around wouldn’t be till 1990. My life had changed a lot again in those years and yet also things were very similar. I was now married with a daughter and living in Covina (which is where Motley Crue formed, by the way). I was working as a manager of a video store when tickets went on sale for the February 13th show at the Forum with opening band Faster Pussycat (another one of my favorite bands). February 13th was the day before our first wedding anniversary (yes, I married my first wife on Valentines Day, I don’t recommend it). I had to get tickets. The only thing was, just like last time Motley Crue was on tour, my then girlfriend, now wife, was pregnant again. But it didn’t seem to be a problem, she was due the week before. LOL. The newest Crue album had come out the year before and from the first time I heard the title track Dr. Feelgood, (which I had heard on the radio a few weeks before the album came out. We didn’t have an internet to chase down songs before the albums were out. So that first single was all you got to go by) I knew that album was going to be great. And it was, so yes, tickets had to be bought: I couldn’t wait to see Motley Crue for a second time. I had been to a few shows in between that first one in ’85 and this one in ’90, Iron Maiden, Guns n Roses with Aerosmith, in fact just a few months earlier I had won tickets to go see Guns n Roses with The Rolling Stones at the Los Angeles Coliseum. Yes, just a few months before this Motley Crue show I had gone and seen Guns n Roses open for The Rolling Stones. What a great show, but due to the fact I didn’t take my wife, then a few months pregnant, not my decision alone, but it was a bad one, sort of, I guess, lol. It caused lots of problems but that’s all you get about the Guns N Roses/Rolling Stones concert for now, no one here is ready for that story! Still because I didn’t take my wife to the Rolling Stones, because we didn’t see the Girls, Girls, Girls show, because the following day was our first wedding anniversary, you might be able to understand the decisions made that day February 13th, 1990. I remember waking up in a really great mood. Everyone else was already up (we had 2 roommates at the time and they were both in the kitchen with my wife, both roommates were female, not that it matters, but just thought I’d point that out, keep Dorothy on the right track when she tries to use it to fit in her craziness). I went to the kitchen to see how my wife was. The past few days had been spent questioning the upcoming show. She had not had the baby yet and was very, very pregnant, due any day. Everyone was smiling, which worried me, but she said she was felling fine. She said not to worry everything would be fine. Now I don’t want to sound like the worlds biggest dick here (you can go read many other posts to see that) but I was worried and had been for a few days. It had been obvious the baby was not coming soon enough for my wife to go to the show. That time had come and gone. In fact if she had gone in to labor before the show, I most likely wasn’t going either. I know what a thing to worry about, but it was Motley Crue! Well all that was past now anyways, the day was here and the only question was, did my wife feel up to going to the show. She said she was and my day got even brighter. Go ahead judge me, but again it was Motley Crue. Alright, I was still nervous, but as the song says “On With The Show”! I put all four Motley CDs in the CD changer and got ready for the show. Another thing that had changed, tapes to CDs… I know, neither one matter anymore. Technology is a bitch. So we got ready, kissed our daughter good-bye and headed for L.A. (about a 20 minute drive with out traffic). We had a bottle of champagne that we were saving for our first anniversary (which remember, was the following day) and once we got to the Forum’s parking lot, we opened it up and had a glass, toasting our anniversary (and Motley Crue). Into the show we went. I can’t tell you what it was like to be 9 months pregnant at a Motley Crue show, but I can say, I kept asking my wife how she was, and she kept replying she was fine. Faster Pussycat came on and were awesome! When the lights went down and the arena was filled with lighters (a practice long gone, replaced now by cell phones) and they did House Of Pain: Powerful… powerful! Pussycat was done and it was time for The Crue to take the stage. We were way at the back, not like the 8th roll I was in the first time, but I didn’t care I was here again, and I was ready! Green lasers took to the front of the stage creating images. First a pentagram, then the theatrical masks one smiling, the other with one a tear of blood, that quickly became a motorcycle. All along a booming voice was telling us about the trip we had made so far. But now it was time for the Doctor and with that Allister Fiend, the lovable werewolf mascot of Motley Crue appeared in the green laser show dressed as a Doctor… as the booming voice announced it was time to “come play with Doctor Feelgood” That was when the first set of pyro went off shaking my pregnant wife next to me. Again, I asked if she was alright, she yes, she was fine. And with that Motley raged into a loud a furious Kickstart My Heart! Tommy had started the drum beat (at first he was the only one on stage) then with another loud expostion the rest of the guys came flying out of the ground and onto the stage. Once again, I was in sensory overload. The set list went on like this: Rattlesnake Shake Too Young to Fall In Love Shout At The Devil Same Ol’ Situation Slice Of You Pie Enough to take me back to that first show, while plenty of new to make it a different experience. I definitely think the performance of Live Wire was once again, the song of the night. Get use to me saying that. Mick then did a guitar solo. It was a slide guitar where he broke into parts of Without You, a song from the new album they did not do that night. But it made its way into the solo, and Mick is a guitar god! Tommy’s drum solo was next, and if I thought his first one was cool, if I thought what he did on the Girl, Girls, Girls tour was incredible, I was in for a shock. Tommy started to beat on that kit like no one else can and as he did so his drum set began to rise into the sky, high into the sky. Once it had risen to the top of the arena he stopped bangin’ on the drum long enough to say this: “You know, people are always asking me how I’m gonna top my last drum solo on the “Girls” tour”, I’m paraphrasing, remember this was 25 years ago, “And they keep asking ‘what are you gonna do, how can you top it?’ and I tell them… this!” And with that his drum set started moving along a track across the top of the arena ceiling. As it moved from the front of the arena to the back, Tommy played the drum part of other bands, songs from Kiss, Van Halen, Queen, etc. All the great anthems and the crowd below him sang each song out for him. Once again, this was like nothing I had ever seen before and by the time he reached the back (right above where we sat) I was again up on the highest clouds. This was just too amazing, it had to be the coolest thing I had ever seen. Tommy stopped playing again and stood up leaning over the edge of his drum platform, hanging right there in front of all of us way at the back of this big arena. He leaned over, took a big breath, and said, “Now I’m back here with all of you with the good weed!” The place went crazy! He sat back down playing more drum beats from crowd favorites, everyone singing all the words as the drum set made its way across the sky, back to the front of the Forum. Once there he jumped from the set, falling towards the crowd below, only to bounce back up from an attached bungee cord. Again, the place went crazy. I looked at my wife and she to was enjoying the show. And as the rest of the songs played out she was singing along with everyone else in the place. The set list continued on: Looks That Kill Smokin’ In The Boys Room Now, although my wife kept saying she was fine, and seemed to be having a good time, I could tell that each pyro explosion had an effect on her, and there were lots of them. So I have to admit, I was relieved when the Elvis Presley cover started, I knew that would be the last song, so I turned to my wife and said, we should head out to get ahead of everyone. “That’s a good idea,” she said smiling but not quite genuinely, “I’m in labor.” We have to take a step back 3 years to when I was 16 and in the delivery room waiting for my first child to be born. We were at the hospital for about 24 hours before my daughter finally came. It was scary, I was a kid, and the experience was the most confusing, magical experience of my life. I was a little older but the moment my wife said those words, “I’m in labor” confusion and magic all over again. As we raced to are car, I questioned her, “are you serious?”, “why didn’t you say anything?” She didn’t really answer, she just gave me a look. “I’ve been in labor since I woke up, this morning.” I knew those smiles were suspicious. Everyone at my house knew but didn’t say anything, not wanting to ruin the show. Really? Really? Was I upset they didn’t tell me, or happy I got to go to the show? I’m still not gonna try to answer that question, but at the time I was still full of adrenalin from the show and my mind was racing. We got to the car. My wife explains the reason she suggested the champagne toast was because she knew it would slow down the labor. “How close are you?” I asked. “Close,” she said. Now let me once again take us back 3 years, to our first-born. My wife, then girlfriend, had though it was time many times before it actually was. We were at the hospital twice before they actually admitted her the 3rd time, and as I said, after that we were still in the hospital for a 24 hour period before she gave birth. Luckily I wasn’t thinking about any of this, my mind was just trying to come to grips with everything, I was in shock of some sort, but I sprang into action. As we drove out of the parking lot heading for the freeway, it began to rain. I looked over at my wife who was breathing heavily obviously going through a contraction. This was insane, I mean WTF?!? I got us from L.A. to Covina in record time even with the rain. Went straight to my mom’s house. We rushed in, my wife was very calm, so I started to think everything was not as serious as that drive home-made it out to be. But once inside my mom timed the contractions and they were under 10 minutes apart. and they were getting stronger. So right back into the car we went and headed for the hospital. Again I can’t stress enough how 3 years earlier everything to move so slowly, painfully slow at times. There was time to be scared, there was time to worry. Not this time. We got to the hospital, were admitted, and in the elevator ride up to a room it was decided to go straight to the delivery room. During the elevator ride we told the nurses where we had just came from, they thought it was great, it was the first of many times that the story would be told, and we were the talk of the hospital. Not just because of the Motley Crue show, but it was now like two in the morning, Valentines Day, our first wedding anniversary. My second child was born right after we got off that elevator and into the delivery room. the whole thing was such a blur. The feelings experienced that night are not easily put into words. I mean one moment I’m watching Motley Crue and the next I’m holding my daughter (yes, another girl). Beautiful and healthy and she had already been to her first concert. Motley Crue!	cc/2019-30/en_head_0044.json.gz/line3420
__label__wiki	0.711819	0.711819	PowerDB is software used for the collection and reporting of data from maintenance and inspection activities performed on equipment used in the generation, transmission, and distribution of electric power. The software includes interfaces for many common test instruments and allows for automated testing and data acquisition, as well as imports from various file formats. Result and summary reports can be easily generated. Three editions of PowerDB are available for PC use: · PowerDB Pro · PowerDB Advanced · PowerDB Lite PowerDB provides a simple and consistent user interface to many Megger instruments including the DELTA Series Power Factor Test Sets, 3-Phase TTR units, earth testers, 5 and 10kV insulation testers, and many more. A fourth edition, PowerDB Onboard, is software embedded directly in the controllers of several select instruments. Results are stored in the instrument memory and are fully compatible with the PC versions of the software. PowerDB has its roots in Optima Systems, a company started in 1994 by Bruce Buxkemper who had previously worked for Megger in Dallas as a software developer. Located in College Station, Texas and with strong connections to Texas A&M University, Optima Systems initially focused on developing automation systems and software for industry. In the late 1990s, the company won a contract from Megger to develop the company’s AVTS software, a powerful yet easy to use package that complements Megger protective relay test sets. By the turn of the century, Optima Systems was also hard at work on an important project of its own – the development of PowerDB, a new software system that would provide a common user interface and uniform results handling facilities across a wide range of power instruments. This groundbreaking concept generated widespread interest and PowerDB was launched in the USA to considerable acclaim in 2001. In 2005, Optima Systems was purchased by Megger, an arrangement that has made it possible for the PowerDB system to be sold and supported in markets worldwide, and also provided access to the resources needed for its continuing development. Following its purchase by Megger, Optima Systems became PowerDB Inc., a Megger subsidiary. From its early days as a one-man operation, PowerDB has now grown to employ a number of fulltime and part-time programmers. Its primary focus is on the PowerDB system, which is now available in a range of implementations including an on-board version designed for total integration with instruments. The company continues, however, to develop other innovative hardware and software solutions for industry. The following are the current job openings we have at PowerDB:	cc/2019-30/en_head_0044.json.gz/line3422
__label__wiki	0.935338	0.935338	4/28/73: Dark Side of the Moon Hits #1 posted by Kenny Young - Apr 28, 2018 Following its debut a month earlier, Pink Floyd's Abbey Road-made masterpiece reached the Top spot of the U.S. Album charts on this date in 1973. Despite the fact that only two singles were released "Money" and "Us and Them", respectively, sales soared for the band's eight studio album. Dark Side of the Moon would only stay at #1 for one week, but its legacy was just beginning. To date, the album has sold over 50-million copies worldwide and still holds the record by remaining on the Billboard charts for 741 weeks, or just over 14 years. "It felt like the whole band were working together. It was a creative time. We were all very open." -Richard Wright. For more on one of the most influential albums in music and recording history, here's David Gilmour: {"position1": {"artist": {"bio": "", "id": 165, "name": "Pink Floyd"}, "catalog_type": "artist", "description": "", "id": 165, "name": "Pink Floyd", "related": [{"bio": "", "id": 1807, "name": "Led Zeppelin"}, {"bio": "", "id": 2358, "name": "Black Sabbath"}, {"bio": "", "id": 58402, "name": "The Doors"}, {"bio": "", "id": 3800, "name": "The Who"}, {"bio": "", "id": 252, "name": "Deep Purple"}, {"bio": "", "id": 35147, "name": "Lynyrd Skynyrd"}, {"bio": "", "id": 4258, "name": "Queen"}], "tagged": true, "type": "catalog"}}	cc/2019-30/en_head_0044.json.gz/line3424
__label__wiki	0.624448	0.624448	In consultation with the Preservation New Jersey Board and with the Presbytery of New Brunswick (with whom Preservation New Jersey holds a 50 year lease for the building), the 1867 Sanctuary Committee is responsible for overseeing all aspects of the restoration and operation of the 1867 Sanctuary at Ewing. In addition to facilities operation and management, this work includes grant writing and management, financial oversight, hiring and oversight of consultants and contractors, fund raising, publicity and outreach, and planning, scheduling and supporting events and activities. Members of the 1867 Sanctuary Committee serve at no remuneration, completely and totally out of love and dedication to returning this historic landmark to use by and for the community. The 1867 Sanctuary Committee was formed in 2012 under the leadership of its first chair, the late David K. Knights, at that time also the President of Preservation New Jersey. David’s zeal, encouragement, dedication and direct experience in restoring historic properties set a high standard for the work of the 1867 Sanctuary Committee. David’s passing in September 2013 was a great loss to the 1867 Sanctuary Committee, to Preservation New Jersey, and to New Jersey’s historic preservation community in general. We endeavor to honor David’s memory by successfully maintaining this landmark he worked so hard to preserve and protect as a legacy. Another monumental loss to our committee was the sudden passing of Rebecca Lovett in September of 2016. Becky was also a passionate supporter of our mission, a dear friend to all of us, and tireless volunteer. Memorial funds given in her name are being used to create a welcoming place for visitors at the entrance to the Sanctuary, in celebration of her welcoming and loving ways. The 1867 Committee would not be in existence without the past help other former Preservation New Jersey staff – Ron Emrich, Stephanie Cherry-Farmer, Tiwanda White-Pinkston, and Janice Armstrong. We thank them for their very early guidance, support, and encouragement. The 1867 Sanctuary Committee, which is currently chaired by Helen Kull, who is also Secretary to the Board of Preservation New Jersey, consists of seven very active volunteers, all of whom have contributed, and continue to contribute substantially to this effort in many ways: •Barbara Brennfleck •Ruth Ann Gribbin •Kathleen Jordan •Robert Kull •Donald Lovett •Dale Perry Additionally, The Rev. Paul Rhebergen serves as the Committee Liaison to the Presbytery of New Brunswick; and Scot Pannepacker, President of the Board of Preservation New Jersey, serves as an ex officio member of the Committee. We also acknowledge past and current members of the Preservation New Jersey Board, particularly Michael Mills, John Hatch, Megan Thomas, Michael Margulies, Jack Abgott, and Michael Hanrahan for their past and current guidance and sharing of their experience and expertise. In addition to the 1867 Sanctuary Committee members, we also acknowledge and appreciate the work of the many volunteers who have played important roles in organizing, publicizing, and staffing the many activities and events associated with the 1867 Sanctuary over the years. Preservation New Jersey is grateful for their time, effort, and the care so freely and earnestly given toward the restoration and operation of this historic building that means so much to them and to their community. If you would like to join our committee, or just volunteer to help on a limited project basis, please see our Volunteer Opportunities page, or contact Helen at 1867sanctuary@preservationnj.org. Thank you!	cc/2019-30/en_head_0044.json.gz/line3426
__label__wiki	0.755453	0.755453	Social Network & Media Contacts NWW2A 1. Kompanie Großdeutschland Weapons & Tactics > Standard Infantry Weapons Small Unit Tacticts Field Kit ranks-awards Sedgfield July 2014 Cleethorpes "Operation Frying Pan" August 2013 Hull Veterans Weekend July 2013 Northallerton June 2013 Fort Paull May 2013 Rank/Award NWW2A 1./ Kompanie Heavy Weapons 8cm GrW34 Medium Mortar MG42 machine gun mounted on a Lafayette Tripod MG34 & MG42 machine guns Mounted Front and Rear of the Sd. Kfz 251 Halftrack Panzershrek 8cm Granatwerfer 34 (GrW-34) The 8cm GrW 34 (heavy grenade-launcher model 1934) was the standard German medium mortar. Of world war two. With a maximum range 2,400 metres, a very well trained crew could accurately launch twenty-five 3.5kg rounds per minute on to a target, though the rate of fire would normally be 15 to 25 round per minute. Compared to infantry guns the GwR 34 was light and portable. After being broken down into its three component parts of a smooth bore barrel, a bi pod and a base-plate it could be relatively easily transported by it crew of four. Designed and developed by Rheinmetall-Borsig AG the GrW34 was intended to fire conventional High-Explosive (HE) and smoke rounds but in reality the weapon proved much more versatile and was also able to fire illumination rounds, a rare and unique bouncing bomb, the 8cm Wurfgranate 39. This was an air-burst shell which didn't use a timed fuse. It employed a small charge that would detonate on impact throwing the un-exploded main part of the round back into the air, at the same time triggering a delayed detonation of the main ordinance so it would explode 5-10 feet off the ground. The GrW34 could could also fire any captured enemy ammunition fitting its calibre though with some loss of performance. MG42 in "heavy" role mounted on a Lafayette Tripod Maschinengewehr 42, or "machine gun 42" also known as the MG42, and sometimes incorrectly referred to as a Spandau, was a 7.9mm general purpose machine gun. Developed in Nazi Germany it entered service with the Wehrmacht in 1942 it supplemented, and to some degree replaced the MG 34 though both weapons were manufactured and used until the end of the war. A very reliable, simple and easy to operate weapon the MG 42 has one of the highest average rates of fire of any single-barreled man-portable machine gun: between 1,200 and 1,500 rpm, which results in a distinctive muzzle report giving rise to its nickname "Hitler's Buzzsaw" MG4 in "light "role with bi-pod mounted at the front Maschinengewehr 42, (MG42) This outstanding and versatile weapon operated in a number roles within the German army of World War two. When removed from it Lafayette tripod and fitted with a bi-pod at the front it became a Light Machine gun, weighing in at 11.6 kg in light role, with bi-pod, it was lighter than its predecessor the MG 34. The bi-pod was the same one used on the MG 34,and could be mounted to the front or the centre of the weapon depending on where it was being used. There were other automatic weapon designs with similar fire-power to the MG42 but the MG 42's belt-feed and quick-change barrel system gave it the advantage. The MG 42 has lived on beyond its Nazi past. It was adopted by a number of armed organizations after the war, and was both copied and built under licence. The MG 42 was the basis for the almost identical MG1, subsequently evolving into the MG1A3, followed by the MG 3 and it lent many design elements to the US M60. Panzerschreck the literal literal translation is "armour fright" or "tank fright".It was popularly known as Ofenrohr or "stove pipe" but was officially the Raketenpanzerbüchse "Rocket tank rifle" or RPzB. The weapon is an 88 mm reusable anti-tank rocket launcher developed during World War II, designed as a lightweight infantry anti-tank weapon. The Panzershreck was shoulder-launched weapon which fired a fin-stabilized rocket with a shaped charge warhead. Versions of the Panzerschreck rocket could penetrate over 200 mm of armour and one direct hit would usually destroy any Allied armoured vehicle. It was so effective that Panzershrecks with well-trained crews became the bane of Allied armoured units. Their answer was to try and add improvised protection to their vehicles. Its not unusual to see photographs of tanks with, sandbags, spare tracks or logs fastened to them but most of this makeshift protection only overworked the vehicle's engine, transmission, and suspension. Allied troops preferred to use captured Panzerschrecks over Bazookas against Axis armoured vehicles, but they also needed to capture the ammunition which presented the problem of a limited supply of warheads. The Panzershrecks success in combat caused the Bazooka to be completely redesigned at the close of World War II. A larger, 3.5 in (90 mm) model was adopted, the M20 Super Bazooka. Though bearing a superficial resemblance to the Panzerschreck, the M20 had greater effective range, penetrating capability and was nearly 20% lighter than than the Raketenpanzerbüchse	cc/2019-30/en_head_0044.json.gz/line3427
__label__cc	0.707204	0.292796	Home ---------- Participants .Location ..City of Leipzig ...After work ...Restaurant guide ...Sights > Participants > City of Leipzig Center of business and science. Meeting place for culture and music. Leipzig is a vibrant metropolis with a 1,000-year-long history in trade and exhibitions. The city is centrally located in Saxony in the heart of Europe and easily accessible. Leipzig is an important traffic and transportation hub in Germany and has one of the most modern exhibition centers in Europe. Leipzig achieved world fame in 1989 as the “city of heroes” with the peaceful revolution, which started in Leipzig. The city is rich in history and culture. World-class artistic highlights include the Gewandhausorchester, the Thomanerchor and the Neue Leipziger Schule with Neo Rauch. Great composers like Bach, Mendelssohn, and Wagner, and writers like Goethe and Schiller lived and worked here. Leipzig is also known as the city of books or city of culture and has even more faces. Leipzig’s economy is characterized by the automotive industry, environmental and energy technologies, medical technology and logistics. Renowned companies such as Porsche, BMW, DHL, and Amazon have settled in this business location. Leipzig enjoys an excellent reputation for research and education. Leipzig's research centres are among the world's top scientific institutions. It hosts three Max Planck Institutes, two Fraunhofer Institutes, the Helmholtz Association, among others. Leipzig University is the second-oldest university in Germany and Leipzig is also home to many more institutions of higher education. Come to Leipzig, and learn more about the home of Leipziger Messe and the special atmosphere of this city! © LTM-Schmidt © Waltraud Grubitzsch Back to location City of Leipzig \| links	cc/2019-30/en_head_0044.json.gz/line3428
__label__cc	0.50813	0.49187	Account Solutions \| 2 Tower House Askham Fields Lane, Askham Bryan, York, YO23 3NU 11 St. Michael Street, Malton, North Yorkshire, YO17 7LJ Te;: 01653 695426 What do we stand for? Partner profiles/key staff Management Accountancy Paralegal Services Employment Legislation 2020 May bank holiday will be moved to mark 75th anniversary of VE Day Source: Department for Business Enterprise and Regulatory Reform \| \| 19/06/2019 The government has announced that the date of next year’s early May bank holiday is to move from Monday, 4 May to Friday, 8 May to mark the 75th anniversary of VE Day. This is only the second time ever that the early May bank holiday has been moved – the first was in 1995 to mark the 50th anniversary of VE Day. There will be commemorative events taking