text stringlengths 110 576k | id stringlengths 47 47 | dump stringclasses 1
value | url stringlengths 14 2.54k | date stringlengths 20 20 | file_path stringclasses 376
values | language stringclasses 1
value | language_score float64 0.65 1 | token_count int64 55 141k |
|---|---|---|---|---|---|---|---|---|
Tour duration: approximately 45 minutes
Gain deeper insight into the Australian Museum's vast cultural and scientific collection with our free 45 minute introductory tour of our permanent galleries lead by our Volunteer guides.
These tours run on weekdays, Monday to Friday and are subject to availability as they are led by Australian Museum Volunteers. On arrival please ask Admissions Desk staff for daily tour times.
The Australian Museum is COVID Safe
To help keep our staff, visitors and community safe, the AM has COVID-19 protocols in place, including physical distancing, increased cleaning and hygiene practices. Facemasks are encouraged.
View our full COVID-19 safety information here. | <urn:uuid:8f25f08d-d028-4e87-8a74-58ea01bf8098> | CC-MAIN-2023-40 | https://australian.museum/event/highlight-tours/ | 2023-09-28T18:59:23Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.940487 | 136 |
My son has a diagnosis of Level 1 autism from Utah – I have heard that he must be retested by a certified autism center in Michigan to receive coverage for things like ABA therapy. Can you tell me if this is true, is there any way around this (I hate putting him through all of this ongoing extensive testing) and if it is true how to get on a waiting list. Thanks!
Re-testing at an approved autism evaluation center (AAEC) may or may not be needed. Some insurance providers like Blue Cross Blue Shield of MI and Blue Care Network require an AAEC evaluation to make or confirm a diagnosis of autism in order for applied behavior analysis (ABA therapy) to be covered, but other insurance providers do not have this same requirement. If your insurance plan offers an autism benefit, call the mental health service number on the back of your card and ask what is needed to establish eligibility for autism services.
If your child was evaluated for autism within the past year and an AAEC evaluation is required, the AAEC team may choose to review previous test records to determine if any additional assessment is necessary. In some cases, a full re-evaluation may not be needed, but if your child’s evaluation is over a year old and was not comprehensive, additional testing will probably be needed.
A comprehensive autism evaluation should include assessments of language and communication, adaptive behavior, social abilities, and behavioral, cognitive and emotional functioning. A thorough medical history and examination should also be completed along with parent or caregiver interviews (Autism Diagnostic Interview-Revised/ADI-R) and observation of direct play Autism Diagnostic Observation Schedule/ADOS). If an autism diagnosis is made or confirmed, the level of support needed should also be specified: Level 3- requiring very substantial support, Level 2-requiring substantial support or Level 1-requiring minimal support.
Contact any AAEC to schedule an appointment. A list of AAECs in Michigan can be found by clicking on the following link. List of Approved Autism Evaluation Centers in Michigan
If you need additional help understanding your autism benefits, identifying whether or not your child needs a re-evaluation, or determining where to go for testing, let us know! Call the Autism Alliance of Michigan (AAoM) at 877-463-2266 or click on MiNavigator Program to request a free AAoM Navigator who will work with you to answer your questions and get you where you need to be! | <urn:uuid:e064a351-d654-44d5-9bf8-896bb70fb000> | CC-MAIN-2023-40 | https://autismallianceofmichigan.org/does-my-son-have-to-be-retested-in-michigan/ | 2023-09-28T16:42:02Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.918764 | 517 |
Shop our vast selection of automotive, marine, and RV washes, cleaners, and shampoos. We have meticulously tested each and every wash on this page to make sure it meets our stringent quality standards.
Not all washes are created equal! Inexpensive car washes that are sold over the counter can often create water spots and strip the wax off your vehicle. The washes found on this page are pH-balanced, contain water softeners, and most importantly they will not strip your wax protection. | <urn:uuid:c913bb20-b24a-4111-afb4-06526eacd407> | CC-MAIN-2023-40 | https://autoforge.net/collections/washes-cleaners | 2023-09-28T18:53:52Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.950552 | 103 |
Service 0 - 24 h
AUTO TAXI ERSTIĆ
Kombi Renault Trafic
Passat Variant, Gray
Passat Variant, White
Welcome to our taxi service, where we have been providing reliable transportation solutions for over 20 years.
Our team of experienced drivers are available 24/7 to ensure that you reach your destination safely and on time.
We have a fleet of vehicles including a spacious van and a comfortable car to suit your transportation needs. Our van is perfect for group travel, family outings, and airport transfers, while our car is ideal for individual passengers, business trips, and city tours.
At our taxi service, we pride ourselves on our commitment to customer satisfaction. Our drivers are courteous, knowledgeable, and always willing to go the extra mile to ensure that you have a comfortable and stress-free ride. Whether you’re heading to a business meeting, a special event, or just need a ride around town, we’ve got you covered. | <urn:uuid:ac2ae4d8-4d49-42e4-938a-b0f177bda8ac> | CC-MAIN-2023-40 | https://autotaxi-erstic.hr/ | 2023-09-28T18:41:00Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.904207 | 219 |
Prepping Your Apartment For Short-Term Trips
Welcome to the ultimate list for preparing your apartment before a short trip. After all, your trip should be as enjoyable and as fun as possible, but you’ll only be able to relax if you know that your home is fine while you are away.
Here are some tips for prepping your apartment for short-term trips.
Check All Windows And Doors
Sometimes the most obvious tasks to make the list are the ones that we overlook the quickest. You won’t believe how many people leave a front door unlocked, don’t close windows, or even forget to close the garage to their apartment. When you live in a community with a lot of other people – some of which you may not be as reputable as you want – then you need to ensure that you do the simplest of tasks before going on vacation. In this case, that means closing all the windows and doors in your apartment.
Get Rid Of Any Loose Spare Keys That Might Be Hidden
Having a spare key might work for when you are home every day and you can check on things regularly. However, that spare key might be more of a problem than anything when you go on vacation. One problem is that you never know who else knows about that key. In addition, when you consider how easy it is to use a key to open a door without making it look suspicious, it’s very important that you avoid letting this happen.
Tech Up Your Home
Having technology in your apartment will do you wonders when going out on vacation for a short period of time. One example of technology that you can get includes climate controlled sensors that you can alter from your smartphone, computer or tablet. These systems are perfect for controlling the temperature of your apartment while away, and some even have features that control other parts of your home like lighting. Investing in some new technology for your apartment might be just what you need for peace of mind while on vacation.
Another example of some technology that you can outfit for your home includes cameras. Like the aforementioned climate control systems, the cameras can also be accessed through a smartphone. This means that you can keep an eye on your home, even while you are out on the road.