place across the country over the three-day weekend to honour the sacrifice made by men and women during the Second World War. VE Day was first celebrated on 8 May 1945 when Allied Forces formally accepted Germany’s surrender. The early May bank holiday will move in England, Wales and Northern Ireland, where it is achieved by a Royal Proclamation made under the Banking and Financial Dealings Act 1971. Bank holidays are a devolved issue in Scotland. However, Scottish Ministers have also confirmed the change of date on the Scottish government’s website. With our newsletter, you automatically receive our latest news by e-mail and get access to the archive including advanced search options! Copyright © 2019 - Accountancy and Business Solutions \| Cookie Policy	cc/2019-30/en_head_0044.json.gz/line3431
__label__cc	0.632664	0.367336	Arlington Ridge Luxury Homes Richard McGuire: Arlington Ridge McEnearney Property Management NOVA StatPak Report We Are McEnearney Takoma Park, DC Real Estate Located east of the northernmost point in D.C., in the Northwest quadrant, Takoma, DC is a neighborhood that is often confused with its Maryland neighbor, Takoma Park. The boundary confusion can be tracked back to the neighborhood's founder, Benjamin F. Gilbert, who decided to ignore jurisdictional lines and expand the neighborhood over the D.C. – Maryland border. The community of Takoma sprawled over 100 acres and included a small portion of the B&O Railroad. Takoma residents were originally reliant on the B&O railroad to move goods and travel. Gilbert advertised Takoma as a neighborhood located above swampy Washington City, one that offered fresh air and clean water. This explains how Takoma received its name; Takoma originates from the Native American word meaning “high up, near heaven.” Today the neighborhood of Takoma surrounds the red line Metro station with older Victorian and Sears’s style homes with large yards to complement the architecture. Within this primarily residential neighborhood is also a commercial district that is a short walk from of the center of town. Takoma is an active neighborhood with plenty to do and several events throughout the year. Residents enjoy Takoma Park Day, the Annual Takoma Antique and Classic Car Show and the Takoma Park Street Festival. Residents also have a weekly farmers’ market for fresh local food, and have access to the Takoma Aquatic Center for recreational activities. Takoma is also home to several restaurants, including the popular Roscoe’s Neapolitan Pizzeria, which almost everyone in Takoma knows is named after a rooster who once roamed the streets. Takoma’s primary form of public transportation is its red line Takoma Metro station. It also has frequent bus access if you are not looking for Metro service. Ronald Reagan National Airport: < 10 miles Washington-Dulles International Airport: < 30 miles Baltimore-Washington International Airport: < 35 miles View all Takoma Park Listings SEARCH FOR LISTINGS IN TAKOMA PARK Property Type Any Residential Land and Lot Multi-Family No Min $100,000 $125,000 $150,000 $175,000 $200,000 $225,000 $250,000 $275,000 $300,000 $325,000 $350,000 $375,000 $400,000 $425,000 $450,000 $475,000 $500,000 $550,000 $600,000 $650,000 $700,000 $750,000 $800,000 $850,000 $900,000 $950,000 $1,000,000 $1,250,000 $1,500,000 $1,750,000 $2,000,000 $2,250,000 $2,500,000 $2,750,000 $3,000,000 Max_Price No Max $100,000 $125,000 $150,000 $175,000 $200,000 $225,000 $250,000 $275,000 $300,000 $325,000 $350,000 $375,000 $400,000 $425,000 $450,000 $475,000 $500,000 $550,000 $600,000 $650,000 $700,000 $750,000 $800,000 $850,000 $900,000 $950,000 $1,000,000 $1,250,000 $1,500,000 $1,750,000 $2,000,000 $2,250,000 $2,500,000 $2,750,000 $3,000,000 7054 EASTERN AVENUE NW #310 Listed 07/10/2019 \| Pending There are no recently reduced properties in the last 7 days. There are no open houses. Map View tab	cc/2019-30/en_head_0044.json.gz/line3442
__label__wiki	0.645825	0.645825	If the only prayer you ever say in your entire life is thank you, it will be enough. - Meister Eckhart Jai Hindley wins stage four and moves into the race lead at the Tour of Fuzhou We're not following the Tour of Fuzhou, but I thought I'd share this update from the Mitchelton-Scott team: Giro d’Italia U23 stage winner Jai Hindley got everything right on stage four of the Tour of Fuzhou in China, taking the Queen stage win and moving into the race leaders yellow jersey with one more day of racing to come. The hardest day of this year’s race covered 130 kilometres with a first and second category climb forming the ascent to the finish line and also the platform for a GC battle. Mitchelton-SCOTT were prepared for the splits and with Hindley in fifth overall at the start of the day the Chinese/Australian outfit kept their leader well positioned as the race hit the climbs. As the selection formed with seven kilometres to go and on his preferred terrain Hindley looked strong and as the group whittled down to three it was Hindley who convincingly came out on top. “It was super nice to win today,” said Hindley. “It feels good to be able to give something back to the team that has given me so much support over the past couple of years. On tomorrow’s final stage we will do everything we can as a team to defend the jersey and the race lead.” Not only did Hindley move into the race lead, but Liu Jiankun also climbed the overall ranking into 16th place and maintains his position as the highest placed Chinese rider in the race. “I am really happy for the guys to get this result today,” said sport director Dave Sanders. “We have had some bad luck with crashes and sickness throughout the Asia Tour and it has cost us some potential results, but the guys have not stopped trying and they deserved to be up there today.” “The field kept splitting as they went up the final climb, it was pretty steep in places and over a tough road and that suited us. Jai rode really well and as it got down to first three riders, then two he looked confident and took the sprint convincingly. “It won't be easy tomorrow, it will be a challenging race around Yong Tai over some fast circuits, but we will do our best to defend the jersey and we are motivated for the challenge.” Tour of Fuzhou stage four results: 1. Jai Hindley (Mitchelton-SCOTT) 03:26:25 2. Fung Ka Hoo (Hong-Kong) ST 3. Stanislau Bazhkou (Minsk-Cycling-Club) +0:21 General classification after stage four: 2. Fung Ka Hoo (Hong-Kong) +0:04 3. Stanislau Bazhkou (Minsk-Cycling-Club) +0.15 Max Schachmann: The road to recovery and dreaming of a Grand Tour start Team Quick-Step Floors posted this: We caught up with our neo-pro Max Schachmann on his first season with Quick-Step Floors and the road to recovery after his Tour de Pologne crash: Cheers, everyone! Long time no see! How are you? How are you handling the off-season? Bet you're counting the days left until the beginning of the new one. I am counting too, but my countdown is already for the training camp in December. I am very eager to join my teammates, whom I haven't seen in a while, and get back that feeling which I've been missing since crashing out of the Tour de Pologne. It was the low-point of a season that otherwise augured well once I donned the Quick-Step Floors jersey for my first race, in February, the Dubai Tour. That was a really nice way to kick off the season; great weather, sunny and warm, and we won four stages plus the general classification, which had the gift of helping me ease into the pro peloton. Then, shortly after returning to Europe, I got to start my first one-day races, Handzame Classic and Le Samyn. It was a different type of weather than the one in the Emirates, but I liked it, because I got to gain invaluable experience and also notched my first top 10 of the year. Max Schachmann riding in the 2014 World Championships Spring brought two of the Ardennes Classics – Amstel Gold Race and Flèche Wallonne – and the Tour de Romandie, where I came very close to a podium in the prologue. I didn't expect such a result against some of the best riders in the world, many who were there in top shape. That result gave me confidence for the Tour of California, which brought me to the US for the first time in my life. My priority was to perform lead-out duties for Marcel, but despite that, I managed my way to a top 15 overall, which was a solid result considering how hard the week was, with echelons, some tough climbs and an ITT at 2000 meters of altitude. In June, at the National Championships, I was hoping for a good result in the time trial, but I had a really bad day and could finish only fourth. A few days later, in the road race, I tried to make up for the disappointing ITT and was in the mix right from the start. The race was very hard and the peloton was shattered on the first climb of the day. I made the cut, responded to many attacks, but it was difficult against riders who had many teammates in the race. Overall, it was an important experience, from which I really got to learn some things that I hope will come in useful in the future. With the first part of the season wrapped up, I was very motivated to make the selection for the Vuelta a España, but unfortunately that Tour de Pologne crash changed the plans and forced me to draw the curtain on my season and instead start a long road to recovery, which now is only half-way. After the surgery, the doctor told me I need to use the crutches for more than three months, and it was only in October that I began riding the bike on the rollers, 30 minutes every day, just to move the leg. Now I feel much better – the doctor told me that he was satisfied with my progress – but I can tell you that the first week after the surgery was really difficult and painful. Once I came home, it took me some time to get used to it, as all I could do was move from the bed to the couch to watch the races on TV. Since then, I began moving my leg more and even went swimming in the pool, which aided my recovery. The goal is to be fit for the start of the training camp in December and build up. I am aware that I will need a bit more time to regain my condition, but the motivation is there. Of course, I'm not setting the bar too high after such a heavy injury; I have to work hard and see how my body responds before making any plans, but what I can tell you is that I want to make my Grand Tour debut next year; it would be a dream to see this long road to recovery come to an end with me pinning on the number for the start of such a great race.	cc/2019-30/en_head_0044.json.gz/line3453
__label__cc	0.610971	0.389029	Home / Court Decision / Dryden / Fracking / Local Government / Middlefield / Municipal Home Rule Law / New York Court of Appeals / Oil / Sunrise Check Cashing and Payroll Services v. Town of Hempstead / Towns Can Now Use Local Zoning Laws to Ban Fracking Towns Can Now Use Local Zoning Laws to Ban Fracking by Anonymous on Thursday, July 03, 2014 in Court Decision, Dryden, Fracking, Local Government, Middlefield, Municipal Home Rule Law, New York Court of Appeals, Oil, Sunrise Check Cashing and Payroll Services v. Town of Hempstead There are many towns on Long Island that pride themselves on their quaint, small-town characteristics and their colonial history. Residents of these towns often worry that their communities will be tarnished or disrupted by an excavation site in their backyards. However, New York’s highest court has recently upheld the power of local governance to regulate businesses in its borders. According to this ruling, towns have the right to ban fracking by using local zoning ordinances if fracking disrupts the character and integrity of these communities. Fracking is a method of hydraulic extraction. High-pressure fluid is injected into cracks in the earth to release a higher quantity of oil and gas. There is a huge movement in the United States against the use of fracking as it has numerous environmental risks, such as groundwater contamination and earth tremor causation. The towns Dryden and Middlefield, both located in upstate New York, are rural communities that rely heavily on agriculture and small town tourism. In the mid-2000s, two companies, Norse Energy Corp. and Cooperstown Holstein Corp., had tried to develop and extract natural gas in the areas. Responding to rigorous protests, the Town Boards of Dryden and Middlefield banned the use of fracking due to the environmental and health implications involved in the controversial method. Nonetheless, the two companies maintained that state law was on their side and that they had the right to develop in the areas. The New York Court of Appeals has upheld the decisions of the lower courts by ruling in favor of the towns. Pursuant to the Municipal Home Rule Law, by banning fracking, both towns were exercising their local governance rights in the preservation of the character, welfare, and aesthetics of their communities. If fracking threatens the integrity of a town, that town should be able to reject it based on the Home Rule Law. Interestingly, this ruling was not based on any scientific conclusion that fracking is harmful to the environment. Oil companies that want to pursue fracking may do so in areas where fracking is not restricted or banned by local ordinances. Instead, the decision discussed the towns’ objection to fracking on the ground that it would cause heavy traffic congestion in the towns and industrialize the small-town, rural areas. Also, this decision is of note as it comes out the exact opposite of the Court’s February 14, 2013 decision in Sunrise Check Cashing and Payroll Services v. Town of Hempstead, in which the Court declared that the Town of Hempstead could not ban check cashing establishments from the area because its zoning ordinance did not demonstrate that the business had a negative impact on the community. Consequently, reading these decisions together yields an understanding that a town can ban businesses such as adult entertainment and fracking for having negative impacts on the community, but cannot ban check cashing and fast food businesses as there is no objective negative impact. So, the Sunrise case reminds us that this latest decision on fracking is not to be read broadly in garnering an understanding that a town has free rein to prevent any business it dislikes from existing in its borders. Instead, a town must have a legitimate objective belief that the subject business negatively impacts the community, beyond conjecture, in order to block it from the Town’s jurisdiction. This ruling is a victory for local governance, granting towns the power to preserve their character and integrity. It did not address the environmental impacts of fracking in itself, and we must look for future cases in order to obtain clarification on that issue. Tags # Court Decision # Dryden Sunrise Check Cashing and Payroll Services v. Town of Hempstead By Anonymous at Thursday, July 03, 2014 Tags: Court Decision, Dryden, Fracking, Local Government, Middlefield, Municipal Home Rule Law, New York Court of Appeals, Oil, Sunrise Check Cashing and Payroll Services v. Town of Hempstead	cc/2019-30/en_head_0044.json.gz/line3465
__label__cc	0.636945	0.363055	Through a Universe Darkly "An inordinate fondness for beetles." This is how the eminent evolutionary biologist, J. B. S. Haldane, is reported to have replied when asked by theologians to speculate, based on the character of the biological world, what may have motivated the Creator when he undertook its initial design. No doubt, they had hoped for a more inspirational answer. Yet Haldane, a pioneer in mathematical genetics, was absolutely right. He had done the arithmetic, so to speak. At that time over 350,000 species of beetles had been identified, comprising half of all the known insect species. What better insight, then, could one divine concerning divine intention? From all appearances, God played favorites in the animal kingdom, and beetles were at the top of His list. It's not hard to imagine that a latter-day Haldane, steeped in astrophysics instead of natural history, might be confronted with an analogous theological challenge. What does the character of the physical universe that we inhabit reveal about the mind of the Creator who set things in motion some 14 billion years ago? What insights can we derive about Him from our determined investigations of his His creation? "An inordinate fondness for dark energy," would be a fitting response. Following Haldane's lead, let's do the math. According to analysis of the results from the Wilkinson Microwave Anisotropy Probe (WMAP), a satellite launched in 2001 to measure the cosmic background radiation - the electromagnetic afterglow of the primordial Big Bang - to unprecedented precision, our universe consists of 74 percent dark energy, 22 percent cold dark matter and 3.6 percent interstellar gas, leaving a paltry 0.4 percent to the atoms which make up not only nebulae and stars but also the flotsam and jetsam, our home planet for example, that orbit around them. Among these constituents, dark energy is the new kid on the astrophysical block, proposed in 1998 to account for the discovery that the universe is expanding at an ever-increasing rate. Currently no one quite knows what dark energy is. It could be the physical manifestation of the long-suppressed cosmological constant from Einstein's first formulation of his theory of general relativity. Or, it might represent an entirely new type of matter, a background field of particles that permeates the so-called vacuum of space. Whatever dark energy is, its existence is required to make sense of the large scale structure of the universe as indicated by increasingly accurate measurements from experiments such as WMAP. As with dark energy, dark matter is a name given to a form of matter whose composition has not yet been determined. In spite of this, astronomers are convinced that it exists, because, without it, the observed motion of galaxies within galactic clusters would be impossible to explain. Such galaxies maintain long-term stable configurations, yet the mass of these gravitationally bound systems, as estimated by adding up that of their readily observable constituents such as stars, is not sufficient to keep them from flying apart. Something must be missing, and the missing something that solves this problem has come to be called dark matter. Although the detailed properties of dark matter remain a mystery, confidence in its existence continues to increase, supported, in part, by recent observations of the colliding galaxies that form the Bullet Cluster. The most remarkable thing to be said about unremarkable intergalactic gas, which consists of a lone hydrogen atom spaced every cubic meter or so, is that there is so much of it, at least relative to the amount of matter that we find in our immediate neighborhood. Finally we come in our astrophysical inventory to the category of galactic atoms, weighing in at about one-half of one percent of the entire mass of the universe. A significant fraction of these are hydrogen nuclei, engaged in - or acting as bystanders to - the phenomenon of thermonuclear fusion that powers the stars. Hardly meriting arithmetic mention are the the other naturally-occurring chemical elements, the ones that make up everything from planets to plutoids, from people to petunias. Although "rain drops on roses and whiskers on kittens" are, arguably, a few of our favorites things, they and their kind of material stuff appear not to have meant much to the Creator in His grand design, at least as far as the allocation of mass and energy was concerned. Returning now to the theological question that opened this discussion, as in Haldane's time, most theologians - indeed, most believers - today look for inspiration in the prospect of a creator God. Yet attempts at an objective reading of creation as the unfolding of a divine plan leaves one contemplating more a slap-dash muddle than a carefully drafted blueprint. To the extent the Creator had humans in mind in the beginning, He chose bizarrely inefficient means to go about creating them. It would seem that an omnipotent being could have done without adding so much dark energy and so many kinds of beetles to the cosmological mix. As far as science can tell, our species is an unintended consequence of the undirected physical processes that gave rise, first to space and time and matter, and, much later, to life on earth. There is, though, some consolation to be had. God, if he exists, possesses not only an inordinate fondness for beetles and for dark energy, but also an inordinate fondness for puzzles and for wonder. This revelation may be cold comfort for many theologians, but it is a source of unending delight for scientists. Through a Universe Darkly by Marc Merlin is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License. Posted by Marc Merlin at 9:04 PM Labels: creation, dark energy, dark matter, Haldane, theology Evolution and Anti-Magical Thinking The Physics of Unwelcome Surprises	cc/2019-30/en_head_0044.json.gz/line3467
__label__cc	0.64054	0.35946	Dinesh D'Souza, in the Dark about Dark Matter and about Science Of all the attacks leveled against science by the religious faithful, the most insidious are the ones that cast religion and science as comparable approaches to understanding natural the world. In a debate with Christopher Hitchens at Notre Dame this past January conservative author and speaker Dinesh D'Souza showcased a variation of this kind of "we're just two peas in a pod" claim and, in doing so, succeeded in demonstrating a genuine failure to understand how science really works. In the process, he does no great service to religion, either. In making his case for a faith-based approach to science, D'Souza proposes that the existence of God can be employed as a working hypothesis much like any other. And, as with any provisional hypothesis, he says it should be embraced when it helps account for phenomena which have otherwise resisted explantion. Seeking confirmation of this God of the gaps argument - familiar to us from the Intelligent Design controversy - D'Souza turns to astrophysics for an illustration of how science relies on the same kind of speculative thinking that religion does. Here is the background on the example he finds there to exploit. Galaxy cluster ACO 3341, located almost 500 million years away (European Southern Observatory) The Mystery of the Missing Mass In the 1920s, not long after galaxies outside our own Milky Way were first identified, they were seen to arrange themselves into clusters, orbiting about one another, presumably, under the influence of their mutual gravitational attraction. Indeed, the working of gravity in these far, far away places was not unexpected. Contrary to popular conception, Isaac Newton's stroke of genius had not been in observing a falling apple - he was hardly the first to notice that things fall - but in his bold conjecture that the force responsible for causing his proverbial knock on the head was the very same force responsible for the motion of the planets about the Sun. Newton's theory proposed that gravity was universal, applying uniformly to everything, everywhere; to the objects of our everyday experience; to the planets and moons of our solar system; and, presumably, to galaxies, each consisting of hundreds of billions of stars, located millions of light-years away. What took astronomers of the 1930s by surprise was that, when the amount of stuff in these galactic clusters was finally tallied, gravitational accounts did not balance. A census of the visible matter contained within them - stars and dust clouds and other such "luminous" things - resulted in a total mass insufficient to bind them in their mutual orbits. According to calculations the galaxies in these clusters should be flying apart at breakneck speed. The physicists faced a quandary: either Newton had got it wrong, and the force of gravity he proposed was, in fact, not universal, or their exhaustive attempts to catalog the constituents of these galactic clusters had left a significant amount of matter unaccounted for. Bullet Cluster, best evidence to date for the existence of dark matter. At first this astrophysical mystery went by the name "missing mass" and it was presumed to be an artifact of limitations of the observational techniques available at the time. Perhaps, for example, large numbers of dead or dormant stars had gone unobserved and, therefore, uncounted in the celestial tally. But even when astronomers refined their efforts at detection, their gravitational bookkeeping kept coming up short. To make matters worse, after a few decades passed, new astrophysical puzzles were encountered that also hinted at the existence of missing matter in other astrophysical contexts. Finally, and reluctantly, a working hypothesis came to be accepted. The vexing missing mass was assumed to be bound up in a heretofore undetected kind of "dark matter" which was characterized solely by its heft and its failure to shine. Of what it was actually composed, no one had a clue. Next generation detector, Xenon Dark Matter Project Desperately Seeking Dark Matter Now, according to D'Souza, in the same way that physicists have proposed the existence of dark matter as an explanation for an enigmatic phenomenon, the stability of galactic clusters in spite of an apparent insufficiency of mass, so too can we rely on the hypothesis of God to explain other mysteries of the physical world. He contends that such "presuppositions" are valid elements in the construction of scientific theories because they yield immense explanatory payoff; disconnected pieces of a puzzle fall into place and suddenly everything makes sense. Is D'Souza right? Are "materialist" scientists and those who defer to faith-based hypotheses playing by the same rules? To see how the their approaches differ, consider this observation from a recent physics arXiv blog post - First Evidence That Mirror Matter May Fill the Universe? - regarding ongoing efforts to solve this problem. Astronomers call this hidden mass 'dark matter' and physicists around the world are engaged in an increasingly desperate race to find evidence of it here on Earth. [emphasis added] Now imagine, for a moment, an analogous report on the state of current investigations into some phenomenon or other "explained" by D'Souza's God presupposition: Scientists call this hidden cause 'God' and researchers around the world are engaged in an increasingly desperate race to confirm His existence. This comparison, of course, strikes us as ridiculous on its face; no one has ever embarked upon a search for God in order to confirm or refute a physical theory. Good Lord, how could such a search even be conducted? Perhaps more significantly, no teams of researchers have ever engaged in a desperate race to reveal God's existence. What D'Souza fails to appreciate in his casting dark matter as just another presupposition is how unpalatable resorting to such a hypothesis is to physicists, one which they entertain reluctantly because the alternative, a rejection of Newton's theory of universal gravitation, would be even more distasteful. They tolerate "dark matter" as a convenient fiction, but won't rest easy until the composition of this mysterious substance is revealed, or until a more acceptable explanation steps up to replace it. History confirms how earnest physicists have been in wrestling similar "presuppositions" to the mat. Interestingly enough, three examples involve a search for missing mass of one variety or another. Neptune from the Voyager 2 flyby (1989). A Missing Planet Found The first hidden matter search came about with the discovery of Uranus by Sir William Herschel in 1781. With Newton's theory in hand, astronomers were able to calculate the orbit of the newly discovered planet, but by the early 19th century it had become clear that discrepancies existed between the predicted trajectory of Uranus and that which had been meticulously observed. These scientists were presented with a dilemma not unlike the one that their counterparts would face a century later: either Sir Isaac had gotten things wrong with his theory of gravity or a very significant mass had gone missing. Perhaps it took the form of a yet undetected outlying planet which was perturbing the motion of Uranus in its path around the Sun? As disagreement between theoretical calculations and observational evidence became more and more convincing, a desperate race ensued. The hidden culprit, the planet Neptune, was revealed by Urbain LeVerrier in 1846. First neutrino detection in a bubble chamber (1970). A Missing Particle Detected In a second example of a missing mass mystery, by 1930 the radioactive decay of atomic nuclei into constituents components had been long-observed and carefully measured, yet, as a result, a vexing question arose. When the energies of all the particles emerging from the site of such a decay were added up there was an unexpected energy shortfall. Either a new kind of particle had fled the scene undetected, carrying with it just the right amount of energy (and, according to Einstein, mass) or the long-cherished principle of conservation of energy - far more fundamental for physics than even Newton's universal gravitation - would have to be abandoned. This fugitive particle, dubbed the neutrino by Enrico Fermi in 1934, eluded capture for more than two decades; science did not breathe a sigh of relief until Clyde Cowan and Frederick Reines detected it directly in 1956. Schematic of Earth moving through the hypothetical aether. The Aether goes Missing - with a Payoff As a final example of the search for a missing substance - and an illustration that presuppositions demand verification - consider the state of the physics of electromagnetic radiation - i.e. light - in the late 19th century. About the time of the American Civil War James Clerk Maxwell, in what has become to be regarded as the first unified field theory of physics, demonstrated mathematically that light traveled as a wave, not unlike the way waves spread across the surface of a body of a water. In much the same way that other wave phenomena required a supporting medium - for example, some gas or mixture of gases for sound - it was presupposed that a medium was necessary for the propagation of light, something that pervaded every nook and cranny of space. Confident in this hypothesis, physicists even gave the conjectured substance a name; it was called the luminiferous (light-bearing) aether. An ingenious experiment to detect the existence of this mysterious stuff was undertaken by Albert Michelson and Edward Morley in 1887. It failed utterly, but with that failure was planted the seed of Einstein's theory of special relativity which would blossom less than 20 years later. As these examples illustrate, what Dinesh D'Souza does not understand is that for scientists a presupposition, better characterized as a working hypothesis, is not the end of an investigation, but a starting point. Presupposing the existence of God as an explanation, as D'Souza suggests, offers no avenue for further research, it is nothing more than prescription for investigative complacency; one might as well hang a "gone fishin'" sign on the laboratory door. Regardless of the spiritual rewards that some derive from a belief in God, as a scientific hypothesis it is worse than a blind alley; positing God as an explanation discourages further research, sometimes benignly, by declaring, falsely, that a difficult problem has been solved, and at other times malignly, by intimidating those who dare to seek honest answers based in physical law. It is important to point out that D'Souza's attempt to exploit the dark matter hypothesis as evidence of the comparability of scientific and religious reasoning about the world is just the latest round in the assault on science by those who, like him, feel that a purely materialist view of nature is incompatible with their deeply held religious beliefs. In the late 1980s they took aim at the theory of evolution with their Intelligent Design hypothesis and were, in short order, discredited. Probing for vulnerabilities elsewhere they have recently turned their sights on astrophysics and neuroscience, hoping for more favorable battlefields. But, as Ken Miller, professor of biology at Brown University and a practicing Roman Catholic, noted in his essay, The Flagellum Unspun, which convincingly refutes claims of "irreducible complexity", the cornerstone of Intelligent Design theory, ... the struggles of the intelligent design movement are best understood as clamorous and disappointing double failures – rejected by science because they do not fit the facts, and having failed religion because they think too little of God. Sadly, Dinesh D'Souza seems compelled to repeat this same mistake, looking for confirmation of his belief in God in the wrong places, misrepresenting the enterprise of science and futilely struggling to insert the Deity in the forever-narrowing gaps in our understanding of the natural world. Dinesh D'Souza, in the Dark about Dark Matter and about Science by Marc Merlin is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Posted by Marc Merlin at 10:00 AM Labels: aether, Christopher Hitchens, D'Souza, dark matter, debate, Dinesh D'Souza, ether, God of the gaps, Hitchens, missing mass, Neptune, neutrino Leo Tomasevich said... It appears that you have misunderstood D'Souza’s argument in regards to the existence of G-D. First, many times, atheist want theist to demonstrate the existence of G-D without using the Bible, religious doctrine or Church history to do so. Ergo, what D'Souza is doing in this debate, is presenting a philosophical syllogism, that uses logic and reason to demonstrate its principle. He is not saying that religion and science are equal or that they are somehow the same and that they should be understood in the very same way. This is your interpretation of his argument. Secondly, when making a philosophical argument, one is trying to demonstrate the best explanation for something. “Proof” is a word used in other disciplines – not in philosophy. One other thing – the best explanation for something is defeasible. That is to say, that one can defeat an argument that proposes the best explanation for something by showing a “better” explanation. Dinesh D'Souza, in the Dark about Dark Matter and ...	cc/2019-30/en_head_0044.json.gz/line3468
__label__cc	0.673245	0.326755	Kwanzaa: The Real Story Where Do I Go? by Neta Jackson Engaging Father Christmas by Robin Jones Gunn Quills And Promises by Amber Miller Dark Pursuit by Brandilyn Collins One Perfect Day by Lauraine Snelling Here I go, getting myself in trouble again, but sometimes you gotta' do what you gotta' do! I got a few e-mails (the ones from last year know better snort) from people who have asked me why I did a post on Christmas but I don't do one on Kwanzaa, and they wanted to know why. Well here's my answer... I am a born-again, evangelical Christian. Christmas is the commemoration of the birthday of my Lord and Savior, Jesus Christ. Kwanzaa, is a black-oriented holiday invented in 1966 by Dr. Maulana Karenga. On September 17, 1971, this same man was handed one to ten years in prison because of charges filed in 1970 where Karenga and two of his cohorts tortured two women that he accused of trying to kill him. Karenga beat the women with an electrical cord and a karate baton after ordering them to strip naked. The one woman had a hot soldering iron put in her mouth and placed against her face. That not being sufficient torture, Kurenga also put detergent and running hoses in their mouths. But ya' know who am I to throw stones...we all make mistakes...rightttttt! Initially Kwanzaa developed because Karenga held a hostility toward Western religion. He wrote in his 1980 book, Kawaida Theory, "denies and diminishes human worth, capacity, potential and achievement. In Christian and Jewish mythology, humans are born in sin, cursed with mythical ancestors who've sinned and brought the wrath of an angry God on every generation's head." He similarly opposed belief in God and other "spooks who threaten us if we don't worship them and demand we turn over our destiny and daily lives." Thus, Karenga explained in his 1977 Kwanzaa: Origin, Concepts, Practice, "Kwanzaa is not an imitation, but an alternative, in fact, an oppositional alternative to the spookism, mysticism and non-earth based practices which plague us as a people and encourage our withdrawal from social life rather than our bold confrontation with it." The holiday "was chosen to give a Black alternative to the existing holiday and give Blacks an opportunity to celebrate themselves and history rather than simply imitate the practice of the dominant society." Since then, the holiday has gained mainstream adherents, and Karenga has altered its justification so as not to alienate practicing Christians: "Kwanzaa was not created to give people an alternative to their own religion or religious holiday," he writes in Kwanzaa: A Celebration of Family, Community, and Culture, published in 1997. So, would I as a Christian, American, black woman celebrate this, this Kwanzaa...not with a ten foot pole! I know there will be people out there who get riled up by my comments. Too bad...so sad! The story of Christmas comes from the Bible. Here is the way it is told by Luke 2:7-16... And she brought forth her first born son, and wrapped him in swaddling clothes, and laid him in a manger; because there was no room for them in the inn. And there were in the same country shepherds abiding in the field, keeping watch over their flock by night. And lo, the angel of the Lord came upon them, and the glory of the Lord shone around about them; and they were sore afraid. And the angel said unto them, "Fear not: for, behold, I bring you good tidings of great joy, which shall be to all people. For unto to you is born this day in the city of David a Savior, which is Christ the Lord. And this shall be a sign unto you; ye shall find the babe wrapped in swaddling clothes, lying in a manger." "Glory to God in the highest, and on earth peace, good will toward men." And it came to pass, as the angels were gone away from them into heaven, the shepherds said one to another, "Let us now go even unto Bethlehem, and see this thing which is come to pass, which the Lord hath made known to us." And they came with haste, and found Mary, and Joseph, and the babe lying in a manger. These aught to hold you for Christmas Eve...Enjoy! Where Do I Go? Thomas Nelson (December 9, 2008) Neta Jackson As a husband/wife writing team, Dave and Neta Jackson are enthusiastic about books, kids, walking with God, gospel music, and each other! Together they are the authors or coauthors of over 100 books. In addition to writing several books about Christian community, the Jacksons have coauthored numerous books with expert resource people on a variety of topics from racial reconciliation to medical ethics to ministry to kids in gangs. Dave and Neta live in Evanston, Illinois, where for twenty-seven years they were part of Reba Place Church, a Christian church community. They are now members of a multi-racial congregation in the Chicago area. They're trying something new! Not just new for them, but something completely new in Christian fiction: “Parallel novels,” two stories taking place in the same time frame, same neighborhood, involving some of the same characters living through their own dramas and crises but interacting with and affecting one another … just the way it happens in real life. It’s something that only a husband and wife writing team could pull off. While Neta has Where Do I Go?, her husband Dave has written Harry Bentley's Second Chance. A story of seeking-and finding-God's will in unlikely places. Gabrielle Fairbanks has nearly lost touch with the carefree, spirited young woman she was when she married her husband fifteen years ago. But when the couple moves to Chicago to accommodate Philip's business ambitions, Gabby finds the chance to make herself useful. It's there she meets the women of Manna House Women's Shelter; they need a Program Director-and she has a degree in social work. She's in her element, feeling God's call on her life at last, even though Philip doesn't like the changes he sees in her. But things get rough when Philip gives Gabby an ultimatum: quit her job at the shelter or risk divorce and losing custody of their sons. Gabby must take refuge, as in the song they sing at Sunday night worship: "Where do I go when there's no one else to turn to? . . . I go to the Rock I know that's able, I go to the Rock." Romantic Times Book Reviews says, “Exquisite characters coupled with God's mercy and love emanate from each page.” Publisher's Weekly adds, “Jackson's Yada Yada series has sold half a million copies, and this new offshoot series ... promises the same.... The book's dramatic ending ... leav[es] readers eager for the next installment in the series.” To read the Prologue and first Chapter of Where Do I Go?, go HERE Engaging Father Christmas FaithWords (October 30, 2008) Miranda Carson can't wait to return to England for Christmas and to be with her boyfriend, Ian. She has spent a lifetime yearning for a place to call home, and she's sure Carlton Heath will be it, especially when a hinted-at engagement ring slips into the conversation. But Miranda's high hopes for a jolly Christmas with the small circle of people she has come to love are toppled when Ian's father is hospitalized and the matriarch of the Whitcombe family withholds her blessing from Miranda. Questions run rampant in Miranda's mind about whether she really belongs in this cheery corner of the world. Then, when her true identity threatens all her relationships in unanticipated ways, Miranda is certain all is lost. And yet...maybe Father Christmas has special gifts in store for her after all. If you would like to read the first chapter of Engaging Father Christmas, go HERE Quills And Promises Barbour Publishing, Inc (May 28, 2008) Hi, I'm Amber, but my friends call me Tiff, short for Tiffany, my first name. I am in my 30's, married the love of my life in July 2007, and live in beautiful Colorado just east of the Front Range of the Rockies, but I love to travel and visit new places. Ultimately, my dream is to own horses and live in a one-level rancher or log cabin nestled in the foothills of the mountains. For now, I will remain where I am and do what I love—design web sites and write. Amber's very first book, Promises, Promises, released in February 2008. It's a historical fiction set in Delaware during the Colonial period and the Great Awakening. The other 2 books in the series are this current one, Quills And Promises (July 2008) and Deceptive Promises (December 2008). In 2009, they will be repackaged for a state set entitled Delaware Brides. She has also sold another series set in historical Michigan during the Industrial Revolution. The 3 books in that series will begin releasing in May 2009 and will be repackaged in 2010 as Michigan Brides. -- Separated from Madison when he leaves to fight the French and Indians, Elanna Hanssen must choose between her heart and her head, especially when Madison's integrity is questioned. -- "Trust in the Lord with all thine heart, and lean not until thine own understanding. In all thy ways acknowledge Him, and He shall direct thy paths." ~Proverbs 3:5-6 Innocence paired with wisdom beyond her years. With these traits, Elanna Hanssen unwittingly captures the attentions of Major Madison Scott. Her honest desire to understand the war fascinates him, and he resolves to get to know this perspicacious young lady better. When his military duty separates them, they begin a correspondence, cautiously baring their hearts to each other. Elanna has never known emotions like this before, but she is drawn to the integrity she sees in her major. Wh a local news reporter questions the major's credentials and activities, however, will she allow her heart or her head to rule? Can true love grow over such distance and around such obstacles? If you'd like to read the first chapter of Quills And Promises, go HERE. Dark Pursuit Zondervan (December 1, 2008) Brandilyn Collins is known for her trademark Seatbelt Suspense®. She is currently working on her 20th book. For chances to win free copies of her work, join her Fan Club on Facebook. Here’s what Brandilyn has to say about why she wrote Dark Pursuit: In John Milton’s Paradise Lost Satan’s followers, kicked out of heaven, boast about storming the gates and reclaiming their territory. Beelzebub scoffs at their boasting as merely “hatching vain empires” and suggests a different revengeful scheme: seduce mankind away from God. So Satan visits the Garden of Eden to teach humans the very thing he and his cohorts have learned to be futile—the dark pursuit of hatching their own vain empires instead of following God. He presented man with this “gift” of death, disguised as life. And man fell for it. Upon this theme of man’s fall and spiritual blindness, I created the characters and events in Dark Pursuit. The story clips along at a fast pace, with much symbolism running underneath. Dark Pursuit—A twisting story of murder, betrayal, and eternal choices Novelist Darell Brooke lived for his title as King of Suspense—until an auto accident left him unable to concentrate. Two years later, reclusive and bitter, he wants one thing: to plot a new novel and regain his reputation. Kaitlan Sering, his twenty-two-year-old granddaughter, once lived for drugs. After she stole from Darell, he cut her off. Now she’s rebuilding her life. But in Kaitlan’s town two women have been murdered, and she’s about to discover a third. She’s even more shocked to realize the culprit—her boyfriend, Craig, the police chief’s son. Desperate, Kaitlan flees to her estranged grandfather. For over forty years, Darell Brooke has lived suspense. Surely he’ll devise a plan to trap the cunning Craig. But can Darell’s muddled mind do it? And—if he tries—with what motivation? For Kaitlan’s plight may be the stunning answer to the elusive plot he seeks... Read the first chapter of Dark Pursuit, HERE. One Perfect Day Today, Lauraine Snelling is a member of the more than Two Million Books In Print club, but when she first began, she was a mother of three teenagers with a simple dream to write “horse books for kids.” All told, she has over 50 books published. She thinks. She’s not sure. She’d rather write them than count them. Lauraine’s work has been translated into Norwegian, Danish and German as well as produced as books on tape. Awards have followed her dedication to “telling a good story”: the Silver Angel Award for An Untamed Land and a Romance Writers of America Golden Heart for Song of Laughter. Helping others reach their writing dream is the reason Lauraine teaches at writer’s conferences across the country. She mentors others through book doctoring and with her humorous and playful Writing Great Fiction tape set. Lauraine also produces material on query letters and other aspects of the writing process. Her readers clamor for more books more often and Lauraine would like to comply, if only her ever-growing flower gardens didn’t call quite so loudly over the soothing rush of the water fountains in her back yard and if the hummingbirds weren’t quite so entertaining. Lauraine and husband Wayne have two grown sons and a cockatiel named Bidley, who loves to tease their Basset Hound named Chewy. Two mothers end up more closely connected that they could dream...and yet they are strangers to one another. The first has two children--twins, a boy and girl, who are seniors in high school. She wants their last Christmas as a family living in the same home to be perfect, but her husband is delayed returning from a business trip abroad. And then there's an accident--a fatal one involving a drunk driver. Meanwhile, the other mother has a daughter who needs a new heart, and so the loss of one woman becomes the miracle the other has desperately prayed for. While one mother grieves, and pulls away from her family, the other finds that even miracles aren't always easy to receive. If you would like to read the first chapter of One Perfect Day, go HERE	cc/2019-30/en_head_0044.json.gz/line3472
__label__wiki	0.863694	0.863694	So the biggest thing going on in the Chicago area this weekend is the Blue Whiskey Independent Film Festival at the AMC Randhurst movie theatre in Mount Prospect. Actually, Lollapalooza is the hottest thing in town right now but BWiFF has its merits as well. The annual event continues tonight with the feature film Jasmine, a murder mystery set in Hong Kong, and four short films. Tomorrow night, Open Tables, a feature film set in trendy Chicago and Paris restaurants will be screened, preceded by a selection of short films. On Sunday, the activity moves to Star Cinema Grill in Arlington Heights as Blue Whiskey holds its 2016 Blue Glass Awards ceremony, followed the music documentary Ron Pope: One Way Ticket. I’ve covered the Blue Whiskey Independent Film Festival more extensively in previous years, but a busy work schedule wreaked havoc with my blog plans for this week. Chicago alt rock station WXRT has plenty of Lollapalooza programming going on this weekend, with backstage coverage from Grant Park and interviews with founder Perry Farrell and several of the musicians performing. Marty Lennartz, a master of the art of conversation, whether he’s talking to a world-famous band, a local act, or even one of the station’s fans, will be doing the bulk of the interviews. You can also find helpful Lollapalooza tips in this week’s Reader, Redeye, and Chicago Sun-Times. If you still have a copy of last Sunday’s Chicago Tribune laying around, there’s a two-page spread in the Arts and Entertainment section with longtime rock critic Greg Kot’s recommendations and a complete grid of the Lollapalooza schedule. Also, the current issue of Streetwise has a rundown compiled by Micaela Berz of Lollapalooza After Party events taking place at Metro, The Vic, Lincoln Hall, House Of Blues, and several other locations. Streetwise has been helping homeless people get their lives together for a few decades now, and its coverage of local entertainment has been particularly impressive lately. Pick up a copy for $2 from one of the vendors downtown. Bobby Elliott, an original and current member of The Hollies, and Danny Handley of The Animals will be performing at a Blues and Rock Evening fundraising event tomorrow, July 30, at Cafe Cargo in Foulridge in the UK. They’re looking to raise funds to preserve an area called the Green Fields of Colne. There will be a showcase of blazing guitars this Sunday night when rock hero Jeff Beck and blues icon Buddy Guy share the bill at Ravinia. Bryan Ferry comes to Ravinia next Saturday, August 6. Tellin’s Tales Theatre’s Classroom Drama - Teachers Tell Tales Out of School. . . wraps up this weekend at Prop Thtr on Elston Avenue. The show features Lily Be, Beth Ann Bryant-Richards, and Tekkie Lomnicki, along with a Substitute Teacher for each show. Jack Murphy gets his turn tomorrow night when he performs I Was The Walrus, a piece about how he taught a Beatles class at a local high school. Tickets are $20, show time is 8:00 p.m. tonight and Saturday, and 7:00 p.m. on Sunday. You love his books, now see him rock. Noted journalist Ken Sharp, who created the very cool Play On! Power Pop Heroes series (I own all three volumes) will be performing at the Molly Malone’s club tomorrow night (July 30), as part of International Pop Overthrow - Los Angeles. L.A. is the birthplace of the David Bash-founded International Pop Overthrow. Tickets went on sale this past Thursday for the Robyn Hitchcock show with special guest Emma Swift at City Winery Chicago. Elsewhere on the concert scene, Guided By Voices are coming to Metro on September 3. The trailer for director Ronny Howard’s documentary The Beatles: Eight Days A Week - The Touring Years has been popping up on various websites (Huffington Post and Rolling Stone, for example) and it looks like all that performance footage of the band’s early days is going to make for some fascinating widescreen viewing and listening. L7, known for provocative, hard-edged, and melodic tunes like “Pretend We’re Dead” and “Shitlist,” will be rocking down the walls at Metro next Saturday night, August 6. Who’ll stop the rain? A concert by The Fortunate Sons, a Creedence Clearwater Revival tribute band scheduled for tonight at the outdoor Fred P. Hall Amphitheater in Palatine, was cancelled due to complications with the weather. Fest For Beatles Fans - Chicago - August 12–14 at Hyatt Regency Hotel Wizard World Comic Con - August 18–21 at Donald A. Stephens Center Abbie Hoffman Died For Our Sins Festival - August 19–21 at The Den Theatre The Go-Go's - August 19 Ravinia Matthew Sweet with Material Reissue - September 9 - Park West Riot Fest - September 16–18 in Douglas Park Lush - September 18 at The Vic The Buzzcocks - September 22 - The Vic The Smithereens - September 25 at City Winery Brian Wilson Celebrates Pet Sounds 50th Anniversary - October 1 at The Chicago Theatre Nick Lowe with Josh Rouse - October 15, October 17 at Old Town School of Folk Music Elvis Costello’s Imperial Bedroom And Other Chambers Tour - October 29 at The Chicago Theatre Sidewalk Society - Self-titled EP Sidewalk Society was one of the acts recruited by the UK indie label Fruits de Mer for its limited-edition Fashion – Songs Written By David Bowie album earlier this year. The California-based trio’s cover of “Can’t Help Thinking About Me” will also soon be available on its own self-titled, colored-vinyl EP, due out on FdM in early August. The other three tracks are also covers—Bowie’s “Let Me Sleep Beside You” and a pair of songs originally done by the less-famous but still tribute-worthy English band The Action. Sidewalk Society has covered The Rolling Stones and The Kinks in the past, and they’re at the top of their Brit Invasion game again on this effort. David Bowie is often thought of as having emerged in the 1970s, but his “Can’t Help Thinking About Me” single was released in 1966. Sidewalk Society’s version calls to mind the earliest work of The Who, thanks to Jerry Buszek’s propulsive drumming. At the same time, the vocals (I’m not sure whose since Buszek, guitarist Danny Lawrence, and bassist Dan West are all listed as