…Or Just Make It Look That Way
Even if your home isn’t well equipped with state of the art technology to protect it, you can at least make it look as such. Pick up some fake cameras and throw them on the balcony, or simply put a sign in the window that says you have security, and you’ll be surprised with how well this can detract unwanted visitors while you are away.
Ask For Help
Finally, consider asking someone you trust for help. This might be a family member or friend, and they can help with checking on things to make sure everything is alright. In addition, they can also check the mail or pick up the newspaper, which will help to make it look like someone is home.
Before you hit the road, even if it’s just for a quick trip, be sure to consider the tips her. They’ll help you relax and enjoy your vacation. | <urn:uuid:f38e7632-bec5-4f7b-b847-189e184ff9d9> | CC-MAIN-2023-40 | https://autumnparkapts.com/blog/prepping-your-apartment-for-short-term-trips/ | 2023-09-28T17:47:28Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.963534 | 651 |
It is a well-felt recent phenomenal fact that global food prices have dramatically increased and attracted attention from practitioners and researchers. In line with this attraction, this study uncovers the impact of global factors on predicting food prices in an empirical comparison by using machine learning algorithms and time series econometric models. Covering eight global explanatory variables and monthly data from January 1991 to May 2021, the results show that machine learning algorithms reveal a better performance than time series econometric models while Multi-layer Perceptron is defined as the best machine learning algorithm among alternatives. Furthermore, the one-month lagged global food prices are found to be the most significant factor on the global food prices followed by raw material prices, fertilizer prices, and oil prices, respectively. Thus, the results highlight the effects of fluctuations in the global variables on global food prices. Additionally, policy implications are discussed. | <urn:uuid:b54a0ac3-5663-4657-a170-0f0ef7e776b4> | CC-MAIN-2023-40 | https://avesis.anadolu.edu.tr/yayin/cbd9a471-79b3-4dfe-91fb-0f5e335640b6/estimation-of-impacts-of-global-factors-on-world-food-prices-a-comparison-of-machine-learning-algorithms-and-time-series-econometric-models | 2023-09-28T17:39:41Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.923403 | 177 |
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED, vol.46, no.5, pp.849-853, 2015 (SCI-Expanded)
Article / Article
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
Science Citation Index Expanded (SCI-EXPANDED), Scopus
Chest trauma, CT, Emergency radiology, Thorax, X-RAY, ADDITIONAL FINDINGS, INJURY, SCANS, MDCT
Kocaeli University Affiliated:
Purpose: The purpose of this study is to investigate whether the use of thoracic computed tomography (TCT) as part of nonselective computed tomography (CT) guidelines is superior to selective CT during the diagnosis of blunt chest trauma. | <urn:uuid:3db0c224-eb8f-4e1d-9506-1abd7f06598f> | CC-MAIN-2023-40 | https://avesis.kocaeli.edu.tr/yayin/ba00c666-e865-4b69-b715-0820dcfdc412/the-significance-of-routine-thoracic-computed-tomography-in-patients-with-blunt-chest-trauma | 2023-09-28T18:18:47Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.675314 | 272 |
Clicking on the icon will search the masterlist for characters with that trait!
This trait only applies to AW0001 Halo's and allows for,
- Halo's stacked inside of each other
- Halos intersecting with each other
- Hanging a windchime off of a halo - while this does apply to a windchime it is the only instance under which this trait would be used with one.
1 result found. | <urn:uuid:f0ced77a-ff16-428f-860d-0ce35a91bb54> | CC-MAIN-2023-40 | https://aw0005.com/guides/traits?name=Stacked%20or%20Connected%20Halo | 2023-09-28T16:39:32Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.881764 | 105 |
Welcome to WordPress. This is your first post. Edit or delete it, then start writing! Share Previous Post Few quips galvanized the mock jury box You Might Also Like Few quips galvanized the mock jury box October 20, 2016 A very bad quack might jinx zippy fowls October 20, 2016 All questions asked by five watch experts amazed the judge October 20, 2016 1 Comment A WordPress Commenter says: May 1, 2019 at 5:47 am Reply Hi, this is a comment. To get started with moderating, editing, and deleting comments, please visit the Comments screen in the dashboard. Commenter avatars come from Gravatar. Leave a Reply Cancel replyYour email address will not be published. Required fields are marked *Comment * Name * Email * Website Save my name, email, and website in this browser for the next time I comment. | <urn:uuid:df75b930-f3ae-46b0-b977-b211b95301bb> | CC-MAIN-2023-40 | https://babyngiggles.co.zw/2019/05/01/hello-world/ | 2023-09-28T16:36:35Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.918976 | 178 |
The relationship application market is flourishing, plus the ways for online dating apps have in no way been far more different. There are other compared to a thousands of options that can be found, and every one has its own special characteristics. Tinder, as an example, can be a terrific way to make new friends. But you must be very careful: not every going out with software are created equivalent. Some are just basic terrible, and some can help you find your perfect match. In this article, we shall take a look at three of the most widely used internet dating apps and reveal how to use them properly.
One of the most necessary feature of your relationship iphone app is the messaging functionality. Full-presented talk or perhaps in-app text messaging helps to keep customers about the base and prevents spammy, which may be a real trouble. Adding voice notices or video clip getting in touch with to the mixture can assist enhance the conversation. Prior to deciding to fulfill them face-to-face, it displays whomever that you’re secure talking to and wants to get the hang of them. Additionally it definitely makes the conversation additional total and fascinating.
In case you adored this article in addition to you desire to be given details concerning Asian Date Online kindly visit the web site.
Another crucial function is chat text messaging. It ought to be effective, although this is amongst the most straightforward specifications of an courting iphone app. A complete-showcased chat will allow users to convey conveniently and without having disruptions. You should also incorporate speech information and online video contacting to supplementation SMS sending text messages. This means that people can feel completely satisfied with additional guy prior to they meet up with physically. Using non-verbal communication could add a rich coating for the discussion.
The main reason why a dating iphone app must integrate conversation messaging is really because it retains people around the program. An mobile app that gives whole-showcased talk has the main advantage of becoming additional engaging than the usual written text-based iphone app. Additionally it permits people to utilize abundant media channels as well as a gamification tier. The best online dating applications in addition offer formidable authentication components. To ensure that end users can have confidence in each other well with hypersensitive details, the consumer user interface must be as basic as potential.
A internet dating iphone app need to have a talk function that engages end users and makes them inside the software. A user user profile is usually a key element of any courting app. Developing a unique individual profile is just about the most crucial attributes of a dating software. The conversation characteristic can keep customers interested, with wealthy mass media and gamification. The application also is offering a gamification coating. This is important to ensure that users can properly easy access facts.