singers) capture Bowie’s charismatic approach. The seductive intentions of “Let Me Sleep Beside You” are set to an exotic arrangement that includes a touch of soul as well as string accompaniment. Lawrence explains on the FdM press release that Sidewalk Society used its “passion for great albums of that era” to reinvent a pair of demo versions by The Action. “Look At The View,” with flower power sentiments like, “Sun is shining, plenty of light,” is authentic psychedelia infused with power pop. “Strange Roads” finds Sidewalk Society successfully experimenting with a more hard-edged 1970s rock feel. The trio’s 2012 full-length effort Venus, Saturn and The Crescent Moon is available on its Bandcamp page. Alvvays (pronounced Always) will be one of the headline acts this Sunday night at Wicker Park Fest. When I reviewed the The Toronto-based band’s self-titled debut on January 26, 2015, I noted, “Lead singer-guitarist Molly Rankin’s ethereal vocals weave heartache within irresistible melodies and twangy guitars in much the same way Dee Dee Penny does with the Dum Dum Girls.” Rocket From The Crypt and The Coathangers are among the other acts scheduled to perform this weekend. There is a $10 suggested donation. Elvis Costello’s Imperial Bedroom And Other Chambers Tour comes to The Chicago Theatre on October 29. Tickets went on sale earlier today. Tickets will go on sale tomorrow morning for the final performance of Brian Wilson Celebrates Pet Sounds 50th Anniversary in its entirety on October 1 at The Chicago Theatre. Al Jardine and Blondie Chaplin will be Mr. Wilson’s special guests. According to a recent post on his Facebook page, Graham Nash will be talking with host Liz Kershaw about his career on the BBC Radio 6 show tomorrow, July 23. The opening performance and after party for Tellin’s Tales Theatre’s Classroom Drama - Teachers tell tales out of School. . . will be held tonight at Prop Thtr on Elston Avenue. The show, featuring Lily Be, Beth Ann Bryant-Richards, and Tekki Lomnicki, runs this weekend and July 29–31. Beatles fans, take note: Jack Murphy will perform I Was The Walrus, a piece inspired by the band, next Saturday night. Minds will be bending to the beat tomorrow night at the Burlington Bar on Fullerton in Chicago when Psychedelic Saturday takes place. The Red Plastic Buddha, the Chicago-based band whose Songs For Mara album came in at number on the 201 Broken Toy Favorite Releases List, will be performing. The other acts on the bill are Dark Fog; Warhorses, coming in from Detroit; and Diagonal, performing its first show. DJ Psyched Alex will keep the music flowing between sets. The event starts at 8:30 p.m. Last week I mentioned that Matthew Sweet is coming to Park West in Chicago on September 9, and now there’s more good news about that show. Material ReIssue, with singer-guitarist Phil Angotti joining original Material Issue members bassist Ted Ansani and drummer Mike Zelenko, will be the opening act. Tickets are now on sale. Kate Fagan from Chicago’s long-time ska band Heavy Manners, is re-releasing her 1980s solo effort I Don’t Wanna Be Too Cool, with two previously unreleased tracks on August 8. Fagan will be a special guest at the Neo New Wave Thursdays Haven at the Debonair Social Club on August 10 from 10:00 p.m. to 2:00 a.m. If you think the band names 13 Tikis, Amazing Heeby Jeebies, Hay Shakers and Chicago Blues Angels sound fun, you’ll probably want to drop by Braurhouse in Lombard next Friday, July 29 because all of the above-mentioned acts will be sharing the bill. Tickets are now available for Mary-Arrchie Theatre’s Abbie Hoffman Died For Our Sins Festival XXVIII, which takes place the weekend of August 19–21 at The Den Theatre. This will be the final version of the annual virtually non-stop, freewheeling celebration of music, theatre, and comedy. I haven’t missed a single one over the years, and I definitely will be there for XXVIII. The Fortunate Sons, a Creedence Clearwater Revival tribute band that uses vintage instruments and clothing to capture the rambunctious spirit of the Fogerty brothers and company, will be performing at the outdoor Fred P. Hall Amphitheater in Palatine next Friday night. We just can’t keep anything nice around here. The Blue Whiskey Independent Film Festival, which was one of the coolest things in my hometown of Palatine, has moved its operations to AMC Randhurst 12 in Mount Prospect. This year’s event, which kicks off Sunday, July 24, will offer five Feature Film Official Selections, 20 Short Film Official Selections, and five World Cinema Selections (Out Of Competition). And finally, just a quick shoutout of support to Leslie Jones of Saturday Night Live, who has been deluged with hate-filled nonsense on social media for daring to take part in an all-female recasting of Ghostbusters. Keep up the good work, Leslie. Because you’re talented, funny, and doggone it, real people like you. Plan Ahead: Lollapalooza - July 28–31 in Grant Park Jeff Beck and Buddy Guy - July 31 at Ravinia Bryan Ferry - August 6 at Ravinia L7 - August 6 at Metro Fruits de Mer Records Guide To The Hitchhiker’s Guide To The Galaxy For anyone who feels Broken Hearted Toy has been over-saturated with Chicago events lately, here’s a post that’s light years away from my hometown. England’s eccentric and consistently adventurous indie label Fruits de Mer has just launched another batch of limited-edition seven-inch singles on colored vinyl. One of those records is a tribute to “Journey Of The Sorcerer,” the theme song from the 1970s UK sci-fi miniseries The Hitchhiker’s Guide To The Galaxy. The hilarious book by Douglas Adams was also adapted for radio and film in the past, and now it’s inspiring psyche/prog rock musicians. The Fruits de Mer Records Guide To The Hitchhiker’s Guide To The Galaxy, AKA “Journey Of The Sorcerer,” features three different versions of the theme song by regulars from the FdM roster. Each of them comes through with flying—make that warp speed—colors. The three instrumentals on this record are so completely different from each other that anyone not familiar with “Journey Of The Sorcerer” would likely not realize they’re all the same composition. Australasia's version is spacey and triumphant, and the one that most resembles the theme from another cult classic, Doctor Who. Guitarist Icarus Peel takes a more mysterious approach while delving into sultry modern jazz. Blue Giant Zeta Puppies, living up to their rambunctious name, provide some high-energy transportation to the end of the universe. Fruits de Mer has always rewarded its customers, and in this case, anyone who orders “Journey Of The Sorcerer” will get a bonus CD with material by Quantum Surf Rocket Garage Dolls, Australasia, and Pete Bingham from the band Sendelica. Gary Ritchie - pop-ti-mis-tic Chicago-based multi-instrumentalist and singer Gary Ritchie’s career in power pop includes his time with one of the genre’s earliest bands Loose Lips. He’s also performed with Mike Jordan and The Rockmatics. As on his earlier solo efforts, Ritchie fills pop-ti-mis-tic with catchy 1960s style arrangements fueled by ringing guitars. His voice can still come across as a little hokey at times, but the lyrics feature clever imagery and wordplay. On the funny and very Beatlesque “Million Dollars,” Ritchie dreams of various achievements—like playing shortstop for the Cubs in a World Series—that would make him more appealing to a woman who has just given him the cold shoulder. “Let’s Pretend” and “Book Of Answers” are catchy pop songs about unrequited love while on “It’s Not Automatic,” it’s the guy who’s bailing on the relationship. “Friend Of Old” has a more somber approach, as Ritchie pays tribute to bass player Tom “Pickles” Piekarski, who was probably best known for his work with The Bad Examples, and widely respected on the local music scene. Ritchie taps into Buddy Holly on “Carol Says” while “Perfect Girl,” about a lifetime infatuation with model in a magazine, evokes an early 1960s sock hop. “Subtle As A Freight Train” shows Ritchie at his best, as he tosses nostalgia aside and goes for a harder edged power pop arrangement. Remembering Leslie Witt Photo from the WXRT website. When WXRT news anchor Mary Dixon announced early this morning that Leslie Witt, a longtime air-personality at the FM alternative rock station had passed away from ovarian cancer, I’m sure it shocked and saddened a lot of people. WXRT is a rarity in the radio business in that it has kept the same format for decades while most of its deejays build long-term relationships with their listeners. Even by those standards, Witt’s tenure was an amazing one. She had already been onboard for a year and a half when I did a piece about WXRT for a local free paper called Metro Entertainment Calendar back in 1979. This was when the station was still located on Belmont Avenue. I spoke with her on the phone as part of a series of interviews I did with the air staff. Witt was just as friendly and easy going as she was on the radio as we talked about her “Hangover Special” show on Saturday and Sunday mornings, as well as her 2:00 a.m. to 6:00 a.m. shift on Monday through Wednesday. The WXRT staff paid tribute to and shared memories of Witt throughout today on Facebook, the station’s website, and on the air. Several remarked on the support she gave them, her courageous struggle against her disease, and how she was still going to rock concerts even within the past few weeks. Witt’s family is asking fans to consider making a donation to the Ovarian Cancer National Alliance. The Dandy Warhols are coming to Park West on September 24. Here’s an official Broken Hearted Toy welcome to all of those who have come to Chicago for the Pitchfork Music Festival this weekend in Union Park. It kicked off today at 3:00 p.m. and runs until 10:00 p.m. on Sunday. This week’s edition of The Reader has a rundown on all the acts that will be performing, and carries on the publication’s tradition of having a cool Pitchfork illustrated front cover. Posters of Pitchfork covers from previous years are available from The Reader. Also check out knowledgeable rock critic Greg Kot’s cheatsheet in today’s Chicago Tribune. The annual Southport Art Festival is being held tomorrow and Sunday at Southport and Waveland. Admission is free, and a full page ad in the Redeye newspaper promises live music, but I wasn’t able to find any details on the web. If past Southport fests are any indication, there will be a lineup of about five local acts each day. Tickets went on sale today for upcoming shows by Matthew Sweet (September 9) and The Dandy Warhols (September 24) at Park West. Piano accompanist David Drazin will be providing a live soundtrack to Fritz Lang’s highly influential and critically acclaimed silent film Destiny tomorrow (July 16) at 3:00 p.m. at the Gene Siskel Film Center. I first met Drazin back in the late 1980s when we founded the Famous In The Future comedy group with Frank Carr and Lake Sirmon. Minds will be bending to the beat next Saturday, July 23 at the Burlington Bar on Fullerton in Chicago when Psychedelic Saturday takes place. The Red Plastic Buddha, the Chicago-based band whose Songs For Mara album came in at number four on the 2014 Broken Toy Favorite Releases List, will be performing. The other acts on the bill are Dark Fog; Warhorses, coming in from Detroit; and Diagonal, performing its first show. DJ Psyched Alex will keep the music flowing between sets. The event starts at 8:30 p.m. Self-published author Susan Kaye Quinn will share secrets on how she’s successfully marketed over 50 sci-fi books next Wednesday, July 20 at the Barnes and Noble store in Schaumburg. Quinn is a member of the SCBWI (Society of Children’s Book Writers and Illustrators) group I’ve belonged to for a number of years. Her workshop is titled Series and Serials – Writing Stories That Keep Your Readers Coming Back For More. The hard-edged and satirically lethal power pop band Van Go will be performing on Saturday, July 30 at Martyrs’ on Lincoln Avenue. In reviewing of Van Go’s The Long Lost Last Call album, I noted, “Lead vocalist-guitarist Dave Sippel composes hard-hitting songs that combine biting lyrics with strong melodies.” Freema Agyeman. who played the cool and courageous Martha Jones to David Tennant’s emotionally complicated Doctor on Doctor Who, was in Chicago recently filming scenes for the second season of the Netflix sci-fi show Sense8. The Artist Formally Known As Vince (lots of people get the name wrong and say ‘Formerly’) will be performing next Wednesday at Martyrs’ on Lincoln Avenue. TAFKAV is a fun co-ed indie band that has performed a number of times at International Pop Overthrow - Chicago. New City came out with its annual Music 45 - Who Keeps Chicago In Tune issue, with blues legend and Rolling Stones pal Buddy Guy coming in at number one. There’s a good variety in the choices, which include Chicago Symphony Orchestra music director Richard Muti; musician/producer Jeff Tweedy of Wilco; hip-hop pioneer/actor Common; jam band Umphrey’s McGee, and Smashing Pumpkins. This issue also has a preview of Lollapalooza (July 28–31), along with three full-color pages of Lollapalooza posters. New City is available for free in newspaper boxes and venues around downtown and on the north side. Mary-Arrchie Theatre’s final Abbie Hoffman Died For Our Sins Festival - August 19–21 at The Den Theatre Roxy Swain - Beneath Full Moonlight Roxy Swain’s third album Beneath Full Moonlight had its digital release back in April but the vinyl edition came out via a release party at the Elbo Room on Lincoln Avenue just last month. Written by all four band members, these songs once again showcase lead vocalist-rhythm guitarist Roxy Swain’s evocative vocals, while exploring rock, soul, and Country and Western. There’s a variety of emotions at work here as well, mostly set to melodic, mid-tempo arrangements led by Matt Walters on guitar and keyboards. “Set The House On Fire” presents an escapee from an unhappy relationship, and whether the title act was real or metaphorical, she’s feeling empowered and guilt free. An entirely different set of emotions emerges on the Country and Western/alt rock tune “Ash In My Mouth,” as a woman mourns being left behind by someone she loved. Grooving to the rhythm section of drummer Chuck Harling and bassist Jeffrey Altergott, Swain’s at her most playful on “She Who Hesitates” as a woman cruising the dating scene after too many years of waiting for the perfect guy. Walters’ guitar playing propels “The Conversation,” another emotional song about a stagnant relationship. A few songs on Beneath Full Moonlight sound too much the same, but the catchy “Falling Below” benefits from Swain’s sultry approach. “Son” is easily the most energetic track; sounding at times like it could spin out of control. But in a good way. Photo from Savages Facebook page. The Pitchfork Music Festival returns next weekend to Union Park, with a massive schedule that includes Brian Wilson, Savages, Beach House, Broken Social Scene, Twin Peaks, Sufjan Stevens, and Super Furry Animals. Local publication Innerview just put out a full issue devoted to the event. You can pick up a copy at Reckless Records on Madison downtown. Penn Jillette and director Adam Rifkin were in town last night for the Chicago premiere of their gruesome but consistently funny satire Director’s Cut at the Gene Siskel Film Center. There was a private screening and meet-and-greet for fans who had helped out with the movie’s crowdfunding campaign. Jillette and Chicago native Rifkin were also on hand for a second show, providing humor and interesting anecdotes as they took questions from audience members afterward. Chicago indie rock musician Jim Gwynn posted on Facebook that his band JIP, whose recording efforts have drawn praise here on BHT, came close to getting one of their songs into Director’s Cut. The crowdfunding perks included some creative opportunities to be involved in the production. Tomorrow will be a nice day for a “White Wedding” and dancing with yourself as Billy Idol headlines Taste Of Chicago at Grant Park’s Petrillo Band Shell. Idol’s opening act, the Chicago-based and extremely good David Bowie tribute band Sons Of The Silent Age, kick things off at 4:30 PM. The Isley Brothers and Sheila E. will perform at The Taste on Sunday. This weekend’s main concerts at Milwaukee’s SummerFest are Neil Finn and Chris Isaak (separately) tomorrow; and Sting and Peter Gabriel together on Sunday. The Millennium Art Festival takes place tomorrow and Sunday on Michigan Avenue and Lake Street. Be sure to take in some culture before heading off to Taste Of Chicago. England’s always imaginative indie label Fruits de Mer Records recently released a new batch of limited-run colored vinyl seven-inch interpretations of vintage material. German band Vibravoid covers Iron Butterfly’s “In-A-Gadda-Da-Vida” in two parts on one of the new records; California-based Sidewalk Society covers two David Bowie songs and two by The Action on another; and The Fruits de Mer Records Guide To The Hitchhikers Guide To The Galaxy features Australasia, Icarus Peel, and Blue Giant Zeta Puppies. The Powerpop Showcase coming to Subterranean on North Avenue next Thursday, July 14 will include performances by Mooner, Twins, and Arts And Letters. Graham Crackers Comics is having a Doctor Who Day Signing at its downtown location tomorrow from noon to 3:00 PM. Fans will have a chance to meet artists Andrew Pepoy and Jason Millet. The Square Roots festival is taking place this weekend on Lincoln Avenue between Montrose and Wilson. Lydia Loveless, Cracker, and Dolly Varden are among the music acts scheduled, and there will be craft beer, dance lessons, and a kid zone. According to Chicago Tribune media columnist Robert Feder, WXRT air personality Terri Hemmert’s weekly Breakfast With The Beatles program will not go missing while she takes a month off to recover from back surgery. Hemmert, who hopefully will be well enough for her annual master of ceremonies gig at Fest For Beatles Fans - Chicago in August, recorded some episodes of Breakfast before her surgery. Drazin’s Destiny. Piano accompanist and former member of the Famous In The Future comedy group David Drazin will be providing a live soundtrack to the classic Fritz Lang silent film Destiny next Saturday at 3:00 p.m. at the Gene Siskel Film Center. Chicago-based quartet Wired Minds have a release party coming up on July 23 at Schubas for their second EP The Death Of The Fear. “Listening,” the first single, is an impressive techno/guitar-driven tune with emotive vocals. I was happy to see Chicago’s reluctant celebrity The Walking Man downtown yesterday with a faint but gracious smile on his face. He’s apparently recovered enough from a recent attack to get back to doing what he does best. Contrary to speculation following his being hospitalized, The Walking Man did not lose his eyesight. Colman Gota - Tape Vocalist-bassist Colman Gota from the Madrid-based power pop band Insanity Wave creates edgy pop tunes reminiscent of Elvis Costello and Graham Parker on his second solo effort Tape. The 11 tracks were recorded with Mitch Easter of Let’s Active fame and multi-instrumentalist John Pfiffner at the same Fidelitorium Studios in North Carolina where Easter produced Insanity Wave’s third album back in 2000. Gota exudes an independent spirit and an urge to make the most of life throughout Tape, while delivering songs with an emphasis on guitar and organ that underscore his fascination for vintage indie rock. “Time keeps on ticking down and all you’ve done is run around,” Gota sings on “Another Chance,” while on “Do What I Want,” a tale of breaking free from a mundane nine-to-five job, he asks, “Whatever happened to the rebel inside?” The energetic “Waiting For A Chance” and the Motown flavored “Something I Don’t Need” likewise put biting lyrics to a steady beat. As a change of pace, “A Long Week Ahead” is a touching show of support set to a strings and acoustic guitar arrangement. “Back In Time,” a catchy song about traveling into the past to prevent mistakes that scuttled a relationship, could have sprung from one of Tom Petty’s early albums. “Sing Your Song” is an inside look at the music business, while “Tape” honors the cassettes that first introduced Gota to the music he’s loved ever since. “Plenty of good stuff on both sides,” he sings, and the song’s swaggering classic rock arrangement emphasizes the point. Book Learnin’ Happy 4th of July. On this great American holiday, let’s consider the great American novel. During the leisurely summer months, people often find extra time to read a book on the beach, or actually write one. If you’re among the latter group, you could benefit from some advice from self-published author Susan Kaye Quinn. She’s a former rocket scientist who launches sci-fi series at an accelerated pace (involving over 50 books so far) and knows quite a bit about marketing them. Quinn is a member of the SCBWI (Society of Children’s Book Writers and Illustrators) group I’ve belonged to for a number of years. She’ll be conducting a free workshop titled Series and Serials – Writing Stories That Keep Your Readers Coming Back For More through that group on Wednesday, July 20 at the Barnes and Noble store in Schaumburg. The workshop will focus on how to expand the structure of a story over the course of a trilogy, five-part-series, or nine-part serial. Those in attendance are encouraged to take notes and ask questions. Her presentation at Barnes and Noble is sure to be beneficial for aspiring as well as published writers. You can also find pages of essential tips in Quinn’s Indie Author Survival Guide, which is now in its second edition, and For Love Or Money - Crafting An Indie Author Career. Both books, along with Quinn’s popular novels in the Mindjack, The Royals Of Dharia, and Singularity series, are available on Amazon. Her short stories, often related to her serials, have appeared in sci-fi anthologies. Susan Kaye Quinn is not the only published writer in our group. Kym Brunner, Cherie Colyer, Mike Kelley, Marian Manseau, Terri Murphy, and Katie Sparks all have books on the market. Veronica Rundell’s literary agent is currently pitching Rundell’s YA novel to publishers. I’m honored to be part of this collection of talented people and have benefitted tremendously from their advice. Slumgulllion Cheap Trick will be at SummerFest in Milwaukee on July 7. Best wishes for a full recovery to WXRT air personality Terri Hemmert, who’ll be taking about a month off due to back surgery. Frank E. Lee, who retired from the station, will be filling in for Hemmert while she’s away. The Roots and Donnie Trumpet will kick off Taste Of Chicago 2016 on Wednesday, July 6 with a concert at the Petrillo Music Shell. Other acts scheduled to perform through July 10 include Kongos, Elle King, and Transviolet on Thursday; The Decemberists and Shakey Graves in a WXRT show on Friday; Billy Idol and the Chicago-based David Bowie tribute band Sons Of The Silent Age on Saturday; and The Isley Brothers and Sheila E. on Sunday. The Old Town, Wells Street, and Gold Coast art fairs have already taken place, but Chicagoans can still catch some paintings, photographs, and sculptures outdoors at The Millennium Art Festival, which takes place next Friday through Sunday on Lake Street at Michigan Avenue. Unfortunately, Artfest Michigan Avenue, which was scheduled for July 15 – 17, will not be held this year due to the construction of the new Apple Store. Checking out the Millennium Art Festival on Saturday before seeing to Sons Of The Silent Age at Taste Of Chicago would be an art/music mashup that would do the Thin White Duke proud. Milwaukee’s annual SummerFest, which is like Taste Of Chicago, except with 15,000 more musical acts, continues through July 10, with a day off on the 4th of July. Upcoming shows include Bodeans on July 3; Garbage on July 6; Cheap Trick on July 7; Paul McCartney on July 8; Neil Finn on July 9; Chris Isaak on July 9; and Sting and Peter Gabriel on July 10. The Telepaths, Lifecoach, and Steven Gilpin are performing at the Rock And Roll Firworks! show at Phyllis’ Musical Inn tomorrow night. On Monday, the venue will be hosting its 30th Anniversary All-Star Jam from noon to midnight, with over 10 bands scheduled to rock throughout the day. The triple bill of Rick Springield, Loverboy, and The Romantics will perform as part of the Grand Victoria’s Concert Series in Elgin this Sunday night. Comedian/magician and now screenwriter Penn Jillette and director Adam Rifkin will be at The Gene Siskel Film Center next Thursday, July 7 for the Chicago premiere of their new comedy Director’s Cut. The film also stars Herbert Blount and Missi Pyle. The official trailer for director Ron Howard’s new documentary Eight Days A Week: The Touring Years can now be seen on the Slate website. It’s less than a minute long, but is still generating a lot of interest. According to Slate writer Marissa Martinelli, the film will include previously unseen footage of The Beatles performing live from 1962 through 1966. It’s set to be released worldwide in September. Graham Crackers Comics is having a Doctor Who Day Signing at its downtown location next Saturday, July 9 from noon to 3:00 PM. Fans will have a chance to meet artists Andrew Pepoy and Jason Millet. Square Roots, a festival being staged on Lincoln Avenue between Montrose and Wilson next weekend, will feature live entertainment, craft beer, dance lessons, and a kid zone. Acts scheduled to perform include Lydia Loveles, Cracker, and Dolly Varden. If next Saturday’s Peter Gabriel and Sting concert at the United Center follows the same format as their recent shows in other cities, fans can expect to see these two popular musicians performing a number of songs together, in addition to each performing on his own. Cliff Johnson and The Raine will be sharing another bill with Kevin Lee & The Kings on Saturday, July 9 at FitzGeralds in Berwyn. The Powerpop Showcase is coming July 14 to Subterranean on North Avenue in Chicago and will feature performances by Mooner, Twins, and Arts And Letters. Metropolly, a band that has taken part in a number of Halloweekend Tribute shows over the years, will be performing an acoustic set at the Fetching Market in Munster, IN next Saturday, from 10 a.m. to noon. The city of Lockport, IL has a bunch of offbeat and entertaining things coming this summer under the banner of Great Midwestern Ballyhoo. A gentleman in a very steampunk outfit was handing out flyers at C2E2 in April advertising events such as Comicopolis, Z.A.P. Movie premiere, and a steampunk weekend. Fruits de Mer Records Guide To The Hitchhiker’s Gu...	cc/2019-30/en_head_0044.json.gz/line3475
__label__cc	0.626413	0.373587	« Heavy storms and floods have closed the visitors’ road, and wildlife has thrived because rangers kept it closed Elephants : Killing for Cash » Gurney’s Pitta – On the verge of extinction Saturday, September 26, 2009posted by admin 7:11 PM The Gurney’s Pitta – Thailand’s rarest bird Gurney’s Pitta in Khao Phra Bang Khram The dark morning stillness of thick lowland rainforest of Khao Nor Chuchi, Krabi province, is broken by thumping footsteps as two humans move slowly down the trail. We carry heavy photographic equipment to a photo-blind set the previous evening, deep in the jungle. Precipitation is heavy as I set up in the hide. My helper departs quickly, conveying the message to the wildlife in the area that the intruders have left. The ‘Emerald Pool in Khao Phra Bang Khram Animals of the night fade into their homes and the ecosystem enters its daylight cycle. As morning light awakens the rainforest, sounds of dripping moisture begin to subside while forest birds and insects start their incessant calls as they have for millions of years. Well hidden in the blind, I settle down, ever-vigilant for any movement on the forest floor. As the sun arches into the sky, light filters through the forest canopy in patches, illuminating the surroundings. There is a movement near the trail and a Hooded Pitta, common to this forest, hops about looking for food. The striking little blue-green bird with dark brown crown moves closer to the blind seemingly unconcerned about the looming structure. Gurney’s pitta male Snapping a few shots of the feathered creature but not wanting to alarm the other inhabitants of the forest, I continue to sit quietly hoping the spirits of the forest will answer my wish. A morning rain shower passes by but quickly dissipates. As if on cue, a small black and yellow bird magically appears in front of the photo-blind, catching my eye. It’s the creature I’ve been waiting for: the Gurney’s Pitta! The little bird, perhaps sensing danger, quickly disappears into the darkness of the jungle but within minutes, is back again just long enough for only one shot with the camera. The chance to see and photograph the Gurney’s Pitta, one of the rarest species in the world, has been my goal for several years. And this particular forest is the last known habitat for the bird which is both Thailand ‘s most endangered and a flagship species for the conservation of southern Thailand ‘s lowland rainforest. Gurney’s pitta female Gurney’s Pitta (Pitta gurneyi), or sometimes-called Black-breasted Pitta, is a small terrestrial forest bird endemic to Thailand and Burma . The male, with golden brown wings, bright yellow upper breast and flanks, black head and lower breast, white throat and brilliant iridescent blue crown and tail feathers, is striking indeed. The female is less colourful but, nevertheless, also very beautiful. The species nests in spiny under-story palms laying three to four eggs but usually fledging at most two or three young. They hop about the forest floor and eat mainly insects and earthworms found amongst leaf litter but also take snails and little frogs. Banded Pitta male Extremely secretive, they keep as much jungle between themselves and any intruders. When danger approaches, they hop into the underbrush and disappear. Of the world’s 31 known pittas, found from Africa to the Solomon Islands , and from Japan through Southeast Asia to New Guinea and Australia , 12 species are found in Thailand . They are Gurney’s, Giant, Banded, Hooded, Blue-winged, Blue, Blue-rumped, Eared, Mangrove, Garnet, Rusty-naped and Bar-bellied, of which the first five mentioned are found at Khao Nor Chuchi. The probable geographic origin of the Family Pittidae is in the Indo-Malayan region. Banded Pitta female Gurneys Pitta was first discovered in 1875 by W. Davison, a wildlife specimen collector working in Southern Burma for Allan Octavian Hume, a British civil servant working in India , and doyen of ornithology at that time. The bird was named after Humes friend, J.H. Gurney of the English county of Norfolk , and a fellow of the Zoological Society of London. In the early 20th century, the bird was actually considered common in southern Thailand . Around the 1980s, it was thought to be extinct after no reported sightings had taken place for at least three decades. Then, in 1986, Philip Round, Thailand ‘s top birder, rediscovered the Gurney’s Pitta at Khao Nor Chuchi. It was big news for bird conservation groups and was heard around the world. Historically, the world range of Gurney’s Pitta was a small concentrated area of lowland semi-evergreen forest along the coast and inland areas of the Thai peninsula, in the provinces of Trang, Krabi, Nakhon Si Thammarat, Surat Thani and Chumphon and Prachuap Khiri Khan. However, the once magnificent lowland tropical forest, its diversity of flora and fauna unsurpassed, has disappeared from most of those areas, due to man’s incessant greed, and his urge to destroy natural forest for the sake of agriculture and profit. Khao Nor Chuchi, at Khao Pra-Bang Khram Wildlife Sanctuary, Khlong Thom district, Krabi, about 56 kilometres southeast of the provincial capital, is the last known site for Gurney’s Pitta in Thailand . Khao Pra-Bang Khram, with its headquarters at Ban Bang Tieo village, was established as a non-hunting area in 1987 by the Royal Forest Department (RFD), at the behest of Bangkok Bird Club (now Bird Conservation Society of Thailand-BCST), specifically in order to protect Gurney’s Pitta. It was upgraded to a wildlife sanctuary in 1993, with a total area of 183 square kilometres. The Emerald Pool (Sa Morakot) within Khao Pra-Bang Khram Wildlife Sanctuary is a beauty spot visited by many local and foreign tourists. There are many trails open to nature explorers and bird watchers known as Thung Tieo Nature Trail Network. At least 318 different bird species have been recorded here. The site’s alternative name, Khao Nor Chuchi, comes from the 650-metre-high conical mountain which overlooks the area. Bird photographers also come to Khao Nor Chuchi after images of the Gurney’s. Many people, after travelling thousands of kilometres from different parts of the world, have left very disappointed after not seeing or photographing it. Gurney’s Pitta is a tough bird even to see, let alone photograph. Although the species once occupied about 40 square kilometres of this area, most of the extreme lowlands where they live and breed were excluded from the sanctuary. As a result, forest is still being destroyed to grow rubber, oil palm and coffee, and human settlement has taken up most of the area. Villagers still engage in poaching of animal and forest products from the reserved forest. On the day I photograph this Gurney’s Pitta, I still heard a gunshot. Pitta numbers at Khao Nor Chuchi have declined drastically in the last two decades from an estimated 40 pairs in 1986, down to 21 pairs in 1992. This slide was due primarily to uncontrolled forest destruction, perhaps abetted by capture of the species for the black market trade in forest birds, and even for some government-run zoos. According to BirdLife International’s Red Data there were only 11 breeding pairs and two extra males remaining in mid-2000. This year, only four to five nests have been found and sightings of individual birds have been minimal. At one nest that was abandoned, local birdwatchers found bird-nets put there by villagers who used the nets to capture the birds. The species was also found along the coast and inland at the most southern tip of Burma but no reports of them have come from there since about 1914 and it is anybody’s guess whether it still survives. No surveys can be done due to inaccessibility of the area and danger of land mines. Tough government regulations have also kept most researchers away from the area. BirdLife International, BirdLife Denmark , and NGOs such as BCST and the Oriental Bird Club have implemented a number of projects at Khao Nor Chuchi, in collaboration with RFDs Wildlife Conservation Division. However, these have slowed, but not halted, new settlements and further forest clearance. Ultimately, unless the wildlife sanctuary can be expanded to encompass all remaining lowland forest, and previously cleared areas reforested, Gurney’s Pitta faces a very bleak outlook for survival. This magnificent bird could disappear before we know it and that would be a sad day for conservation in Thailand . With just 11 breeding pairs left, the Gurney’s Pitta is very likely to be the first species to go extinct in this millennium, unless all parties concerned join hands in protecting it. On the day this male bird was photographed, a gunshot was heard. Tags: endangered, Gurney's Pitta, Hooded Pitta, Krabi, rare, Thailand This entry was posted on Saturday, September 26th, 2009 at 7:11 pm and is filed under The South. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.	cc/2019-30/en_head_0044.json.gz/line3476
__label__cc	0.648785	0.351215	Tag: PLX4032 Mutations in result in several distinct diseases including autosomal dominant limb-girdle Mutations in result in several distinct diseases including autosomal dominant limb-girdle muscular dystrophy (LGMD1B) (missense mutations that impair the function of the protein (often in a dominant-negative fashion) (= 0. 0.001) and myocardial performance index (MPI) (< 0.05). These data indicate that rapamycin improves cardiac function in mice lacking A-type lamins. Fig. 2 Treatment of < 0.05), and they did not reach the same maximum velocity as < PLX4032 0.01) (Fig. 2C). Latency to fall off the rotating PLX4032 rod was significantly longer in < 0.05). In addition, rapamycin-fed < 0.01) (Fig. 2C). Because = 0.0013, both groups = 23) (Fig. 3A). Rapamycin feeding resulted in a 35% increase in median life span (62 days versus 46 days) and a 23% increase in mean life span (62 days versus 50 days). Maximum life span was also increased by rapamycin treatment: Of the < 0.05). Survival was significantly increased in both male = 0.007) and female = 0.04) (fig. S2, A and B). Analysis of weekly body weights of the mice during treatment revealed that male and female < 0.05 and = 0.006, respectively), although individual values at specific time points were not significantly different after a Bonferroni post hoc test (fig. S2, C and D). To determine whether a higher dose of rapamycin would result in a larger increase in survival, we administered rapamycin (8 mg/kg) by intraperitoneal injection PLX4032 every other time starting at four weeks old. The bigger dose of rapamycin increased the survival of < 0 also.0001, both groupings = 11) (Fig. 3B), leading to a 57% upsurge in mean life time (81 times versus 51.5 times) and a 56% PLX4032 upsurge in median life time (85 times versus 54.5 times). Maximum life time of < 0.01). Fig. 3 Treatment of = 23) or diet plan that included encapsulated rapamycin (= 23). Success ... Provided the potential of rapamycin being a healing agent, we performed other life span research. Because rapamycin administration continues to be Rabbit Polyclonal to DQX1. associated with unwanted effects, we searched for to determine whether administration of much less rapamycin could have equivalent effects on durability. First, we decreased the regularity of administration of rapamycin (8 mg/kg) to once every week. Under these circumstances, the median and mean life spans were increased by 52.7 and 43.1%, respectively (< 0.0001) (fig. S3A). We also examined a short 1-week administration (three dosages every other time) of rapamycin beginning at four weeks old. Even this short rapamycin treatment was enough to significantly expand life time (fig. S3B), albeit to a smaller degree. These research indicate the fact that beneficial ramifications of rapamycin could be discovered rapidly after medication administration and take place even with much less regular administration. Finally, we implemented rapamycin (8 mg/kg) to = 0.0002, both groupings = 11) (fig. S3C), producing a 56% upsurge in mean life time (58 times versus 37 times) and a 60.5% upsurge in median life time (61 times versus 38 times). Although the utmost life span of = 0.035). To further understand the effects of rapamycin around the heart and muscle mass of = 0.00001), S6 kinase(T389) (= 0.02), and rpS6(S235/S236) (= 0.03) in = 0.07), consistent with previous in vivo evidence suggesting that rapamycin has stronger effects on S6 kinase phosphorylation than on 4E-BP1 phosphorylation (= 0.02) (Fig. 4C). In contrast, dietary rapamycin did not significantly decrease mTORC1 signaling in skeletal muscle mass (Fig. 4B). Phosphorylation of mTOR(S2448), S6 kinase(T389), rpS6(S235/S236), and 4E-BP1(S65) was unchanged in skeletal muscle mass from rapamycin-fed = 0.4, 0.6, 0.2, and 0.5, respectively). However, after 1 week of rapamycin injections (8 mg/kg, every other day), phosphorylation of S6 was significantly inhibited in both heart and skeletal muscles, indicating that a higher dose is necessary for detection of a decrease in signaling through the mTORC1 pathway in skeletal muscle mass (Fig. 4, D and E). Fig. 4 Signaling through the mTORC1 pathway in heart and muscle mass of = 0.042 and 0.012) (Fig. 5A). We also looked at desmin staining in tissue by immunohistochemistry and found that rapamycin diminished the number of myocytes made up of abnormal desmin conglomerates in skeletal muscle mass (Fig. 5B) but not in the cardiac tissue of = 0.025 and 0.68) (Fig. 5C). The differences in the effect of rapamycin in cardiac tissue by the two assays suggest that, although the number of cardiomyocytes made up of desmin conglomerates did not change, the total amount of desmin present in the tissue was reduced. Last, we examined whether rapamycin rescued the aberrant cross-sectional area of = 0.071) (fig. S4). Fig. 5 Rapamycin reduces abnormal desmin accumulation in = 6) compared to control-fed = ... Because autophagy is usually implicated in mouse models of desmin-related cardiomyopathies (= 0.0099) but not in heart (Fig. 6, A and B). Consistent with the increase in these autophagic markers, we also observed instances of the presence of autophagosomes. Author Randy MontgomeryPosted on June 19, 2017 Categories MainTags PLX4032, Rabbit Polyclonal to DQX1.	cc/2019-30/en_head_0044.json.gz/line3477
__label__cc	0.66749	0.33251	Student Handbook > Student Rights and Responsibilities > Network Usage Guidelines The following guidelines are of a general nature and clarify the Computer and Network Policy. The guidelines address common situations but are not meant to be exhaustive. Questions about acceptable use of Berea College computing and network resources should be directed to the Information Systems and Services department. Computer and Network Policy applies to all users and usage of College owned computers and data and voice networks. The policy applies apply to all host computer systems, personal computers, software, data sets, and other resources which may be accessed by users of the Berea College data or voice communications network All network users, including Berea College faculty, staff, students or contractors or other parties are expected to comply as was agreed by their signature on the application for a network/e-mail account. By logging in to the network, a user consents to these guidelines and all other IS&S policies and procedures implemented under the Computer and Network Policy. Limited personal use of computer and network resources is allowed, but priority is given to usage for College business and academic pursuits. Users of the Berea College data or voice network may access the Internet or make phone calls for personal purposes but the College is not responsible for the security and privacy of data or messages transmitted for such purposes. The College does not guarantee availability, reliability or capacity of Internet or voice connection for personal usage. Users may store a limited amount of personal data and documents not related to their work or study on a personal computer. If storage is overloaded, users may be asked to remove such personal data and documents. Users assume full responsibility for the legality of any personal data and documents stored. Users are cautioned that Internet surfing, the display of videos or the use of audio materials on a personal computer during work time is likely to distract from efficient work and may be outside the bounds of their department’s acceptable practices. Users of computer and network resources will abide by community decency standards, copyright restrictions and other legal requirements. Users may not utilize e-mail mailing lists, classified ads or other mass communications resources to advertise or sell regulated goods such as pharmaceuticals or firearms. Users may not utilize e-mail mailing lists, classified ads or other mass communications resources to harass, belittle or coerce other individuals or classes of persons. Users may not utilize e-mail, phone calls or other communications resources to harass or coerce another individual. Users may not utilize peer-to-peer upload/download software or services to obtain or distribute copyrighted material not specifically authorized to the service. Users may not modify the campus network wiring or configuration. Network hubs, switches or wireless routers may not be added to an existing port. Personal computers may not be configured to serve as routers or gateways to other networks, internal or external to Berea College. Network names of computers, printers and other network attached devices may not be changed. Network wires may not be cut, spliced or moved from their installed location. Users may not engage in activities which degrade network performance or which interfere with other users’ access to computer and network resources. Intentional spreading or creation of computer viruses is prohibited. Overloading network services by using hacking tools, e-mail spamming or other means are prohibited. Overloading network storage areas with personal or unnecessary data is prohibited. Initiation or propagation of e-mail chain letters is prohibited. Users may not attempt to circumvent system security or information protection mechanisms. Use of hacking techniques to uncover security loopholes or to circumvent network security and gain access to folders, databases, hardware, or other material on the network to which one is not authorized is will not be tolerated. Any network user found to have hacking software or paraphernalia installed on a computer connected to the campus data network will face immediate suspension of network access privileges and may be subject to further disciplinary action. Any attempt to guess other user’s passwords, access codes or encryption keys is forbidden. Users must respect institutional data confidentiality and others’ privacy. Unauthorized monitoring of electronic communications is forbidden. Attempts to gain unauthorized access to private information will be treated as violations of privacy, even if the information is publicly available through authorized means. Searching through directories to find unprotected information is a violation. Special access to information or other special computing privileges are to be used in performance of official duties only. Information obtained through special privileges is to be treated as confidential. As it relates to sensitive college data maintained on college-owned computers the following applies: Computers/Laptops: IS&S is responsible for the disposal of all College-owned computers, laptops and similar devices. Drives on these computers are wiped to DoD-3 standard before the unit is sold or sent to recycling. CD’s/DVD’s: Standard practice is to shred CD’s and DVD’s using standard paper shredders with built in capacity to shred this media. IS&S maintains such a shredder for this purpose. External Hard Drives: External hard drives including USB drives should be wiped to DoD-3 standards before disposal. Free software is available to do this such as CCleaner at http://www.piriform.com/ccleaner. Users are responsible for all actions initiated from their login ID(s). Each user is assigned a personal login ID with a unique name associated with their College student or employee records. Users should not share access to their personal login ID with others. In some situations, a user may also be issued a non-standard ID which can be used on specific computers for a particular function. The owner of a non-standard ID may share that ID with others, but he or she is responsible for all activity that occurs in sessions logged in under that ID. Passwords must be chosen in such a way that they cannot be easily guessed. Network software will enforce a minimum level of password complexity. Workstations should be logged off or locked when left unattended. Users may set up network sharing on a personal computer issued for their use in order to provide other users access to data or other resources. However, individuals are responsible for the content and legality of any information they choose to share. Users should avoid storing on paper on in computer files their passwords or other information that could be used to gain access to other campus computing resources. Network storage is provided to each individual user and to many groups such as employees in a department or students enrolled in a class. Network storage may be used only to store material associated with a user’s work or study. Network software will enforce storage size limits on network storage resources. Users are responsible for managing their stored data and documents within these size restrictions. Users must comply with software licensing terms. Software licensed to Berea College may not be installed on a computer not owned by Berea College. Personal computer users may not install copyright protected software not licensed to the College on a College owned computer. Personal computer users may install public domain or open source software on their computer, but are cautioned that installing such software may disrupt the efficient operation of the computer. If the computer requires service such software may be removed. Access to network resources is provided only to those officially associated with Berea College. Withdrawn student accounts and stored data and documents will be deleted immediately upon receipt by IS&S of official notification of the change in status. Graduated student accounts and stored data and documents will be deleted between two and four weeks after their graduation. Faculty, staff or contractor accounts will be disabled or deleted when a user ceases official association with Berea College. All data and documents stored on personal computers or personal network folders will be deleted or copied to another location at the discretion of the departing individual’s supervisor. When faculty, staff or contractors are assigned a new position and/or responsibilities within Berea College, access associated with the former position will be revoked and access associated with the new position must be requested. No services will be provided to outside organizations or agencies that would normally be provided by other public or private agencies within the geographical areas of the campus without the prior approval of the campus president or authorized vice president designee. Information Systems and Services manages all network resources. Only Information Systems and Services personnel or those authorized by the Chief Information Officer may be given physical access to College network servers, switches, routers and other equipment. Individual departments may operate a server connected to the campus network only with explicit permission from Information Systems and Services. Application for such permission is by letter to the Chief Information Officer. An application letter needs to include the need, use, and information content of the server and needs to identify a Berea College faculty or staff member who will be ultimately responsible for the use, maintenance and content of the server. IS&S system administrators may access user’s files for the maintenance of networks and computer and storage systems (e.g., to create backup copies of data). IS&S system administrators will not intentionally inspect the contents of data files or e-mail messages or disclose such contents to any person other than the owner, sender, or an intended recipient without the consent of the owner, sender, or an intended recipient unless required to do so by law or to investigate complaints regarding files or documents alleged to contain material contrary to Berea College policies or applicable laws.	cc/2019-30/en_head_0044.json.gz/line3478
__label__wiki	0.562191	0.562191	Home / compendium decisions / Supreme Court of the Republic of the Phi... Supreme Court of the Republic of the Philippines, International School Alliance of Educators v. Hon Leonardo A. Quisumbing and others, 1 June 2000, G.R. No. 128845 Constitution of the Republic of the Philippines Article II, Section 2 The Philippines renounces war as an instrument of national policy, adopts the generally accepted principles of international law as part of the law of the land and adheres to the policy of peace, equality, justice, freedom, cooperation, and amity with all nations. Ratified treaties;1 Instruments not subject to ratification2 Discrimination on the grounds of nationality/ Discrimination between local and foreign workers/ Action for discrimination/ Reference to international law to strengthen a decision based on domestic law An international school in the Philippines employed both local and foreign workers, the latter being paid higher wages and also receiving other benefits. The Filipino employees instituted legal proceedings arguing that there was discrimination. The Court held that the provisions granting foreign employees higher wages and other benefits were unconstitutional and proceeded to rely on international law to add force to its case: “International law, which springs from general principles of law, likewise prescribes discrimination. General principles of law include principles of equity, i.e. the general principles of fairness and justice, based on the test of what is reasonable. The Universal Declaration of Human Rights, the International Covenant on Economic, Social and Cultural Rights, the International Convention on the Elimination of All Forms of Racial Discrimination, the Convention against Discrimination in Education, the Convention (No. 111) Concerning Discrimination in Respect of Employment and Occupation – all embody the general principle against discrimination, the very antithesis of fairness and justice. The Philippines, through its Constitution, has incorporated this principle as part of its national laws.” The Court subsequently examined the provisions of these various international instruments in greater detail: “Notably, the International covenant on Economic, Social and Cultural Rights, supra, in Article 7 thereof, provides: “The States Parties to the present Covenant recognize the right of everyone to the enjoyment of just and favorable conditions of work, which ensure, in particular: a) Remuneration which provides all workers, as a minimum, with: Fair wages and equal remuneration for work of equal value without distinction of any kind, in particular women being guaranteed conditions of work not inferior to those enjoyed by men, with equal pay for equal work.” The foregoing provisions impregnably institutionalize in this jurisdiction the long-honored legal truism of “equal pay for equal work”. Persons who work with substantially equal qualifications, skill, effort and responsibility, under similar conditions, should be paid similar salaries. This rule applies to the School, its “international character” notwithstanding.” After relying on national law, the Supreme Court of the Philippines referred to international instruments to point to the fundamental nature of the equal pay principle. The Court found in this instance that the differences in treatment between Filipino and foreign employees were discriminatory but that the foreign workers could continue to enjoy the benefits relating to their nationality such as the payment of their removal expenses, etc. 1 ILO Discrimination (Employment and Occupation) Convention, 1958 (No. 111); International Covenant on Economic, Social and Cultural Rights, 1966; International Convention on the Elimination of All Forms of Racial Discrimination, 1965; Convention against Discrimination in Education, 1960. 