A going out with mobile app should have an end user screen which causes the ability satisfying and helps to keep customers hooked. A online dating iphone app must have an individual account that is definitely both equally visually attractive and intriguing. A user information should be an essential part of the general knowledge and ought to be-designed for quick discussion and navigation. A stylish user profile will stimulate customers to engage along with the merchandise. With an user interface that may be either intuitive and fun is a wonderful feature for your courting application form.
The public area of dating is a valuable part of an prosperous courting app. A social-concentrated knowledge is very important for users. The application must have a superior-quality interface. XO is actually a pleasurable approach to connect to other individuals. Its gamification capabilities allow for persons to take part in discussion and meet possibilities date ranges. This function is vital since it improves the chances of a time frame. This feature is vital to get a internet dating support to enjoy a very good person experience.
Her is often a courting iphone app that is similar to Tinder. It’s a social network that joins consumers through their discussed pursuits. While Tinder is really a free of charge mobile app, Her is really a subscription-dependent service. It includes quality features for individuals, although it’s free to be part of. With high quality subscribers, you are able to check out profiles of local end users and satisfy them personally. Its user interface is essential on your good results. However, if you’re unhappy with the caliber of your match up, you should attempt some other online dating software.
A dating app’s consumer profile is its most vital attribute. It could comprise of a customer survey or it can be a thorough person description that allows the app to accommodate you with well matched persons. The person user profile can be as simple being a biography, or if you would like it to be. There’s a restriction to the amount details you should offer on your description, nevertheless, you don’t desire to be far too hazy. The greater amount of details you provide the better.
For more information regarding Www.Asiandate.online stop by the website.
Should you be serious about the content in this post, below are a few a lot more web pages with a similar content: | <urn:uuid:2f57aa7c-100e-4222-833a-bd6e1fe77784> | CC-MAIN-2023-40 | https://bagrentalvacation.com/6575-the-essential-options-that-come-with-a-dating-app-25/ | 2023-09-28T17:50:56Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.943206 | 1,059 |
Yoga can be an historical process ofpsychological and strict, and bodily methods. It aspires to soothe the brain and handle its pursuits. The practitioner can recognize a separate ‘witness-consciousness’ that is free of thoughts things to do and tedious suffering, by practicing yoga and fitness. The mind’s pastime is actually a diversion from unwanted feelings. Yoga can certainly help one get a express of’stillness’, by emphasizing this. This condition will allow you to experience the ‘ultimate bliss’.
Based on age-old Indian history, the term yoga exercise practically suggests “to combine.” It attempts to unify unique expressions of living on the greatest actuality. These specific symptoms, which can be only area pockets of your primordial seaside, are caused by the development approach. The grape shrub, the pear hardwood, along with other sorts of life all jumped from your exact same the planet. The final purpose of pilates is to feel the dynamics of lifestyle as well as know the cause of all of that is.
For the reason that statement implies, yoga demands the partnership from the imagination and the body. In a program of yoga exercises, we really should notice our individuality and our gathered staying. The era of the yoga exercises can also help us be associated with people. Accomplishing this union permits us to experience everyday living in the deeper place. So, we can apply the exact same yoga exercises techniques that other people do and establish a greater perception of our individuality.
The term “yoga” means “what delivers that you fact.” It literally indicates “partnership” and is meant to enable folks understand their particular ultimate nature. When formation, specific manifestations are surface air bubbles and the closing fact is 1 with the full. The skin, for example, as well as pear tree, all originate from a similar world. Through pilates, we proceed when it comes to the experiential truth of existence, or your own substance.
The fundamental cause of the phrase “meditation” is unstable, nonetheless its title hails from the Sanskrit words asia. This has been used for hundreds of years to show spiritual techniques and wellbeing. The first regarded mantras inside Vedic vocabulary are “Aum” and “Om”, which may have symbolic symbolism in a range of nationalities. There are various adaptations with the concept, which include varied types the exact same word. Some evidence indicates that it’s connected to several health and fitness benefits, such as a reduction in cholesterol, even though of such mantras do not have literal this means, while others can be much more abstract, which include ‘Om’.
The beginning of yoga and fitness are cloudy. It’s also worth noting that pilates has lots of gains for that human brain, mainly because it is affecting the endrocrine : glands. One’s body has various performs. It is considered to control the secretion of several the body’s hormones. Thus, you should learn the best way use mantras.
The domain name of yoga and fitness derives from the word what “partnership”. It refers that the the consumer manifestations of life, when they are mango bushes, avocado timber, or individuals, are generally air bubbles that put their hands up from your similar globe. Because of this, the dhyana mudra, a symbol of your greatest actuality, is often a impressive religious apply that can bring of a deeply and lasting un. It’s a form of meditating to help persons accomplish that condition of remaining.
Along with meditating, pilates also involves a meditation express. The meditative point out enables you to definitely attain if you’re an of focus and concentration. This is successfully done by concentrating on a unique sound. It is essential to target someone’s air, simply because it decides the grade of the knowledge. The meditation way of thinking is really important for acquiring a relaxing natural environment. An attractive mind-set will help you to go through the planet.
The meaning of “yoga and fitness” is usually a metaphor for fact. The idea of pilates is a “partnership” between personal and the best. This would mean burying opinions and concepts, and becoming thoroughly human being. The era of the yoga and fitness is the key to repeating this frame of mind. The eventual condition of mind is “unity”. It’s possible to explain their very own id for being, therefore build a route toward real partnership while using the universe.
Here’s more information about https://courses.onlineyoga.school/pages/blog?p=what-is-accessible-yoga-and-why-is-it-important review the web site.
More recommendations from highly recommended editors: | <urn:uuid:ac48fb2f-2086-4fc6-a14f-8fb7439ec3ef> | CC-MAIN-2023-40 | https://bagrentalvacation.com/8345-yoga-101-what-exactly-is-yoga-53/ | 2023-09-28T17:17:07Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.945836 | 1,017 |
These days, you will find a numerous cannabis rewards more and more men and women are acknowledging. Although this grow has actually been traditionally used for millennia, it was only just recently that many people are taking the dive into introducing it in their standard day-to-day lives. This is not astonishing when you consider the enormous range of probable health care added benefits that range from usage of cannabis. Furthermore the cannabis place have a long reputation being utilized as medicine, yet it is also quite a novice to the healthcare marketplace. Because of this, it is essential that you simply do not ignore most of the excellent possibilities that marijuana offers.