2 Universal Declaration of Human Rights, 1948.	cc/2019-30/en_head_0044.json.gz/line3480
__label__cc	0.685267	0.314733	Forum Clube Cetico » Foreign Languages » Tópico: Atheism is moral?! Prove it! Autor Tópico: Atheism is moral?! Prove it! (Lida 1581 vezes) 0 Membros e 1 Visitante estão vendo este tópico. Jeanioz Atheism is moral?! Prove it! « Online: 13 de Maio de 2008, 13:22:28 » Take this test: http://www.philosophersnet.com/games/morality_play.htm My result: Your Moral Parsimony Score is 55% Moral frameworks can be more or less parsimonious. That is to say, they can employ a wide range of principles, which vary in their application according to circumstances (less parsimonious) or they can employ a small range of principles which apply across a wide range of circumstances without modification (more parsimonious). An example might make this clear. Let's assume that we are committed to the principle that it is a good to reduce suffering. The test of moral parsimony is to see whether this principle is applied simply and without modification or qualification in a number of different circumstances. Supposing, for example, we find that in otherwise identical circumstances, the principle is applied differently if the suffering person is from a different country to our own. This suggests a lack of moral parsimony because a factor which could be taken to be morally irrelevant in an alternative moral framework is here taken to be morally relevant. How to interpret your score The higher your percentage score the more parsimonious your moral framework. In other words, a high score is suggestive of a moral framework that comprises a minimal number of moral principles that apply across a range of circumstances and acts. What is a high score? As a rule of thumb, any score above 75% should be considered indicative of a parsimonious moral framework. However, perhaps a better way to think about this is to see how your score compares to other people's scores. In fact, your score of 55% is slightly lower than the average score of 64%. This suggests that you have utilised a somewhat wider range of moral principles than average in order to make judgements about the scenarios presented in this test, and that you have, at least on occasion, judged aspects of the acts and circumstances depicted here to be morally relevant that other people consider to be morally irrelevant. Moral Parsimony - good or bad? We make no judgement about whether moral parsimony is a good or bad thing. Some people will think that on balance it is a good thing and that we should strive to minimise the number of moral principles that form our moral frameworks. Others will suspect that moral parsimony is likely to render moral frameworks simplistic and that an overly parsimonious moral framework will leave us unable to deal with the complexity of real circumstances and acts. We'll leave it up to you to decide who is right. How was your score calculated? Your score was calculated by combining and averaging your scores in the four categories that appear below. Geographical Distance This category has to do with the impact of geographical distance on the application of moral principles. The idea here is to determine whether moral principles are applied equally when dealing with sets of circumstances and acts that differ only in their geographical location in relation to the person making the judgement. Your score of 83% is somewhat higher than the average score of 72% in this category. And indeed, it is a high score, which suggests that geographical distance only plays a marginal role in your moral thinking. To the extent that it does play a role - even if only a marginal one - the parsimoniousness of your moral framework is reduced. Family Relatedness In this category, we look at the impact of family loyalty and ties on the way in which moral principles are applied. The idea here is to determine whether moral principles are applied without modification or qualification when you're dealing with sets of circumstances and acts that differ only in whether the participants are related through family ties to the person making the judgement. Your score of 51% is not greatly different to the average score of 52% in this category. But what is significant is that it is low enough to suggest that issues of family relatedness are a relevant factor in your moral thinking. Probably, you think that you have a slightly greater moral obligation towards people who are related to you than towards those who are not. If you do think that, then it decreases the parsimoniousness of your moral framework. Acts and Omissions This category has to do with whether there is a difference between the moral status of acting and omitting to act where the consequences are the same in both instances. Consider the following example. Let's assume that on the whole it is a bad thing if a person is poisoned whilst drinking a cola drink. One might then ask whether there is a moral difference between poisoning the coke, on the one hand (an act), and failing to prevent a person from drinking a coke someone else has poisoned, when in a position to do so, on the other (an omission). In this category then, the idea is to determine if moral principles are applied equally when you're dealing with sets of circumstances that differ only in whether the participants have acted or omitted to act. Your score of 35% is much lower than the average score of 61% in this category. This suggests that the difference between acting and omitting to act is a relevant factor in your moral framework. Usually, this will mean thinking that those who act have greater moral culpability than those who simply omit to act. To insist on a moral distinction between acting and omitting to act is to decrease the parsimoniousness of your moral framework. This category has to do with whether scale is a factor in making moral judgements. A simple example will make this clear. Consider a situation where it is possible to save ten lives by sacrificing one life. Is there a moral difference between this choice and one where the numbers of lives involved are different but proportional - for example, saving 100 lives by sacrificing ten? In this category then, the idea is to determine whether moral principles are applied without modification or qualification when you're dealing with sets of circumstances that differ only in their scale, as in the sense described above. Your score of 51% is significantly lower than the average score of 73% in this category. This suggests that scale, as it is described above, is an important consideration in your moral thinking. To insist on the moral significance of scale is to decrease the parsimoniousness of your moral framework. FxF Nível Máximo Yohohoho! Re: Atheism is moral?! Prove it! « Resposta #1 Online: 19 de Maio de 2008, 06:23:48 » Lento demais o servidor. Citação de: Ilovefoxes em 19 de Maio de 2008, 06:23:48 Buy a new computer and throw off this "Casas Bahia" one. In fact, your score of 84% is significantly higher than the average score of 64%. This suggests that you have utilised a noticeably smaller range of moral principles than average in order to make judgements about the scenarios presented in this test, and that you have tended to judge aspects of the acts and circumstances depicted here to be morally irrelevant that other people consider to be morally relevant. Your score of 100% is a lot higher than the average score of 52% in this category. It looks as if issues of family relatedness play have no significant role to play in your thinking about moral issues. Your score of 51% is a little lower than the average score of 61% in this category. This suggests that the distinction between acting and omitting to act is sometimes a relevant factor in your moral thinking. Probably, you tend to believe that those who act have a greater moral culpability than those who simply omit to act. If this is what you believe, it decreases the parsimoniousness of your moral framework. Your score of 100% is significantly higher than the average score of 73% in this category. It seems that scale, as it is described above, is not an important consideration in your moral worldview. But if, contrary to our findings, it is important, then it decreases the parsimoniousness of your moral framework. India and Australia In Question 13 you were asked the following: You see an advertisement from a charity in a newspaper about a person in severe need in Australia. You can help this person at little cost to yourself. Are you morally obliged to do so? However, fifty percent of people undertaking this activity are asked a slightly different question, where the country India is substituted for the country Australia. The idea is to determine what kind of impact "culural distance" has on the moral judgements that people make. The important point here is that the vast majority of people who visit this web site are from the United States, Canada and the United Kingdom. Consequently, in a comparison of the lives and lifestyles of TPM Online visitors, residents of India and residents of Australia, there will be bigger cultural differences between TPM Online visitors and residents of India than between TPM Online visitors and residents of Australia. Of course, whether a perception of cultural differences will enter into moral judgements, and if so, what its impact will be is entirely a matter of conjecture at this point. Indeed, whatever results we find here, they will only ever be suggestive of further avenues of enquiry. This aspect of the activity is simply not rigorous enough that it will be possible to draw definitive conclusions. It will nevertheless be interesting! * 26% of respondents who were asked about a person in severe need in Australia responded that they were stongly obliged to help compared to 25% who responded this way when asked about a person in severe need in India. * 43% of respondents who were asked about a person in severe need in Australia responded that they were weakly obliged to help. This is exactly the same as the percentage who responded this way when asked about a person living in India. * 31% of respondents who were asked about a person in severe need in Australia responded that they were not obliged to help compared to 32% who responded this way when asked about a person in severe need in India. Gigaview Mensagens: 14.893 Interesting, but the model could be improved using cross tabulation considering nationality, social, cultural and economic status. Brandolini's Bullshit Asymmetry Principle: "The amount of effort necessary to refute bullshit is an order of magnitude bigger than to produce it". Eremita Ecce. « Resposta #5 Online: 02 de Junho de 2008, 00:54:20 » I'll not copy'n'paste everything... but my Moral Parsimony Score is 84%. I don't care about geolocation, care for family, don't care any bull---- for scale, et cetera. Like Haldane, I would NOT give away my life for a bro' or a cousin... but for 2+ brothers or 8+ cousins, yes! Latebra optima insania est. Curve Clube Cetico Variation - SnowRaptor Página criada em 0.148 segundos com 25 procedimentos.	cc/2019-30/en_head_0044.json.gz/line3483
__label__cc	0.637026	0.362974	Summer Experience at the CSNE This summer I had the privilege of participating in the 10-week CSNE Research Experience for Undergraduates (REU) program as a UW Fellow. I joined 10 other “REUs” from around the country and eight Seattle-area high school students who were participating in the CSNE’s Young Scholars Program. Like me, they were all excited about getting involved in neural engineering research. Over the course of my research experience project, I learned some C++ programming language, created customized 3D-printed parts, and met many interesting and enthusiastic people. In RET program, teachers turn summers into science For middle and high school teachers, summers are a time to recharge after a long school year. It can be a rare chance to travel or spend quality time with friends and family. But for the past four years, a small group of Seattle-area educators have elected to spend their summers on the UW Seattle campus, conducting engineering research in a CSNE-affiliated lab and developing a curriculum unit to bring the principles of neural engineering to their students. Josh Hancock: Adaptive Outdoorsman When Josh Hancock moved to Seattle eight years ago, he envisioned a life outdoors, full of climbing, skiing, and hiking. Though he managed to live out that dream for seven years exploring the Pacific Northwest, his life changed dramatically on December 3, 2014, when an injury left him without motor control or sensory function below his waist. Study abroad with the CSNE Studying abroad isn’t just for undergraduates looking for a good time. Engineers, neuroscientists and others can study abroad in India or Germany, all while conducting cutting-edge research in neural engineering through two summer exchange programs offered by the CSNE. The first program provides opportunities for students at all CSNE core partner institutions (University of Washington, San Diego State University, Massachusetts Institute of Technology) and students at the BrainLinks-BrainTools Center of Excellence at the University of Freiburg (Germany). This exchange program, which was formed in 2014, sends students from the UW, MIT and SDSU to University of Freiburg labs during the summer. Students at the University of Freiburg can also travel to CSNE-affiliated labs in Seattle, Boston and San Diego to conduct research. Face the Music Wins Second CSNE Hackathon Happily sacrificing their weekend to science, fifteen students from four universities gathered in the CSNE in Seattle for the second annual Hackathon.	cc/2019-30/en_head_0044.json.gz/line3503
__label__wiki	0.584042	0.584042	GQ005 Nsork Highlands National Park Current view: summary Country/territory: Equatorial Guinea IBA Criteria met: A1, A2, A3 (2001) For more information about IBA criteria please click here Area: 70,000 ha Protection status: The Nsork (or Nsoc) Highlands are situated in the south-eastern corner of Río Muni and support one of the largest and best-preserved remaining areas of primary rainforest. The park is approximately triangular in shape and is bounded to the west by the Abang river, and to the south by the track linking the towns of Alum and Nsork. The north-eastern border is defined by the watershed between the Ouro river system to the north and the Abang and the Ncama rivers (the last flows through the eastern half of the park), affluents of the Ogooué river system to the south in Gabon. The park sits on a granitic plateau at about 500 m, from which a number of tall inselbergs protrude. The human population within the park is small, but probably exceeds 5,000 in the surrounding villages. Key biodiversity See Box and Tables 2 and 3 for key species. Nests of Picathartes oreas have been found and much habitat suitable for this species occurs. The site has, as yet, been extremely incompletely surveyed and it is expected that further work will reveal many more species of the Guinea–Congo Forests biome as well as, possibly, other restricted-range species of the Cameroon and Gabon lowlands EBA. Non-bird biodiversity: The flora is, as yet, practically unsurveyed. Threatened mammals include four primate species of global conservation concern; Colobus satanas (VU), Mandrillus sphinx (LR/nt), Gorilla gorilla (EN) and Pan troglodytes (EN). The elephant Loxodonta africana (EN) also occurs. BirdLife International (2019) Important Bird Areas factsheet: Nsork Highlands National Park. Downloaded from http://www.birdlife.org on 18/07/2019.	cc/2019-30/en_head_0044.json.gz/line3507
__label__wiki	0.800063	0.800063	Writings, video, audio by David Swanson War list Posted on December 10, 2014 by davidswanson Plutocrats for Peace: The Nobel-Carnegie Model “Dear Fredrik, Last Friday I went to an event organized by the Carnegie Corporation on the anniversary of the end of WWI. I was struck by how similar Andrew Carnegie’s ideas, as well as his philanthropy, were to Alfred Nobel’s. Do you know whether they were ever in contact? All best, Peter [Weiss]. “These are Peter’s questions: Why the similarities? Were Carnegie and Nobel ever in contact? And this is mine: Why is the connection so interesting – and consequential? –Fredrik S. Heffermehl.” The above was the announcement of a contest at NobelWill.org that I just won with the following: We do not know of, but also cannot exclude, a meeting face to face, or an exchange of letters, between Alfred Nobel and Andrew Carnegie that can explain how strikingly “similar Andrew Carnegie’s ideas, as well as his philanthropy, were to Alfred Nobel’s.” But the similarity is partially explained by the culture of the day. They were not the only tycoons to fund war abolition, just the wealthiest. It may be further explained by the fact that a primary influence on both of them in their peace philanthropy was the same person, a woman who met them both in person and was in fact very close friends with Nobel — Bertha von Suttner. Further, Nobel’s philanthropy came first and was itself an influence on Carnegie’s. Both offer fine examples for today’s super-rich — far richer, of course, than even Carnegie, but none of whom have put a dime into funding the elimination of war. They also offer excellent examples for the legally mandated operation of their own institutions which have strayed so far off course. Alfred Nobel (1833-1896) and Andrew Carnegie (1835-1919) lived in an era with fewer super-wealthy individuals than today; and even Carnegie’s wealth did not match that of today’s wealthiest. But they gave away a higher percentage of their wealth than today’s wealthy have done. Carnegie gave away a higher amount, adjusted for inflation, than all but three living Americans (Gates, Buffett, and Soros) have thus far given.* No one in the Forbes list of top 50 current philanthropists has funded an effort to abolish war. Nobel and Carnegie funded that project heavily while they lived, and engaged in promoting it apart from their financial contributions. Before they died, they arranged to leave behind them a legacy that would continue funding efforts to reduce and eliminate war from the world. Those legacies have done a great deal of good and have the potential to do a great deal more, and to succeed. But both have survived into an era that largely disbelieves in the possibility of peace, and both organizations have strayed far from their intended work, changing their missions to match the times, rather than resisting a militarization of culture by sticking to their legal and moral mandates. What is interesting and consequential about the similarities between Nobel and Carnegie is the extent to which their philanthropy for peace was a product of their time. Both became engaged in peace activism, but both favored the abolition of war before becoming so engaged. That opinion was more common in their age than now. Philanthropy for peace was also more common, though usually not with the same scale and consequence that Nobel and Carnegie managed. What is most interesting is that the consequences of what Nobel and Carnegie did remain to be determined, by the actions living people take to fulfill the promise of the Nobel Peace Prize and the Carnegie Endowment for International Peace, as well as by the actions we take to pursue the peace agenda outside of those institutions, and perhaps by current philanthropists who might find ways to emulate these past examples. In 2010, Warren Buffett and Bill and Melinda Gates encouraged billionaires to donate half their wealth (not up to the Nobel-Carnegie standard, but still significant). Buffett described the first 81 billionaires’ signatures on their pledge as “81 Gospels of Wealth,” in tribute to “The Gospel of Wealth,” an article and book by Carnegie. It would be hard to prove that Carnegie and Nobel never corresponded. We are dealing here with two prolific letter writers in an age of letter-writing, and two men whose letters we know have vanished from history in huge numbers. But I have read a number of biographical works of the two of them and of friends they had in common. Some of these books refer to both men in such a way that if the author knew them ever to have met or corresponded it certainly would have been mentioned. But this question may be a red herring. If Nobel and Carnegie came into contact with each other, it was clearly not extensive and certainly not what made them similar in attitudes toward peace and philanthropy. Nobel was a model for Carnegie, as his peace philanthropy preceded Carnegie’s in time. Both men were urged on by some of the same peace advocates, most importantly Bertha von Suttner. Both men were exceptional, but both lived in an era in which funding progress toward the elimination of warfare was something that was done, unlike today when it is something that just isn’t done — not even by the Nobel Committee or the Carnegie Endowment for International Peace. One could list a hundred similarities and dissimilarities between Nobel and Carnegie. Some of the similarities that might have a slight bearing here include these. Both men had immigrated in their youth, Nobel from Sweden to Russia at age 9, Carnegie from Scotland to the United States at age 12. Both were sickly. Both had little formal schooling (not as rare back then). Both were longtime bachelors, Nobel for life, and Carnegie into his 50s. Both were lifelong travelers, cosmopolitans, and (particularly Nobel) loners. Carnegie wrote travel books. Both were writers of numerous genres with a wide array of interests and knowledge. Nobel wrote poetry. Carnegie did journalism, and even happened to remark of the power of news reporting that “Dynamite is child’s play compared to the press.” Dynamite was of course one of Nobel’s inventions, and also a product someone once used to try to blow up Carnegie’s house (something one historian I asked pointed to as the closest connection between the two men). Both were in part but not primarily war profiteers. Both were complex, contradictory, and certainly to some extent guilt ridden. Nobel tried to rationalize his manufacture of weapons with the thought that extreme enough weapons would persuade people to abandon war (a somewhat common idea up through the age of nuclear nations waging and losing numerous wars). Carnegie used armed force to suppress workers’ rights, had got his break running telegraphs for the U.S. government during the U.S. Civil War, and profited from World War I. The argument that those who grow rich will know best what to do with their hoarded wealth is actually supported by the examples of Nobel and Carnegie, although they are in this regard — of course — exceptional cases rather than the rule. It is very hard to argue with the general thrust of what they did with their money, and the assignment that Carnegie left behind for his Endowment for Peace is something of a model of morality that puts any professor of ethics to shame. Carnegie’s money was to be spent on eliminating war, as the most evil institution in existence. But once war has been eliminated, the Endowment is to determine what the next most evil institution is, and begin working to eliminate that or to create the new institution that would do the most good. (Isn’t this what any ethical human being should be engaged in, whether paid for it or not?) Here’s the relevant passage: “When civilized nations enter into such treaties as named or war is discarded as disgraceful to civilized men, as personal war (dueling) and man selling and buying (slavery) have been discarded within the wide boundaries of our English-speaking race, the trustees will please then consider what is the next most degrading remaining evil or evils, whose banishment — or what new elevating element or elements if introduced or fostered, or both combined — would most advance the progress, elevation and happiness of man, and so on from century to century without end, my trustees of each age shall determine how they can best aid man in the upward march to higher and higher stages of developments unceasingly, for now we know that as a law of his being man was created with the desire and capacity for improvement to which, perchance, there may be no limit short of perfection even here in this life upon earth.” Here’s the key passage from the will of Alfred Nobel, which created five prizes including: “one part to the person who shall have done the most or the best work for fraternity between nations, for the abolition or reduction of standing armies and for the holding and promotion of peace congresses.” Both Nobel and Carnegie found their way to opposing war through the general culture around them. Nobel was a fan of Percy Bysshe Shelley. Carnegie’s notion quoted above of progress in overcoming slavery, dueling, and other evils — with war to be added to the list — could be found in early U.S. abolitionists (of slavery and war) like Charles Sumner. Carnegie was a 1898 anti-imperialist. Nobel first raised the idea of ending war to Bertha von Suttner, not the other way around. But it was the relentless advocacy of von Suttner and others that moved the two men to engage as they did in what was a very top-down, respectable, not to say aristocratic peace movement that advanced through the recruitment of VIPs and the holding of conferences with high-level government officials, as opposed to marches, demonstrations, or protests by anonymous masses. Bertha von Suttner persuaded first Nobel and then Carnegie to fund her, her allies, and the movement as a whole. Both Nobel and Carnegie viewed themselves as a bit heroic and viewed the world through that lens. Nobel established a prize for an individual leader, though it has not always been administered as intended (sometimes going to more than one person or to an organization). Carnegie similarly created a Hero Fund to fund, and to make the world aware of, heroes of peace, not war. Both men, as cited above, left formal instructions for the continued use of their money for peace. Both intended to leave a legacy to the world, not just to their personal families, of which Nobel didn’t have any. In both cases the instructions have been grossly disregarded. The Nobel Peace Prize, as well detailed in the writings of Fredrik Heffermehl, has been awarded to many who have not fit the requirements, including some who have even favored war. The Carnegie Endowment for International Peace has openly rejected its mission of eliminating war, moved on to numerous other projects, and re-categorized itself as a think tank. Of numerous individuals who reasonably might have been awarded a Nobel Peace Prize but have not been — a list that usually begins with Mohandas Gandhi — one nominee in 1913 was Andrew Carnegie, and the laureate in 1912 was Carnegie’s associate Elihu Root. Of course, mutual friend of Nobel and Carnegie, Bertha von Suttner received the prize in 1905 as did her associated Alfred Fried in 1911. Nicholas Murray Butler received the prize in 1931 for his work at the Carnegie Endowment, which included lobbying for the Kellogg-Briand Pact of 1928. Frank Kellogg got the prize in 1929, and Aristide Briand already had in 1926. When U.S. President Theodore Roosevelt received the prize in 1906 it was Andrew Carnegie who persuaded him to make the trip to Norway to accept it. There are numerous connections of this sort that all came after Nobel’s death. Bertha von Suttner, mother of the war abolition movement, became a major international figure with the publication of her novel Lay Down Your Arms in 1889. I don’t think it was false modesty but accurate assessment when she attributed the success of her book to a sentiment already spreading. “I think that when a book with a purpose is successful, this success does not depend on the effect it has on the spirit of the times but the other way around,” she said. In fact, both are certainly the case. Her book tapped into a growing sentiment and dramatically expanded it. The same can be said for the philanthropy (truly loving of people) of Nobel and Carnegie that she encouraged. But the best laid plans can fail. Bertha von Suttner opposed one of the first nominees for the peace prize, Henri Dunant as a “war alleviator,” and when he received it, she promoted the view that he’d been honored for supporting the abolition of war rather than for his work with the Red Cross. In 1905 1906, as noted, the prize went to warmonger Teddy Roosevelt, and the year after to Louis Renault, causing von Suttner to remark that “even war could get the prize.” Eventually people like Henry Kissinger and Barack Obama would make the list of laureates. A prize meant to fund demilitarization work was awarded in 2012 to the European Union, which could fund demilitarization most easily by spending less money on weaponry. It did not take long for Carnegie’s legacy to slip off track as well. In 1917 the Endowment for Peace backed U.S. involvement in World War I. After a second world war, the Endowment put leading warmonger John Foster Dulles on its board along with Dwight D. Eisenhower. The same institution that had backed the Kellogg-Briand Pact, which bans all war, backed the UN Charter which legalizes wars that are either defensive or UN-authorized. As the disregard of climate change in the 1970s and 1980s helped create today’s climate crisis, disregard of Nobel’s and Carnegie’s intentions and legal mandates in the early and mid-twentieth century helped create today’s world in which U.S. and NATO militarism are widely acceptable to those in power. Jessica T. Mathews, current President of the Carnegie Endowment for International Peace, writes: “The Carnegie Endowment for International Peace is the oldest international affairs think tank in the United States. Founded by Andrew Carnegie with a gift of $10 million, its charter was to ‘hasten the abolition of war, the foulest blot upon our civilization.’ While that goal was always unattainable, the Carnegie Endowment has remained faithful to the mission of promoting peaceful engagement.” That is, while denouncing without argument my required mission as impossible, I have remained faithful to that mission. No. It doesn’t work that way. Here’s Peter van den Dungen: “The peace movement was especially productive in the two decades preceding World War I when its agenda reached the highest levels of government as manifested, for instance, in the Hague Peace Conferences of 1899 and 1907. A direct result of these unprecedented conferences – which followed an appeal (1898) by Tsar Nicholas II to halt the arms race, and to substitute war by peaceful arbitration – was the construction of the Peace Palace which opened its doors in 1913, and which celebrated its centenary in August 2013. Since 1946, it is of course the seat of the International Court of Justice of the UN. The world owes the Peace Palace to the munificence of Andrew Carnegie, the Scottish-American steel tycoon who became a pioneer of modern philanthropy and who was also an ardent opponent of war. Like no one else, he liberally endowed institutions devoted to the pursuit of world peace, most of which still exist today. “Whereas the Peace Palace, which houses the International Court of Justice, guards its high mission to replace war by justice, Carnegie’s most generous legacy for peace, the Carnegie Endowment for International Peace (CEIP), has explicitly turned away from its founder’s belief in the abolition of war, thereby depriving the peace movement of much-needed resources. This could partly explain why that movement has not grown into a mass movement which can exert effective pressure on governments. I believe it is important to reflect on this for a moment. In 1910 Carnegie, who was America’s most famous peace activist, and the world’s richest man, endowed his peace foundation with $10 million. In today’s money, this is the equivalent of $3.5 billion. Imagine what the peace movement – that is, the movement for the abolition of war – could do today if it had access to that kind of money, or even a fraction of it. Unfortunately, while Carnegie favoured advocacy and activism, the trustees of his Peace Endowment favoured research. As early as 1916, in the middle of the First World War, one of the trustees even suggested that the name of the institution should be changed to Carnegie Endowment for International Justice.” I’m not sure any two economists calculate the value of inflation the same way. Whether $3.5 billion is the right number or not, it is orders of magnitude larger than anything funding peace today. And $10 million was only a fraction of what Carnegie put into peace through the funding of trusts, the building of buildings in DC and Costa Rica as well as the Hague, and the funding of individual activists and organizations for years and years. Imagining peace is difficult for some people, perhaps for all of us. Maybe imagining someone wealthy investing in peace would be a step in the right direction. Maybe it will help our thinking to know that it’s been done before. *By some calculations some of the early robber barons were, in fact, wealthier than some of our current ones. CategoriesUncategorized TagsPeace and War Previous PostPrevious Talk Nation Radio: Lia Tarachansky on How Israel Was Really Created in 1948 Next PostNext Elizabeth Warren Could Use Some Elizabeth Peacen Watch me speak to a peace group Watch me debate West Point's ethics professor on whether war can ever be justified More videos. Invite me to speak. Activist alerts. David Swanson news. World Beyond War news. Charlottesville news. 2019 Speaking Events Poulsbo, WA, Aug. 4. Seattle, WA, Aug. 4. Surrey, BC, Aug. 5. Vancouver, BC, Aug. 5. Chicago, IL, Aug. 27 Evansville, IN, Sep. 26 Milano, Italia, Oct. 3 Limerick, Ireland, Oct. 5-6 Find more events here. 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__label__cc	0.580148	0.419852	DAWSON Sponsors Veteran Art Exhibit of South Texas by DAWSON Editor \| Nov 9, 2018 \| News It started with a conversation over dinner this past spring in San Antonio, TX with a remarkable man who shared his story, retired U.S. Army Sgt. Mario Lopez. After the Sept 11th attacks, Mario joined the Army and was deployed to both Iraq and Afghanistan. During a mission in 2008, a 3-ton IED burned over 54% of his body, took his right arm (he was right-handed), his right eye, and four fingers on his left hand. During his recovery at the San Antonio Medical Center, Mario began painting, learning how to physically use his left arm, how to comprehensively view life through one eye, and how to communicate beauty through brokenness. Mario revealed, “My art is the action I take to give back to the human community, showing all that no matter what, life is worth living.” As he refined his art, Mario discovered a very talented local community of veteran artists. Mario had a vision to gather this talent for a “Veteran Art Exhibit”. DAWSON was honored to help bring the vision to life on Friday, November 2nd on campus at San Antonio A&M, who purchased one of the larger pieces by emerging artist, veteran, and mother, Brandi Hartigan. The military community is dear to DAWSON’s heart. We recognize and esteem their daily sacrifices. To name just a few: Mark Lee and his volunteer service with the Centurion Military Alliance (CMA) helps men, women, and spouses with the transition from military to civilian life; Wil Slora whose family faithfully serves at The Fisher House of South Texas year round; Alan Reynolds who has broken ground to serve the young families at Fort Sam Elementary School. It’s an unmitigated privilege to know and work alongside them. We wish all our veterans a very celebratory Nov 11th, Veteran’s Day!	cc/2019-30/en_head_0044.json.gz/line3509
__label__wiki	0.67659	0.67659	Kante rules out Real move as he still has Chelsea ‘aims’ N’Golo Kante still has “aims” he wishes to fulfil at Chelsea before he leaves. The midfielder has been linked with a move to Real Madrid... N’Golo Kante still has “aims” he wishes to fulfil at Chelsea before he leaves. The midfielder has been linked with a move to Real Madrid but, even after winning a Premier League title and FA Cup in two seasons at Stamford Bridge, he does not consider his work done. Some feel that Maurizio Sarri is trying to “phase out” Kante by changing his playing position, while others believe the Frenchman has been made to look “very average” by his manager’s demands. But Zidane seems unperturbed, and sees Kante as central to his plans to overhaul Real’s squad. Kante, typically, is happy enough with the Blues. “I am at Chelsea and I still have aims here, what is said elsewhere is not important,” he told RTL. Asked what he would do if Zidane contacted him personally, he replied: “That is not important. I am at Chelsea and I am focused on that.”	cc/2019-30/en_head_0044.json.gz/line3510
__label__wiki	0.574605	0.574605	The Federal Republic of Nepal Contrasts. In two worlds. The democratic federal republic of Nepal is a country between two worlds. Modern, open and ambitious on the one hand; on the other hand it is still shaped by the influence of the caste system that makes it appear limiting and sometimes reactionary. The recent political developments have brought dramatic change: during the past 20 years Nepal has changed from an absolutist monarchy to a democratic federal republic. On 28 May 2008 the republic was established, on 28 August 2011 the current prime minister was elected. It is expected that the new constitution will be adopted in 2012. In this environment, the Nepalese caste system seems to be a limiting constant: For almost 2000 years it has divided the population into acceptable higher caste members and “untouchables”. This is an anachronism that seems to contradict the country’s current political evolution. Thus, Nepal is a nation unlike any other on the Asian continent – it has its own specific characteristics: contrasts in two worlds. These characteristics make it worthwhile for visitors to form their own view of the current situation and future developments. Join us on the next pages to find out more about the country and the people who live here. Arriving in Nepal Travelling around Nepal denk. Contact \| Impressum (legal details) \| data confidentiality statement \| < back to welcome page	cc/2019-30/en_head_0044.json.gz/line3512
__label__wiki	0.767769	0.767769	Back To: Home : Featured Technology : Microbiome Golden touch with zinc fingers by Lori Lesko \| Email the author EDIT CONNECT Nature Methods Cell Systems CAMBRIDGE, Mass.—Armed with new weapons aimed at killing cancer cells and cells infected with a virus, biological engineers at the Massachusetts Institute of Technology (MIT) have developed a modular system of proteins targeted toward detecting a particular DNA sequence in a cell—then triggering a cell death. The technology, described in the Sept. 21 scientific journal Nature Methods, is based on DNA-binding proteins known as zinc fingers. “There is a range of applications for which this could be important,” says James Collins, senior author and Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). “This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection with a report system and/or a respond system.” Shimyn Slomovic, a postdoctoral associate of IMES and lead author on the journal paper about targeting DNA, has said, “The technologies are out there to engineer proteins to bind to virtually any DNA sequence. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection.” Cancer generally works through mutated DNA sequences that are either passed on from previous generations or acquired throughout life and environmental exposure. Therefore, it makes sense that detecting specific DNA mutations that lead to cancer can play a role in combating this disease, Slomovic tells DDNews. “Today, technologies exist that allow researchers and clinicians to read DNA sequences purified from patient cells and discover mutations,” Slomovic explains. “And in parallel, we are getting better at designing proteins to recognize specific sequences, such as those used in our study.” One benefit in using designable proteins for DNA recognition “lies in the ability to interrogate the DNA inside living cells,” she says. “Although there are hurdles to overcome, such protein devices could someday play a direct role in cancer diagnosis and/or treatment and now may be used as research tools that expand our knowledge of the inner workings of cancer.” This platform has the potential to lead to several different avenues, one of which could be the detection of DNA mutations or chromosomal defects that lead to cancer, she notes. “Presently, we are gearing toward the use of this system to aid in identifying and eradicating the HIV provirus, whose DNA can enter a dormant state after it has embedded itself within the human genome,” Slomovic explains. “This latency allows the virus to evade antiviral treatments that are administered to infected individuals—and its eradication may be the final stage in facilitating a cure to the disease.” An additional direction might be to expand the detection repertoire of the current system to include pathogens whose genomes exist as RNA, such as the Ebola virus or SARS. To create their new system, researchers needed to first link zinc fingers’ DNA-binding capability with a consequence: either turning on a fluorescent protein to reveal that the target DNA is present or generating another type of action inside the cell. They linked green fluorescent protein (GFP) production to the zinc fingers’ recognition of a DNA sequence from an adenovirus, so that any cell infected with this virus would glow green. “This approach could be used not only to reveal infected cells, but also to kill them,” Slomovic notes. “To achieve this, the researchers could program the system to produce proteins that alert immune cells to fight the infection, instead of GFP.” “Since this is modular, you can potentially evoke any response that you want,” Slomovic says. “You could program the cell to kill itself, or to secrete proteins that would allow the immune system to identify it as an enemy cell so the immune system would take care of it.” Future versions of the system could be designed to bind to DNA sequences found in cancerous genes and then produce transcription factors that would activate the cells’ own programmed cell death pathways. Adds Collins: “While treating diseases using this system is likely many years away, it could be used much sooner as a research tool. For example, scientists could use it to test whether genetic material has been delivered to cells that scientists are trying to genetically alter. Cells that did not receive the new gene could be induced to undergo cell death, creating a pure population of the desired cells. MIT-engineered viruses could combat human disease, improve food safety CAMBRIDGE, Mass—In the war against harmful bacteria, scientists have turned to a familiar opponent: viruses that infect bacteria. By tweaking the genomes of these viruses, known as bacteriophages, researchers hope to customize them to target any type of pathogenic bacteria. To do this, MIT biological engineers have “devised a new mix-and-match system to genetically engineer viruses that target specific bacteria. This approach could generate new weapons against bacteria for which there are no effective antibiotics,” says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering. Lu is the senior author of a paper describing this work in the Sept. 23 edition of the journal Cell Systems. These modular bacteriophages “could also be used to ‘edit’ microbial communities, such as the population of bacteria living in the human gut, Lu said. “There are trillions of bacterial cells in the human digestive tract, and while many of these are beneficial, some can cause disease.” Some reports have linked Crohn’s disease to the presence of certain strains of E. coli, he added. “We’d like to be able to remove specific members of the bacterial population and see what their function is in the microbiome,” Lu said. “In the longer term you could design a specific phage that kills that bug but doesn’t kill the other ones—but more information is needed to effectively design such therapies.” The Food and Drug Administration (FDA) has approved a handful of bacteriophages for treating food products, but efforts to harness them for medical use have been hampered because isolating useful phages from soil or sewage can be a tedious, time- consuming process,” Lu notes. The journal article explains that after the researchers identified the genes to insert into their phage scaffold, they created a new system for performing the genetic engineering. Existing techniques for editing viral genomes are fairly laborious, so the researchers came up with an efficient approach in which they insert the phage genome into a yeast cell, where it exists as an “artificial chromosome” separate from the yeast cell’s own genome. “Once we had that method, it allowed us very easily to identify the genes that code for the tails and engineer them or swap them in and out from other phages,” Lu said. Code: E111509	cc/2019-30/en_head_0044.json.gz/line3513
__label__wiki	0.899881	0.899881	Tigers doing their best for struggling city Subject: Tigers doing their best for struggling city Mon Jun 22, 2009 11:19 pm Tigers doing their best for struggling city; 'It’s the least we can do' By BOB NIGHTENGALE • USA TODAY • June 22, 2009 It is midday, and the streets in downtown Detroit are nearly desolate. Buildings are vacant. Restaurants are closed. The Borders Books, Music & Cafe on Woodward Avenue, which opened with so much hope nearly six years ago, drawing such celebrities as rapper Grandmaster Flash and actor Hill Harper, is having a huge clearance sale. It, too, is closing its doors in July. “Once you get away from the casino, there’s no people out,” Detroit Tigers centerfielder Curtis Granderson says. ”I had a buddy come to town, saw all of the buildings and houses boarded up, and said, “If I really want to make a killing in this city, I’d invest in plywood.’ ” Granderson tried to manage a weak grin, but not in these times, in a city crippled by the auto industry’s demise, erasing a way of life. With even powerful General Motors filing for bankruptcy protection, Detroit has become the epicenter of the country’s recession. Members of its baseball team can’t help but notice the despair and wonder what they can do to alleviate it. ”It’s so sad to see what’s going on,” Tigers rightfielder Magglio Ordonez says. “They are such hardworking people. They save their money to see us play. ”If nothing else, we have to work hard, play the game right and put a smile on their face. It’s the least we can do.” Not great in ’08 The Tigers were perhaps baseball’s biggest underachievers last year. They had the third-highest payroll, trading for high-priced infielder Miguel Cabrera, former All-Star shortstop Edgar Renteria and former 20-game winner Dontrelle Willis. The Tigers had the city and its fans, with the 2006 World Series appearance still fresh in their minds, thinking it would be a magical year. They instead finished last in the AL Central Division, 74-88. ”We were embarrassed,” Tigers manager Jim Leyland said. This year, they might be baseball’s biggest surprise. The Tigers are in first place in the AL Central with a 38-31 record, four games ahead of the Minnesota Twins. The Tigers might be flawed, benching their most accomplished star (Ordonez) last week, but they are providing hope for a city seeking escape. “What the Tigers are doing means so much to us,” says geologist Paul McDonnell, 43, unemployed since November, attending a game at Comerica Park against the Boston Red Sox. ”People who have troubles come here and forget their problems. “Somewhere along the way, everyone is tied to the auto industry. But just like the economy, you’ve got to look forward to better and brighter days. That’s why people really want to believe in the Tigers.” The Tigers weren’t a big player in the off-season free-agent market, picking up former closer Brandon Lyon ($4.25 million) and light-hitting shortstop Adam Everett ($1 million), who replaced departed Renteria. They traded for catcher Gerald Laird from the Texas Rangers and pitcher Edwin Jackson, a spare starter with the Tampa Bay Rays. The moves were so uninspiring that, coupled with the economy, the season ticket base plummeted from 28,500 to 15,000. The Tigers are averaging 28,000 fans a game -- fourth in the AL and 12th in the major leagues -- but their 10,000 drop-off is the second largest in baseball. GM bailed out on its marquee advertising spot above the batter’s eye at the centerfield fountains. And many of the corporations that had suites gave them up or share them. Tigers owner Mike Ilitch, who had a corporation willing to pay $1.5 million for GM’s spot, decided to let GM advertise free, while also flanking the area with logos from Chrysler and Ford. Underneath is a sign that reads, ”The Detroit Tigers support our automakers.” “No part of the country has been hit like us,” says Ron Colangelo, Tigers vice president. ”But there’s a real emotional bond here. You can feel it. People are very resilient.” At the start of the season, Leyland told his team that everyone would be running out ground balls and pop-ups this year. “It won’t be tolerated by this community if they don’t give that,” says Dave Dombrowski, Tigers president and general manager. ”The economy has taken a toll on everyone, but particularly here. You can’t control the outcome of games, but the one thing you can control is effort.” Jackson is staff surprise The Tigers, with only two players who live full time in Michigan, realize they can’t be saviors. They can’t reduce the city’s 15% unemployment rate or stop the free fall in housing prices, dipping to an average of $18,500. Capturing their first World Series title since 1984 would be a storybook finish, but this is reality, not Hollywood. “I don’t think anybody is thinking, 'Hey, we’ve got to win for the city,’ ” Granderson says. “But we definitely know we’ve got to make that effort. ... especially when people are spending their last bit of money to watch us. And I think we’re showing that.” The Tigers, who are 10th in the league in offense but second in pitching, are conscious of their role. Few complaints are voiced publicly. Even when Ordonez, 35, and his $18 million salary was ”indefinitely benched” last week, he remained quiet, saying simply that he is confident he can work through his struggles. It was his agent, Scott Boras, and Leyland who exchanged barbs. Ordonez, a six-time All-Star, is hitting .273 but has only two homers and 11 extra-base hits. “When you get older and struggle,” Ordonez says, ”people say crazy stuff. I’ll be fine. I think our whole team will start hitting. “But as long as you play good defense and have good pitching, you have a chance to win. Look at the last two years. We hit like crazy. Where did it get us? Nowhere. It’s different this year.” The Tigers' starting rotation, which had two pitchers win at least 10 games in 2008, again has been erratic. The top three starters -- ace Justin Verlander, rookie Rick Porcello and Jackson -- are 22-11 with a 3.05 ERA. But the back end is 3-6 with a 6.20 ERA. Verlander, who went 11-17 with a 4.84 ERA last season, is 8-3 with a 3.31 ERA, leading the league with 118 strikeouts. Porcello, 20, who had not pitched above Class A Lakeland until this year, has an 8-4 record and 3.54 ERA. And then there is Jackson, cast off when the Rays no longer thought he fit in their plans. He is 6-4 with a 2.39 ERA, second-lowest among AL starters. ”He’s the biggest surprise on our team,” Ordonez says. “Everybody knew he was good, but he’s been unbelievable.” Jackson has been relying on a 94- to 98-m.p.h. fastball that he’s been able to locate for strikes. He recorded strikes in 64 of his 99 pitches in his last start, against the St. Louis Cardinals. He has yielded three or fewer earned runs in all but two games this season, including eight consecutive starts. He is becoming an overnight hero in Detroit. ”It’s been great here,” Jackson says. “It’s such a great sports city. I still can’t believe when people come up to me and say, 'Edwin Jackson?’ I just sit back and laugh. “Now if I can be pitching in October in the playoffs, that would be great. Detroit would be going off, and after everything it’s gone though, it’d be nice to cheer them up and give them some excitement.” Says Granderson, who leads the team with 17 homers, ”This city has a never-say-die attitude, and it’s the same with us. We can be down but not out. I think together we can make something special happen.” Location : Trashy Park Michigan Favorite Current Tiger(s) : Dontrelle Willis, Brandon Inge, Maggs, Verlander, Granderson, Pudge and Todd Jones Subject: Re: Tigers doing their best for struggling city Tue Jun 23, 2009 4:50 pm Maggs needs to play » LEICESTER CITY PROGRAMMES » WORCESTER CITY v HARROGATE TOWN » Man City 3 Town 2 » Sunderland v Man City	cc/2019-30/en_head_0044.json.gz/line3514
__label__cc	0.714739	0.285261	1234..2829 Andrew Jackson. Andrew Jackson. Seventh President of the United States. Armory of Colt's Patent Fire Arms Manufacturing Company. Assassination of Colonel Elmer E. Ellsworth. Assassination of President Lincoln, Ford's Theater, Washington, April 14. 1865. Atlanta, Georgia. As it Appeared on the Entrance of the Union Army Under Genl. Sherman, Sept. 2d. 1864. Attack on the City of Mexico. Attack Upon Fort Sumter April 12th. & 13th. 1861, by the Southern Rebels. Augusta. Auld Lang Syne. Plate 1. Awful Conflagration of the Steam Boat Lexington. Ayrshire Cow Dolly 3rd. Ayrshire Cow Flora 2nd. Bacon Academy, Colchester, Conn. Basket of Fruit. Battle at Bunkers Hill. (Near Boston) Battle at Bunker's Hill. (Near Boston) Battle at Missionary Ridge, Ga. Battle of Antietam, Md. Sept. 17. 