One of the greatest attributes of marijuana is it is really a natural, simple fix for a whole variety of ailments and ailments. The usage of marijuana extends back to the 7th century BC in early Egypt. There, it was actually utilized to relieve fevers and handle drinking water retention, while making an effort to alleviate pain and irritation. Even though it is still widely used now, it truly is starting to be more recognised that it could supply numerous health advantages.
Typically the most popular form of cannabis is health cannabis. It is frequently located in Colorado and expands somewhat extra tall, getting to approximately 18 ins or thereabouts. Health marijuana is prescribed by health professionals to people that are suffering with a number of health conditions. One example is, it is usually approved that will help affected individuals affected by glaucoma, an eyeball disease that brings about loss of sight. Many other ailments can also be paid by a sound health-related marijuana doctor prescribed.
Along with health marijuana, there is also a selection of diverse stresses and types of cannabis that are used for several reasons. Involving these kinds is bud, the cannabis plant’s reduce, weakened, leafier nephew. The bud includes a channel, sugary flavour and is also normally included in cooking. This is the sort of cannabis that is definitely frequently available at the local market. Even so, it is very important note that you must take in bud adequately, or it could have unhealthy side effects.
Cupcakes, desserts and brownies can also be widely used pleasures made with cannabis. These goodies are excellent for many distinct causes. They feature a top through the marijuana without the need of introducing any sweets, making them ideal for diabetes sufferers. Also, they offer a simple solution to add cannabis into one’s eating habits without having putting unwarranted pressure or stress to your diabetic.
One more easy way to integrate marijuana into your meals are by employing infused butter. Can be infused with some other things such as vanilla flavor, maple syrup, peanut butter or perhaps bare bee honey, even though this is commonly purchased in its fresh variety. These infused butter recipes have become popular as time passes as everyone has recognized how delectable and beneficial they might be. These recipes typically get started to be a much easier butter recipe but could be converted when hot to make several unique recipes. Many of the very popular infused butter tested recipes consist of: glazed banana cupcakes, butterscotch green tea, peanut fragile, and sugar-cinnamon toast.
One of several final cannabis benefits to message is but one that lots of people today disregard. That profit is the simple fact that cannabis is among the most robust natural cures to choose from. It really has been applied for hundreds of years for a medical solution for a variety of professional medical conditions including cancers and HIV/Helps. They also have arrived at be aware of the huge selection of other health advantages it may present towards the consumer, while today, scientific study has not only learned the benefits of cannabis for treating these ailments. Right here are some of the other health advantages of marijuana:
As you can see, the many benefits of marijuana are extensive. It is essential that patients who are suffering from diabetes must not discount marijuana completely. Fairly, they ought to discover how to integrate it to their day-to-day schedule. When taken in right quantities, it may deliver great benefits to any diabetic person patient. Learning about these added benefits and using them into one’s everyday regular could eventually resulted in a far more better and comfortable everyday life for a person who is affected with this problem.
If you loved this short article and you would want to receive more info relating to https://420maryjointusa.com assure visit our webpage.
A lot more ideas from recommended editors: | <urn:uuid:da840344-c063-4708-bd00-90fea169ba50> | CC-MAIN-2023-40 | https://bagrentalvacation.com/9679-can-you-gain-benefit-from-the-medical-benefits-of-cannabis-for-having-diabetes-33/ | 2023-09-28T18:21:51Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.971225 | 897 |
So You Want To Get Into Woodworking? Setting The Foundation.
By Anna Bailey
So you’re thinking about getting into woodworking, but aren’t sure where to start?
You’ve come to the right place. We happen to think that woodworking is one of the most rewarding and fulfilling hobbies that you can invest your time and energy into. It doesn’t take a long time to learn the basics. With continuous improvement, you might even find that you enjoy it so much that you’d like to use that passion to create a product line for a family business.
With so many options, it can be hard to decide what the right products are for you. There is a wide range of general woodworking tools out there, so deciding where to start depends on what your interests are. With any new venture, practice will guide you to what you discover you enjoy the most. To help you explore the world of woodworking, I will share with you what I believe are the top tools to get started on any woodworking project.
Before I go into what tools I think are important when starting woodworking, I thought it might be helpful to give you a few tips on what to look for when you go to purchase new tools.
In North America, we are presented with so many options and brands to choose from in practically every type of purchase that we make, that it can become really confusing to decide which product will be right for you. I don’t believe that one single brand name is going to be the best because there are so many high quality woodworking tools available. And when you are just starting out, you might not want to invest in the highest quality products until you know that woodworking is something you want to stick to.
I really suggest, when making your purchasing choices, to have a nice balance between high performance and superior value. Check for each manufacturer’s warranty terms and safety standards, and read reviews to determine the reliability of their products. It is also good to be aware of their product support resources.
When starting out, don’t forget the importance of well working and precise hand tools. These are the foundation to accuracy and solid building. Make sure you have a tape measure that works well for you. When purchasing a new tape measure, I always make sure to buy one with the included micro measurements numerically written in for quick reading.
Disclosure: Some of the links below are affiliate links. This means that, at zero cost to you, I will earn an affiliate commission if you click through the link and finalize a purchase. As an Amazon Associate I earn from qualifying purchases.
You will also need a good square, to make sure you are getting consistent and accurate measurements for angles. Much success can be had when you have the right foundational tools in your toolbox.
Pro tip: Pencil holders are super helpful to clip onto your apron so you always have one handy! They are affordable and totally worth it.
When purchasing a new hammer, hold it in your hand and make sure the weight of the hammer feels comfortable for you to strike with. Another tool that can be useful is a rasp, when you need to make adjustments that require more effort than purely sanding.
When getting into woodworking machinery, there are so many options. My suggestion is to start simple, and build your kit as you go.
There are, however, some fundamental power tools that add extreme value when it comes to saving time and increasing accuracy. Again, it really depends on what type of woodworking you are planning on doing. If your projects are small, there are some tools you can live without, especially when you are starting out.
Regardless of the size of the project, you will need a method for cutting your wood materials.
Most small, straight cuts can be accomplished most efficiently with a miter saw.
A miter saw allows you to make quick, straight cuts in any angle or bevel that is needed. The width of the wood you are able to cut depends on the size of the miter saw. Some miter saws have a gliding arm to allow for wider cuts.
Many projects require curved cuts. These cuts can be accomplished with a jigsaw.
Jigsaws are a very reasonable tool to add to your kit that allows for great versatility. If working decoratively with fine detail, your best bet is to look into a scroll saw. Scroll saws allow you to make intricate cuts that embellish a project, and is a great tool to expand on your creativity.
Most projects will require you to make long straight cuts. In a pinch, you could use a jigsaw to accomplish these cuts. However, you will get much cleaner cuts with more precision if you use a table saw.
Another option, though also not as easily accurate as a table saw, is the use of a circular saw. Circular saws are hand held and can move through sheets of wood effortlessly. You can help with the accuracy by using guides that run alongside your wood to encourage an accurate, straight cut.
Another cutting tool that I find to be extremely useful and versatile is the oscillating tool.
Oscillating tools have many different uses, and many different attachments for the application you are using it for. Aside from general woodworking, they are super useful for house projects.
As your love of woodworking grows, you might find that these saws will suit all of your needs. You also might want to consider other saws such as band saws and cabinet saws. A lot of this will depend on your available workshop space.
You might consider the purchase of an air compressor, as this plays a vital role in the use of several tools that require air pressure as their power source. Having an air compressor on hand will make quick work of projects that require nails, with the use of a pneumatic nail gun. An air compressor can also be used for applying stains and paints.
The last essential item that must be mentioned is a wood sander.
Wood sanders are used for so many purposes throughout the creation of a wood project, and there are many to choose from.
Drum sanders are used to remove wood layers rapidly and are very aggressive.
Belt sanders can also be used to sand off layers of wood quickly and evenly from flat surfaces.
For a simple, portable sander, I would consider the use of a random orbital sander. These sanders fit in the palm of your hand and work very well for smaller projects. I also appreciate them when working around outer corners.
Hopefully this list of my top tools to get started in woodworking has given you some ideas to consider when setting up your woodshop.
This list of tools will set a good foundation for any type of woodworking project that you are hoping to pursue. Don’t forget to enjoy the process as you use this creative outlet for enjoyment, and even as a source of income. | <urn:uuid:8b0ba634-e5c3-454d-932a-2f726f16d5af> | CC-MAIN-2023-40 | https://baileybuilds.blog/2022/05/27/top-tools-to-get-started-in-woodworking/ | 2023-09-28T17:14:25Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.960436 | 1,435 |
- 1 cup Crown® Lily White® Corn Syrup
- 1 cup sugar
- 1 cup creamy peanut butter
- 6 cups crispy rice cereal
- 1 cup semi-sweet chocolate chips
- 1 cup butterscotch chips
- 3/4 cup crushed peppermint wheels OR candy canes
- Cook corn syrup and sugar together in a large saucepan over medium heat, stirring to dissolve sugar. Bring mixture to a boil. Remove from heat. Stir in peanut butter; mix well. Add cereal; stir until evenly coated.
- Pour into greased 13 x 9-inch pan and pat into place.
- Melt chocolate and butterscotch chips together in saucepan over low heat, stirring constantly. Spread over cereal. Sprinkle on crushed peppermint candies.
- Cool at least 45 minutes, or until firm. Cut into bars. | <urn:uuid:8770aba6-8601-4eea-9ea7-329570ac62b6> | CC-MAIN-2023-40 | https://bakegood.ca/baking-recipes/festive-peppermint-scotcheroos/ | 2023-09-28T17:16:50Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.787235 | 186 |
I first visited Valencia in 2007 during the America’s Cup boat races. Given that I was a young backpacker who was traveling with friends at the time, that trip was more focused on the party scene Valencia offers than its amazing architecture, culture, and food. Therefore, during my second visit to Valencia in 2013, I planned to experience more of the city’s tourist attractions and embrace the Valencian lifestyle as best I could.
To get to Valencia from Madrid, we decided to take an express train. From the Madrid airport to Atocha train station I took a yellow express bus which cost 5€ and took approximately 40 minutes. Sara was waiting for me at Atocha and had already purchased tickets for the express train to Valencia. Spanish trains are generally wonderful with clean and comfortable cars and fast journey times, especially on the express services. Unfortunately, this excellent service often comes at a cost as train travel is rarely cheap in Spain, although sometimes there are discounts available by booking in advance or taking advantage of other offers. After traveling at speeds of over 200km per hour for most of the way, we made it from Madrid to Valencia in only two hours. Upon arrival, Sara called her brother Javier who lives in Valencia with his girlfriend Marta and we made our way to their apartment.
In true Spanish fashion, Javier had prepared a wonderful tortilla (thick egg and potato omelette) for us to enjoy upon arrival. After the delicious dinner it was time to get some rest given I’d had a long day of plane, bus, and train rides.
The next day, we all went into Valencia’s old town for lunch. Sara and Javier showed me the many buildings in the old town and we found a place for lunch where I tried Valencian paella. Paella originated in the mid-19th century on a coastal lagoon in Valencia. While there are many variations of the dish throughout Spain, Valencian paella is the original. The flavourful dish traditionally contains white rice, green vegetables, chicken and rabbit meat, land snails and butterbeans, all cooked in olive oil and seasoned with rosemary, saffron and sweet paprika. In many restaurants in Valencia the chefs will bring the paellera (cooking dish) right to the table so you can eat straight from the dish in traditional style, but my paella was simply plated.
Lunch in Spain is traditionally the largest meal of the day and there was no better way to digest it than to go walking through Valencia’s main city park which was conveniently built in the old Tùria river bed. The beautiful thing about having a river bed for a park is that it winds its way all through Valencia and provides a wonderful place for recreational activities and art displays.
As the sun set, we walked back to Javier and Marta’s apartment for yet another amazing meal for dinner along with a couple of beers. In true Spanish fashion, we then set out to the bars around midnight. Mixed drinks in Spain are not necessarily as cheap as I had thought as we were paying 5-8€ for each highball, but the drinks are strong and free-poured making them relatively inexpensive compared to other cities internationally. The thing I love most about Spanish bars is the atmosphere as the music is always played at a level that still allows for socializing and the interior designs are usually unique and fun. At 4am, the bar we were at closed which meant heading to an after-hours club that would stay open until the early hours of the morning. We ended up at what I would call a Spanish Classic Rock bar, and they played songs that were the Spanish equivalent to Guns N’ Roses, Green Day, Aerosmith, and the Rolling Stones. Although I did not understand the lyrics, the guitar riffs and music was excellent and I enjoyed seeing Sara sing along to hits from her youth. By 6am, we all began slowing down and walked back to the apartment for a late sleep-in, but I could tell that many others would still be dancing after the sun came up. The Spanish definitely know how to have a good time!