1862. Battle of Baton Rouge, La. Aug. 6th. 1862. Battle of Buena Vista. Battle of Bull's Run, Va., July 21. 1861. Battle of Bull's Run, Va., July 21st. 1861. Battle of Cerro Gordo. April 18th, 1847. Battle of Champion Hills, Miss, May 16th. 1863. Battle of Chancellorsville, Va. May, 3rd. 1863. Battle of Contreras. Near Mexico - August 20th. 1847. Battle of Eylau. Battle of Fair Oaks, Va. June 1st. 1862. Battle of Lexington, Missouri, from the 16th. to the 21st. of Sept. 1861. Battle of Lodi. Battle of Mill Spring, Ky. Jan. 19th. 1862.	cc/2019-30/en_head_0044.json.gz/line3516
__label__cc	0.70028	0.29972	China looks to further progress Last Updated: 2018-11-07 13:45 \| China Daily World Internet Conference to be a launchpad for online shared future As the Fifth World Internet Conference kicks off, the internet industry enters "Wuzhen time" again. An ancient town in Zhejiang province, Wuzhen has witnessed tremendous changes and become the epicenter of China's internet-driven industries and online innovation, since it was made the permanent home of the World Internet Conference in 2014. Its rapid growth in recent years also demonstrates how the benefits of development can be shared, a concept embodied by the global internet industry. Over the past five years, the Wuzhen summit has been an international beacon of connectivity and communication for the world, and a platform for sharing and joint governance in China. The influence of the summit has continued to expand, enabling more countries and people to ride the express train of the "information age" and share the fruits of an even-better internet. From connectivity, sharing and joint governance, to developing a digital economy for greater openness, the focus of the conference may advance and change with the hot topics of the day, but China's determination and sincerity in the building of a community with a shared future in cyberspace has remained consistent. The "Four Principles" and "Five points" proposed by President Xi Jinping, especially his concepts for internet governance, such as cyber sovereignty, has resonated throughout the industry. From the first to the fourth conference, China's proposition has won widespread praise, showing that the nation has grown from one of the beneficiaries of global internet development, to become a contributor and leader, as well as highlighting China's willingness to face up to the responsibility that comes with that role. The previous conferences have also demonstrated deep insights into global internet trends and their positive outcomes, such as the Wuzhen Initiative proposed by 2015's conference, the 2016 Wuzhen Report on World Internet Development, and the Wuzhen Outlook released during last year's conference. President Xi has said it is a goal for all Chinese people to enjoy the fruits of internet development, and for it to better benefit people of all countries. How do we realize these shared benefits? China's solutions serve as the answer, and its ideas and practices on internet development and governance are spreading to the whole world from Wuzhen. As an increasingly important driving force of the global economy, the digital sector is playing a crucial role in accelerating growth. The World Internet Conference will not only provide an exchange platform for the development of global digital economy, but also push its development into a new era. In December 2017, the relevant departments from China, Laos, Thailand, Turkey, United Arab Emirates, Saudi Arabia, Serbia, among others, jointly launched the Initiative for International Cooperation of the "Belt and Road" Digital Economy. The initiative welcomes countries around the world to benefit from the wisdom, experience and solutions garnered through China's own digital economic development. In recent years, the development of China's internet industry has been remarkable, and has constantly found success in foreign markets, benefiting the world at large. China's propositions and solutions are also contributing unique values to the development of world internet governance. The innovative development of China's internet economy also provides a broad market space for enterprises and entrepreneurs in various countries. By May 2017, Chinese internet enterprises had participated in the construction of information infrastructure in more than 170 countries, completed 34 cross-border land cables, and several international sea cables in cooperation with 12 countries involved in the Belt and Road Initiative. Meanwhile, with their advanced digital technology and innovative business models, Chinese enterprises have cooperated with many countries in various fields, such as mobile payment, smart city initiatives and e-commerce, to share achievements in digital technology with the world. For instance, today, Chinese bike-sharing services are promoted and available in 21 countries and regions around the world. In recent years, China has actively carried out bilateral and multilateral international exchanges and cooperation, contributing its own strength to the governance of cyberspace, participating in bilateral and multilateral dialogues led by international organizations such as the United Nations. China has emphasized informatization in the construction of its Belt and Road Initiative, in hope of improving international connectivity through an online Silk Road. Starting from Wuzhen, the country is already on the way to build a peaceful, secure, open and cooperative cyberspace, as well as establish a multilateral, democratic and transparent global system. Source: www.cac.gov.cn, the official website of the Office of the Central Cyberspace Affairs Commission. Light of Internet Exposition reflects high-tech advances [ 2018-11-07 ] Anti-fraud startup reaps WIC fruits [ 2018-11-07 ] IT-enabled businesses will instill new energy in economy [ 2018-11-07 ] Xi's vision sets tone for event [ 2018-11-07 ] A blue welcome: Volunteers ready for WIC [ 2018-11-07 ] Source:China Daily \| 2018-11-07 13:45	cc/2019-30/en_head_0044.json.gz/line3517
__label__cc	0.638264	0.361736	Items where Division is "Faculty of Health and Social Sciences > School of Clinical and Applied Sciences" and Year is 2010 Jump to: A \| B \| C \| M \| N \| S \| T \| W \| Y Alabas, OA and Tashani, OA and Tabasam, G and Johnson, MI (2010) Gender role expectation of pain predicts response to experimentally-induced pain in healthy Libyan participants. In: 13th World Congress of the International Study of Pain Congress, Montreal, Canada. Baker, G and Maynard, M and Rawlins, E and Harding, S (2010) Developing obesity prevention interventions among minority ethnic children in schools and places of worship: The DEAL study. Obesity Reviews, 11 (Suppl). 456 - 456. ISSN 1467-789X DOI: https://doi.org/10.1111/j.1467-789X.2010.00763_7.x Coates, C and Taylor, J (2010) Promoting the concept of competency maps and interprofessional assessments linked to e-portfolios to enhance the student learning experience in preparation for work based learning, employability and life long learning. In: Eden Conference, 9th - 12th June 2010, Valencia, Spain. Maynard, MJ and Harding, S (2010) Ethnic differences in psychological well-being in adolescence in the context of time spent in family activities. Social psychiatry and psychiatric epidemiology, 45 (1). 115 - 123. ISSN 0933-7954 DOI: https://doi.org/10.1007/s00127-009-0047-z Maynard, MJ and Harding, S (2010) Perceived parenting and psychological well-being in UK ethnic minority adolescents. Child: care, health and development, 36 (5). 630 - 638. ISSN 0305-1862 DOI: https://doi.org/10.1111/j.1365-2214.2010.01115.x Newton, LAA and Cowham, E and Sharp, D and Leslie, R and Davis, J (2010) Plumbagin: A natural product for smart materials? New Journal of Chemistry, 34 (3). 395 - 397. ISSN 1144-0546 DOI: https://doi.org/10.1039/b9nj00534j Sahota, P and Wordley, J and Woodward, J (2010) Literature Review - Health behaviour change models and approaches for families and young people to support HEAT 3: Child Healthy Weight Programmes. Project Report. NHS Health Scotland. Schrettl, M and Carberry, S and Kavanagh, K and Haas, H and Jones, GW and O'Brien, J and Nolan, A and Stephens, J and Fenelon, O and Doyle, S (2010) Self-protection against gliotoxin--a component of the gliotoxin biosynthetic cluster, GliT, completely protects Aspergillus fumigatus against exogenous gliotoxin. PLoS pathogens, 6 (6). e1000952 - ?. ISSN 1553-7366 DOI: https://doi.org/10.1371/journal.ppat.1000952 Tapp, RJ and O'Neil, A and Shaw, JE and Zimmet, PZ and Oldenburg, BF and AusDiab Study Group (2010) Is there a link between components of health-related functioning and incident impaired glucose metabolism and type 2 diabetes? The Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care, 33 (4). pp. 757-762. ISSN 1935-5548 DOI: https://doi.org/10.2337/dc09-1107 Tashani, OA and Johnson, MI (2010) Avicenna's concept of pain. The Libyan journal of medicine, 5. 164 - 165. ISSN 1993-2820 DOI: https://doi.org/10.3402/ljm.v5i0.5253 Waby, JS and Chirakkal, H and Yu, C and Griffiths, GJ and Benson, RS and Bingle, CD and Corfe, BM (2010) Sp1 acetylation is associated with loss of DNA binding at promoters associated with cell cycle arrest and cell death in a colon cell line. Molecular cancer, 9. 275 - ?. DOI: https://doi.org/10.1186/1476-4598-9-275 Whitrow, MJ and Harding, S and Maynard, MJ (2010) The influence of parental smoking and family type on saliva cotinine in UK ethnic minority children: a cross sectional study. BMC public health, 10. 262 - ?. DOI: https://doi.org/10.1186/1471-2458-10-262 Yu, DC and Waby, JS and Chirakkal, H and Staton, CA and Corfe, BM (2010) Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Molecular cancer, 9. 276 - ?. DOI: https://doi.org/10.1186/1476-4598-9-276	cc/2019-30/en_head_0044.json.gz/line3519
__label__wiki	0.974134	0.974134	No Rutgers strike: Faculty union reaches last-minute deal with university By Kelly Heyboer Rutgers University averted what would have been the first strike by professors in the school’s nearly 253 -year history by reaching a last-minute deal late Tuesday with the faculty union in a series of marathon negotiating sessions. The state university and the Rutgers AAUP-AFT, which represents 4,800 full-time faculty and graduate workers, announced the deal for a new contract. The agreement still needs to be approved by the full union. “We made history today,” Rutgers AAUP-AFT president Deepa Kumar said in a statement. “For the first time in the union’s nearly 50-year history, we won equal pay for equal work for female faculty, faculty of color and for faculty in the Newark and Camden campuses. We won significant pay raises for our lowest paid members, our graduate employees who will see their pay increase from $25,969 to $30,162 over the course of the contract.” A press conference is planned for 10 a.m. Wednesday on the New Brunswick campus, where more details about the deal are expected to be announced. “I can confirm there is a settlement and we will be issuing a joint statement tomorrow,” said Dory Devlin, a Rutgers spokeswoman. Kumar said university and union officials came to an agreement on several other issues, including calls for more diversity in hiring at Rutgers and protections for professors who make controversial statements on Twitter and Facebook. “In other historic firsts, the union won $20 million for diversity hiring and a guarantee of a workplace free of harassment and stalking, enforced with binding arbitration,” Kumar added. “Academic freedom now applies to social media.” David Hughes, the union’s vice president, said the new contract includes more protection for graduate students and non-tenure-track faculty, who will be eligible for contracts up to seven years. “Furthermore, in this climate of insecurity for immigrants, the union worked hard to revise the university’s ‘no-green card’ policy, Rutgers may now sponsor (non-tenure-track) faculty for permanent residency,” said Hughes, who headed the union’s bargaining team. The settlement came after several days of lengthy negotiating sessions that included mediators brought in to help the two sides agree on raises and other issues that had left them deadlocked for months, union officials said. About 88 percent of Rutgers faculty union members voted last month to authorize union leaders to call a historic strike, if necessary. The union had already printed “Strike” signs and begun training faculty on how to walk picket lines. Professors and other faculty would have cancelled classes and stopped all research on the New Brunswick-Piscataway, Newark and Camden campuses if a strike was called. They also would have asked part-time adjunct professors, who are not in their bargaining unit, to honor picket lines and not teach classes. It is unclear how a strike would have affected finals, graduation and the end of the spring semester for Rutgers’ nearly 70,900 undergraduate and graduate students. The university did not announce any contingency plans. Rutgers’ top professors are among the best paid public university faculty in the nation. The average salary for a full-time professor at Rutgers-New Brunswick was $145,458 in 2016, according to an analysis by the Chronicle of Higher Education. But full professors are a small part of Rutgers faculty, union officials said. Assistant and associate professors can earn far less and Rutgers’ Newark and Camden campuses also average less than their counterparts in New Brunswick, union officials said. About 1,000 of the union’s members have full-time salaries starting at $60,000 a year, according to the union’s data. Though the faculty union deal is settled, Rutgers still need to reach contracts with several other unions, including its 3,000 part-time adjunct lecturers who teach many of the university’s classes. The faculty union called on students, professors and staff to join them for “solidarity” rallies Wednesday at: 11:20am at the Walt Whitman statue on the Camden campus; 2:30 p.m. on the steps of the student center in Newark; and 4 p.m. on the new Paul Robeson Plaza on College Avenue in New Brunswick. This story originally appeared on NJ.com here.	cc/2019-30/en_head_0044.json.gz/line3521
__label__cc	0.544258	0.455742	The FCI General Committee was truly sorry to hear of the loss of Mr Hans Lehtinen. He was a great and appreciated person and a most valuable judge. He was a real asset to Finnish cynology and to the world of pure-bred dogs! The well-known Finnish all round judge and Honorary Member of the Finnish Kennel Club, Mr Hans Lehtinen passed away on Tuesday the 1st of March due to a serious illness. He was a very respected judge all over the world and was known for his phenomenal eye for dogs. He judged around the globe and at many of the most important shows like the FCI World Dog Show and FCI Section Shows as well as Crufts, the Royal Shows in Australia and shows like Santa Barbara in USA. He judged the Best In Show at the FCI World Dog Show 2014 in Helsinki, Finland. Mr Lehtinen was a mentor for many new judges as well as for numerous judges learning new breeds. He was a member of different committees of the Finnish Kennel Club and had positions in several breed clubs and associations. His contribution to the dog sport in Finland and abroad has been immense and he will be greatly missed by many dog enthusiasts around the world. Rafael de Santiago FCI President	cc/2019-30/en_head_0044.json.gz/line3522
__label__wiki	0.960713	0.960713	Electronic Hot Sale > Blog > Computers > John Walker Lindh, American who became Taliban fighter, released from prison after 17 years – USA TODAY John Walker Lindh, American who became Taliban fighter, released from prison after 17 years – USA TODAY The “American Taliban” who volunteered at an al-Qaeda training camp was released from prison after 17 years. These are 5 things to know about John Walker Lindh. A California man dubbed the “American Taliban” following his captureÂ on a battlefield in Afghanistan in 2001 was released from prison Thursday after serving 17 years, authorities confirmed,Â amid allegations ofÂ his continued adherence to extremist views. The Federal Bureau of Prisons confirmed that John Walker Lindh, 38,Â who was serving his sentence at the federal prison in Terre Haute, Indiana, was no longer in its custody.Â Lindh, who was convicted of providing support to the Taliban,Â was freedÂ three years early for good behavior, according to CNN, which first reported theÂ release. Lindh, the son of a Justice Department lawyer who grew up in a San Francisco suburb,Â was captured in a battle with Northern Alliance fighters in late 2001. Video footage showedÂ Lindh â weak, dirty and almost incoherent from apparent battlefield injuriesÂ â laying on a cot in a detention center. American John Walker Lindh is seen in this undated file photo obtained in Januaary 2002, from a religious school in Bannu, Pakistan where he studied for five months. Lindh, the young Californian who became known as the American Taliban after he was captured by U.S. forces in the invasion of Afghanistan in late 2001, was freed in May 2019 after nearly two decades in prison. (Photo: AP) Start the day smarter: Get USA TODAY’s Daily Briefing in your inbox A CNN camera filmed Lindh, in halting English, tellingÂ American forces how he had wound up at a detention camp in northern Afghanistan and survived a Taliban uprising there that killed hundreds of prisoners and CIA officer Mike Spann. Secretary of State Mike Pompeo slammed the release, calling it “unexplainable and unconscionable.â Pompeo said in an interview with FoxÂ News that Lindh “still is threatening the United states of America, still committed to the very jihad that he engaged in that killed a great American and a great CIA officer. Thereâs something deeply troubling and wrong about it.” Lindh’sÂ release was also opposed by Spann’sÂ family. The CIA officer’s father, Johnny Spann, called Lindh a traitor on Twitter, charging that he “knew they were going to attack America, stayed with them, training in Al QuedaÂ camps. He appealed to President Donald Trump to block the release.Â Lindh was not accused of participating in the killing, but was present during the attack, according to authorities. Lindh admitted to participating in the revolt near Mazar-e Sharif, Afghanistan, but prosecutors did not say that he had a role in Spann’s death. HisÂ freedom comes with court-imposed restrictions, including software on his internet devices. He is required toÂ only use EnglishÂ online andÂ toÂ surrender his passport. He alsoÂ is banned from viewing or possessing extremist material, and is required toÂ undergo mental health counseling. Lindh, raised a Catholic,Â converted to Islam as a teenager after seeing the film “Malcolm X” andÂ went overseas to study Arabic and the Koran. In November 2000 he traveledÂ to Pakistan and from there made his way to Afghanistan where he wasÂ a volunteer at an al-Qaeda training camp. He was with the Taliban at the time of the 9/11 attacks and was captured in the U.S.-backed retaliatory raids on Afghanistan. In his trial in 2002, Lindh pleaded guilty to serving in the Taliban army and carrying weapons but denied taking up arms against the U.S. “I did not go to fight against America, and I never did,” Lindh told the court. “I have never supported terrorism in any form, and I never will. . . . I made a mistake by joining the Taliban. Had I realized then what I know now, I would never have joined them.” In the run-up to Lindh’s release, Foreign PolicyÂ reported that two government documents it obtained expressedÂ concerns about Lindh’sÂ extremist views. One document, from the NationalÂ Counterterrorism Center, found that as ofÂ 2016 Lindh “continued to advocate for global jihad and to write and translate violent extremists texts,” the magazine reported. According to Foreign Policy, the document, which cites various Federal Bureau of Prisons intelligence summaries, claims that in March of last year, Lindh âtold a television news producer that he would continue to spread violent extremist Islam upon his release.â The TV producer is not identified, no specific statements are quoted, and there is no public record that Lindh has participated in media interviews, according to the magazine. The Bureau of Prisons said it cannot comment specifically on Lindh’s case, but noted that it has policies and proceduresÂ for monitoring communications of inmates with known or suspected ties to domestic and foreign terrorism and “shares information with law enforcement as appropriate.” The BOP, citing studies by its staff, says it “has found that many inmates have turned away from radicalized ideology in prison based on self-study or due to participation in programming or sentence length.” “While we are aware of a small number of this population who have returned to BOP custody, none have returned to BOP custody for terrorism-related charges,” the bureau said. A U.S. Army carry team moves a transfer case containing the remains of Capt. Andrew P. Ross on Nov. 30, 2018, at Dover Air Force Base, Del. According to the Department of Defense, Ross, 29, of Lexington, Va., was killed Nov. 27, 2018, by a roadside bomb in Andar, Ghazni Province, Afghanistan. PATRICK SEMANSKY, AP Tucker Magnuson, 2, of Lacon, says goodbye to his uncle, Sgt. Kenny Steele, right, who is headed out on his fourth tour to Afghanistan, as family and loved ones gather with members of Bravo Company, 2nd Battalion, 238th Aviation Regiment during a deployment ceremony at the guard’s aviation facility near the Gen. Wayne A. Downing Peoria International Airport on Aug. 24, 2017, in Ill. The unit will fly out for training on their way to deployment in support of Operation Freedom’s Sentinel. Fred Zwicky, Journal Star via AP An Army carry team moves a transfer case containing the remains of Staff Sgt. Aaron R. Butler at Dover Air Force Base, Del. on Aug. 18, 2017. According to the Department of Defense, Butler, of Monticello, Utah, died Aug. 16, in Nangarhar province, Afghanistan, of injuries sustained from an improvised explosive device while conducting combat operations. Steve Ruark, AP In this Aug. 5, 2015 file photo, an Afghan National Army soldier, left, smokes as a U.S. Army soldier from Charlie Company, 2-14 Infantry Regiment, 2nd Brigade, 10th Mountain Division sits next to him in Camp Khogyani in Nangarhar province, east of Kabul, Afghanistan. An uptick in attacks by Afghan National army soldiers against foreign troops would seem a worrisome trend ahead of the deployment of another 4,000 U.S. troops to Afghanistan in the latest attempt by Washington to turn around the protracted war against insurgents. Massoud Hossaini, AP A US army flight crew chief Sgt Cory Rodgers, left, from Company C, 1st Battalion, 52nd Aviation Regiment, MEDEVAC team wipes the face of a wounded US Army soldier on their Blackhawk helicopter over Kandahar province in southern Afghanistan on March 28, 2011. Around 140,000 foreign troops are deployed in Afghanistan within the UN-mandated, NATO-led, International Security Assistance Force (ISAF) and the US-led coalition Operation Enduring Freedom, which overthrew the Taliban in late 2001. Peter Parks, AFP/Getty Images In this Nov. 3, 2010 file photo, an Afghan boy watches Cpt. Chris Esrey of Havelock, North Carolina, with India, 3rd Battalion 5th Marines, First Marine Division, company, scan the area during a patrol in Sangin, south of Kabul, Afghanistan. Reversing his past calls for a speedy exit, President Donald Trump recommitted the United States to the 16-year-old war in Afghanistan, declaring on Aug. 21, 2017 U.S. troops must Âfight to win.Â He pointedly declined to disclose how many more troops will be dispatched to wage America’s longest war. Dusan Vranic, AP In this March 18, 2010 file photo, U.S. Marine Lance Cpl. Mathew Gorzkiewicz, of North Liberty, Indiana, with the First Battalion, Sixth Marine Regiment, Alpha company, tries out an Afghan boy’s sling during a patrol in Marjah, Afghanistan. Reversing his past calls for a speedy exit, President Donald Trump recommitted the United States to the 16-year-old war in Afghanistan, declaring on Aug. 21, 2017 U.S. troops must “fight to win”. He pointedly declined to disclose how many more troops will be dispatched to wage America’s longest war. Dusan Vranic, AP	cc/2019-30/en_head_0044.json.gz/line3524
__label__cc	0.674737	0.325263	Concert/Culture/Art very LONG very SLOW: Piano Concert by Ian Power This event occurred in the past. Composer and multi-instrumentalist Ian Power will perform a concert of works for piano by himself, Carolyn Chen, and Erik Satie, as well as two Fluxus pieces by Mieko Shiomi and Alison Knowles on Saturday, December 6 at 1 p.m. The concert is free and open to the public ($5-10 suggested donation) and will be held at An die Musik Live! in Mount Vernon. Because the music on this concert is very long, slow, quiet, and meditative, audience members are encouraged to move around the space, take breaks, and sit, lay, or stand. Power will perform Boundary Music by Mieko Shiomi (b. 1938), My Young Life Has an End by Carolyn Chen (b. 1983), and French impressionist Erik Satie's (1866-1925) lesser known mystical work Les Sonneries de la Rose + Croix. Power will also play two of his own compositions, Construction Song (after Dick Higgins), and Ave Maria: Variations on a Theme by Giacinto Scelsi. Alison Knowles' (b. 1933) Chair Music for George Brecht will be installed throughout. Ian Power is an avant-garde composer and multi-instrumentalist, a Ph.D. candidate at Harvard University under the advisement of Chaya Czernowin, currently living in Baltimore. Born in Rochester, N.Y. in 1984, he studied at UC San Diego and Ithaca College, attending classes and workshops at the Brevard Music Center, the Darmstadt New Music Summer Courses, and the Akademie Schloss Solitude in Stuttgart. He has also studied with John Luther Adams, Steven Takasugi, Amnon Wolman, Antoine Beuger, and Robert Morris. The New York Times has praised his work's “resolute ooze and elemental graininess”; accordionist and composer Pauline Oliveros once called him “a tough act to follow.” Music style Acoustic From the producer Sign In or Register to write a review of the very LONG very SLOW: Piano Concert by Ian Power From the producer: In my own words, finally! Want to speak directly to your fans and followers from this page? Enhance your listing and you can share news, notes and press releases about your event right here. Have a theme night coming up? Want to post a different write-up of your event? Spread the news in your own words. Promotions: Last-minute deal on tickets! Share information about limited-time ticket deals, offerings and other promotions with Carroll County Times users, right here, by enhancing your event listing Click here to get more information and sign up. very LONG very SLOW: Piano Concert by Ian Power Calendar	cc/2019-30/en_head_0044.json.gz/line3527

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