When we finally woke up and had lunch it was already mid-afternoon and Sara and I had not yet explored the City of Arts and Science, a multi-plex of beautifully designed buildings in Valencia. Although we were within walking distance of the area we decided to take advantage of Valencia’s wonderful public bike system. The city provides bike racks around the city where users can borrow bikes, commute, and leave them in the next available bike rack. Luckily, Javier and Marta had cards for the bike system so we were able to quickly borrow the bikes and get to the Science Museum in time to spend a couple of hour looking arounds. There are numerous ticket options and Sara and I chose a combination Science Museum / Hemisfèric ticket for 12.60 € each. The Hemisfèric is a theater with a round 180° screen that plays movies all around you. As we wanted to maximize our time visiting the Science museum, we chose an 8pm film which would give us an hour to explore the Arts and Science complex after the 7pm museum closing.
The Science Museum was a lot of fun as many of the displays were interactive and interesting. The museum is also very large, and even with 2-3 hours to explore Sara and I were unable to explore all of the exhibits. I especially enjoyed the interactive exhibits, many of which creatively demonstrated basic physics, and a health and body exhibit that had measurement devices for strength, foot size, stability, etc. At 7pm, the museum staff began forcing us out of the building, but the timing was perfect as the buildings of the City of Arts and Science were bathed in beautiful light from the setting sun. I would highly recommend watching the sunset in the area as the architecture appears to change greatly as the lighting conditions vary.
Outside the Science Museum, Sara noticed a stand selling horchata, a drink originally from Valencia that is made from tigernuts. Although I was skeptical about the drink since it resembled flavoured soy milk, when Sara had me try it I was delightfully surprised. The horchata was served cold and was both sweet and refreshing in the warm Valencia weather. Wishing I had purchased a horchata for myself, Sara and I wandered the ‘city’ taking photos of the beautiful architecture and waiting for our film to begin. I have always been very impressed by Spain’s historic architectural designs, but Valencia proves that the Spanish are just as successful at constructing unique modern buildings. Each building making up the City of Arts and Science is unique and aesthetically pleasing, making it a beautiful area to walk around and explore.
At 8pm our movie in the Hemisfèric began. Although I was concerned my Spanish skills were inadequate to understand the movie, luckily everyone was provided with multi-lingual headsets which allowed me to listen to the film in English. The film was called “The Last Reef” and was a pretty depressing account about how the world’s reefs are being destroyed. The video within the film was excellent and made me eager to go diving again as soon as I can. After the movie was finished, the sun had set and the City of Arts and Science was beautifully lit making it a perfect opportunity for more photographs.
Sara called her brother and we decided to meet for tapas near city center given that it was Sara and my last night in Valencia. Once again, Sara and I borrowed bikes from the public racks and rode along the river park into town where we met Javier and Marta. I love Spanish tapas as it creates a social meal full of many flavourful and unique dishes. After dinner, we walked back to Javier and Marta’s place, but not before stopping for an ice cream for dessert. The previous day, Sara had showed me an ice cream stand that had every flavour of ice cream you can imagine including olive, pumpkin, smoked salmon, cod fish, and my personnel choice of Red Bull. Sara was underwhelmed by her pumpkin ice cream, but I thoroughly enjoyed my Red Bull flavour as it tasted just like you would expect it would.
After a wonderful sleep and a quick farewell to Javier and Marta, we set off for Valladolid, where Sara had to work in the evening. I thoroughly enjoyed Valencia and believe it is a wonderful city to both live and travel. I hope to return one day soon to further explore the City of Arts and Science, including the famous Oceanografic aquarium, and also see some of the nearby beaches. | <urn:uuid:2a92885b-a3a1-4371-8756-1c5eef02103a> | CC-MAIN-2023-40 | https://baldpacker.com/spain-valencia-arts-science-food | 2023-09-28T17:54:36Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.981056 | 1,774 |
Inmates at a St. Louis jail rioted on Saturday morning over a variety of concerns, setting fires and throwing debris to the street below as corrections officers worked for almost eight hours to end the “extremely violent” group.
The riot at the St. Louis City Justice Center ended shortly before 10 a.m., but only after the prisoners had spent hours throwing a stationary bike, chairs, mattresses and other things to the streets below, some of the items burning.
Dozens of people gathered to watch the riot and efforts to contain it. Flames could also be seen just inside the windows.
“Even though our automated P.A. system would indicate that the cells are locked, they are in fact not locked and so other detainees were able to get out of their cells and into the unit,” St. Louis Public Safety Director Jimmie Edwards told KDSK.
Corrections officers used tear gas to regain control and had all 115 inmates involved in the riot back in custody.
The inmates claimed that they were fed up with conditions during the coronavirus pandemic, as well as a series of restrictions that limited visits and stalled court proceedings, officials said.
Dozens of inmates had already been transferred from the City Justice Center after two disturbances in late December and early January, making this the third such disturbance in a very short time.
“There are some burn marks on the front of the building. They destroyed the inside of their floor and threw all sorts of stuff outside. … They flooded the floors, clogged the toilets, clogged the drains, so there is water damage,” said Jacob Long, a spokesman for Mayor Lyda Krewson.
The riot started around 2:30 a.m. after an inmate and a guard scuffled and the guard was jumped by other inmates, St. Louis Today reported.
Jimmie Edwards, the city’s director of public safety, told reporters that the corrections officer was injured and taken to a hospital. That guard suffered bruises and contusions and was released later in the day.
No other officers or inmates were reportedly injured.
The corrections facility is located on the fourth floor of the Justice Center, with only glass windows facing onto the city street and no fencing or additional barriers around the building.
Fox News reached out to the St. Louis City Justice Center and St. Louis Police Department for comment, which is pending.
The Associated Press contributed to this report. | <urn:uuid:bd14921b-e639-46ed-9959-dfc736c2cdb4> | CC-MAIN-2023-40 | https://balthazarkorab.com/inmates-at-st-louis-jail-set-fire-destroy-windows-for-third-time-in-weeks/ | 2023-09-28T16:48:17Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.977014 | 507 |
Invest in Reliable Termite Treatment
A home is a great investment in itself, but it’s easy to forget that keeping up with your home is another ball-game. Bama Pest Control, Inc. knows that termites can get the best of you, which is why we offer two types of termite treatments that allow for your home to rid of its termite problems. If you’re unsure whether Bama Pest Control, Inc. is right for you, ask yourself this: Why choose between one treatment when you can be more thorough and have two? Most pest companies are solely interested in the dollar that their treatments bring them, but Bama Pest Control, Inc. has the interest of your home and safety in mind.
All our service professionals are trained in the leading termite control methods and can provide the entirety of termite control options like baits, poison and treat, monitoring stations, and more. | <urn:uuid:4abf4e44-ab76-4039-9362-511c82a22c50> | CC-MAIN-2023-40 | https://bamapestcontrol.com/service/termite-control/ | 2023-09-28T18:41:49Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.951406 | 192 |
We have a sweet spot for cupcakes. And the women who defy all odds to make them their livelihood.
In 2008, Melissa Ben-Ishay lost her job in advertising. Thank goodness her brother was a believer in the power of positive baking. With his enocouragement, Melissa turned her hobby since childhood—making bite-sized baked goods—into a full-time pursuit. NYC-based cupcakery Baked By Melissa was born and she’s never looked back.
A sweet success story, Baked By Melissa now exists in 13 locations, including JFK’s JetBlue Terminal 5. The menu includes an array of inventive cupcakes, cookies and macarons, but she also founded the ‘cupcaron’, a cupcake-macaron hybrid in fleeting seasonal flavors such as strawberry cream, chocolate graham and cotton candy. We admire Melissa’s creativity, ambition and stylistic innovation. We are honored she’s a part of our TURN IT campaign with PopSugar, which spotlights women who’ve pioneered a bold path toward positive change.
They say at any given time, you’re one decision away from turning your life around. The proof’s in the pudding. Or, this time, the cupcake mix. | <urn:uuid:89f6ad01-5056-49cd-88a8-0a69764359be> | CC-MAIN-2023-40 | https://bananarepublic.us/2017/05/01/live-deliciously/ | 2023-09-28T17:04:07Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.942675 | 273 |
Hailing from London, 19 year old singer Arlo Parks advocates the visibility of a community that’s quickly rising to relevance. Her voice is beautifully deep and smooth, complementing lyrics that speak to and of those around her perfectly.
Although melancholy, the melodies are comforting, taking inspiration from a wide array of influences, including the poet Sylvia Plath. And though she describes her sound as both fluid and textured, once you hear songs like ‘Paperbacks’ and ‘Sophie’, you’ll see how it all makes sense.
Banger was able to catch up with her on the importance of her lyrics, her interest in poetry and where to see perform next.
Interview by Ellie Rose
Words by Kieran Mehra
Photos by Charlie Cummings
For the people that don’t know you, can you introduce yourself and describe your sound in 3 words?
I’m Arlo Parks, I’m 19 years old and I’m an artist/poet from London. Fluid, emotional, textured.
What have you been working on recently?
I’m working on the album.
Do you think you’re in a ‘super sad generation’?
I would say so yes - I wrote that song about the people around me.
There is some obvious crossover with poetry and songwriting, does writing lyrics come naturally to you?
It’s the most natural thing in the world - words just make sense to me.
You said you’d one day like to release a book of poetry— what, to you, distinguishes a poem from a song?
I would say a poem could exist without any kind of instrumentation - the line between them is very blurred though.
Would you consider songwriting more of a form of introspection, or do you see yourself as a voice to speak to the outside world?
It’s both - I write songs for me but hope that the outside world connects to them.
How important do you think Soundcloud is as a platform?
Very important - it allows for connection and experimentation - I was on there all the time when I was younger just reaching out to people and discovering niche music.
Make us a rhyme about the word ‘Bang’?
Im answering questions for bang(er)
Because of the records I sang
Do you ever get nervous performing on stage?
I always get slightly nervous but as soon as I start the first song the nerves evaporate.
If you had to pick one artist you take influence from the most, who would it be?
What was the best gig you’ve ever been to?
Loyle Carner at Shepherd’s Bush 02
People have pegged you as the voice of Generation Z, do you agree?
I guess I’m trying to speak up for people but there can never be one voice that represents a whole generation with so many unique individuals.
What's your favourite lyric you’ve ever written?
Do you remember when you broke your arm tryna climb your way to paradise?
As a London local, what are the city’s most underrated venues to catch basement gigs?
When can we next see you perform?
I’m doing a headline of the UK/EU in February and March which ends at Hoxton Hall in London. | <urn:uuid:f61422a3-2f69-4479-9f4c-7904433f37be> | CC-MAIN-2023-40 | https://bangermagazine.com/Arlo-Parks-1 | 2023-09-28T18:26:55Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.961496 | 719 |
Sprout Media Lab is a full service web design and digital marketing agency with offices in Raleigh, North Carolina, and Ormond Beach, Florida. They approached bant.io because they needed a more scalable and sustainable way to build leads across the North Carolina and Florida areas.
Sprout specialises in smart, effective and affordable marketing solutions that are designed to help companies to boost their Google rankings, increase their website traffic and to generate more leads. This meant that they already had a thorough understanding of the basic concepts behind what we do, which allowed us to focus on getting the messaging right and narrowing down the target audience.
While starting with proven strategies we also ran multiple experiments on messaging and data, reaching 4,359 prospective clients and generating 46 hot leads for Sprout Media Lab to date. We augmented this by deploying two different email sequences and four A/B tests, as well as a strategic LinkedIn outreach campaign which generated six opportunities, all of them being based in the target markets.
Sprout Media Lab approached bant.io because they needed to supplement their sales funnel with leads from North Carolina and Florida.
- 4359 prospective clients reached
- 2 email sequences developed
- 4 A/B tests performed
- 25% Open Rate
- 35% Response Rate
- 16% Conversions to Opportunities
- 46 Hot Leads | <urn:uuid:9ae722a0-09fa-4b53-a099-2f2b5c63bbfe> | CC-MAIN-2023-40 | https://bant.io/case-studies/sproutmedialab | 2023-09-28T18:07:27Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.946725 | 283 |
BHH member Pallapupas, thanks to the collaboration of BHH member Robin Hat, launches a limited Christmas edition of its socks. After more than 7 years of collaboration and relationship, Robin Hat has decided, once again, to do its bit for the organization through the design and manufacture of a solidarity product. The profit from its sale will go entirely to Pallapupas, in order to fill hospitals with laughs this Christmas.
Javier Garrido, co-founder and CEO of the company, emphasized that “it is a pride to collaborate with Pallapupas once again because of the deep admiration we feel for the work they carry out daily in Hospitals and Health Centers.” Pallapupas and its task are essential in Hospitals and we hope that people will join this campaign and raise a lot of money to make the presence of Pallapupas even greater.
For her part, Victòria Vicens, a member of the Department of Sensitization and Recruitment of Pallapupas, has pointed out that “our objective is to improve the emotional state of patients, relatives and personal health, and to take special care of them in an era of a sensitive and fragile era like Christmas. We are delighted and pleased to be able to count on Robin Hat, a company with who we have shared values and a relationship for years, made up of people who put emotional care first and help us bring smiles in hospitals.”
Get their socks in their charity shop and help their mission here! | <urn:uuid:791672f4-7de7-484a-90da-300f6709c3f5> | CC-MAIN-2023-40 | https://barcelonahealthhub.com/news/2022/11/18/pallapupas-robin-hat-launch-limited-edition-christmas-socks-bhhmembersinitiatives/ | 2023-09-28T18:56:46Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.968721 | 314 |
What happens with English Wills applying to Spanish assets?
As pointed out in some of our articles and videos, it is generally advisable to have a Spanish Will for your Spanish assets than having an English Will (or a Scottish Will) that covers your worldwide estate. However, very often we find ourselves dealing with Spanish estates where the deceased died with no Spanish Will. In those cases, if there is a general English Will, then this one can be used for the assets in Spain. However, the English Will is not sufficient to administer the Spanish estate. It is also necessary to have a Grant of Probate that validates the English Will and confirms the appointment of the Executors.
The Spanish Land Registrars are now familiar with this document and have started to request the Grant of Probate whenever there is an English Will involved. This can become a problem in estates where the deceased died with an English Will but no Grant of Probate was issued as all his or her assets were in joint names with the spouse. From an English law point of view, there is no need to obtain a Grant of Probate if the deceased had no assets in his sole name but the Spanish Land Registrars are not aware of this fact and will still request a Grant.
What can be done in cases like the one above? One option is to apply for a Grant of Probate but this will not be a straightforward process as, technically, there is no need to get one. It is very likely that the Probate Registry will ask all type of questions and will want to understand the reason why a Grant is required. This can prove costly and time consuming.
Another option is to issue a certificate of law in Spanish for the Spanish Authorities explaining why the Grant is not required and also clarifying who the beneficiaries and executors of the estate are. The norm is for this document to be drafted and signed by a Notary Public or a Solicitor who is familiar with both legal systems.
As usual, there is always a solution to a problem. The important thing is to instruct the right professionals and, why not, also have a little bit of luck. | <urn:uuid:3a14082c-86ac-4706-a6be-71feb46ea6af> | CC-MAIN-2023-40 | https://barcelonasolicitors.com/english-wills-for-spanish-assets-why-the-land-registrar-requires-a-grant-of-probate/ | 2023-09-28T18:47:28Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.976293 | 436 |
Peregrine 1 juvenile female.
Golden Plover 8. Skylark 25. Fieldfare 234. Redwing 104. Song Thrush 1.
alba Wagtail sp. 2. Meadow Pipit 101. Linnet 9. Goldfinch 131.
Going south west:
Wood Pigeon 6460. Reed Bunting 3.
Lapland Bunting 1 calling! Pink-footed Goose 40. Starling 510.
Blackbird 1. Mistle Thrush 2. Lesser Redpoll 1. Siskin 1.
The day started well, with a calling Lap Bunting west!
Wood Pigeons got going well enough for 45 minutes, but then more or less packed in before 8am!Good Meadow Pipit count for the time of year and best Goldfinch of the autumn! | <urn:uuid:8726c2ba-b655-48cb-abd1-c7e975bed3a6> | CC-MAIN-2023-40 | https://barnsleybirds.blogspot.com/2022/11/wintersett-vismig-02112022.html | 2023-09-28T18:49:12Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.734108 | 182 |
A “whiteout” is meteorological condition in which snow falling from the sky and snow whipped up from the ground is whirled by a gale into a disorientating blanket of whiteness in which there are no visual bearings and it is all but impossible to navigate. It is an apt metaphor for the blizzard of coronavirus regulations which have cascaded out of Whitehall (and of course Cardiff and Holyrood too) since March. A search of the www.legislation.gov.uk website reveals a mind-boggling 133 (albeit each Welsh regulation is counted twice in English and Welsh versions) separate pieces of UK legislation, nearly all of them statutory instruments. Thus we have such delights as the Health Protection (Coronavirus, International Travel) (Amendment No. 7) Regulations, The Health Protection (Coronavirus, Restrictions) (Leicester) (Amendment) (No. 2) Regulations 2020, The Health Protection (Coronavirus, Restrictions) (Blackburn with Darwen and Bradford) Regulations 2020 and so on. And on and on. It is enormously difficult to find ones bearings amidst all these constantly changing rules and regulations. As David Allen Green put it on August 14th:
“There is not a lawyer or police officer in the land who any longer knows what is legal and not legal under coronavirus regulations. An absolute mess of a legal regime.”
Since August 14th matters have only got worse.
It is not often that I have much sympathy with Jeremy Corbyn’s weather-forecaster brother Piers (or to give him his own rather baffling description “LongRange WorldLeading weather+climate forecaster BIEuUsa. SolarLunar Method NotCO2! AmericanThinker Climate Predictor2010. Bro #JC4PM”), or with any of the anti-vaxx, Qanon, and 5G conspiracists who participated in a rally against masks and coronavirus restrictions in Trafalgar Square on Saturday 29th August. As well as Mr Corbyn, they included the antisemitic conspiracy theorist David Icke and a small group who deployed a flag remarkably similar if not identical to that of the British Union of Fascists. These are not easy people to like, although no doubt there were some more reasonable folk amongst them as well.
Nevertheless the £10,000 Fixed Penalty Notice issued to Piers Corbyn as someone “involved in” the demonstration is disturbing. Mr Corbyn’s “FPN” requires him – strictly speaking one could argue it “invites him” but it is an invitation backed by a threat – to pay £10,000 for breaching Regulation 5B of The Health Protection (Coronavirus, Restrictions) (No. 2) (England) Regulations 2020, as amended.
Regulation 5B was hastily made law last Friday 28th August, the day before the demonstration was held. It was introduced under an emergency procedure and was neither debated nor given even the most cursory scrutiny by any Parliamentary process. It permits the most junior Community Support Officer in the country to issue a Fixed Penalty Notice to the suspected organiser of a political event, demanding £10,000 to avoid prosecution and consequent financial ruin. Given its timing, even if it was not introduced with the purpose of targetting the organisers of a political protest against government policy, it very much has that appearance.
All the relevant coronavirus criminal laws – the lock-downs national and local, the closure of businesses, the requirements to wear masks, to quarantine and so on – have been created by statutory instrument. (The Coronavirus Act 2020, though the target of much misdirected criticism, is largely irrelevant). For readers with legal knowledge I apologise for stating the obvious, but a “statutory instrument” is a law made not by Parliament, like an Act, but by a Minister under a delegated authority given by an Act of Parliament, the “parent Act.” In this case the parent Act is the Public Health (Control of Diseases) Act 1984, S.45C of which, gives the Minister of Health powers to make regulations:
“for the purpose of preventing, protecting against, controlling or providing a public health response to the incidence or spread of infection or contamination in England and Wales (whether from risks originating there or elsewhere).”
These powers include [S.45C (3) (c)]:
“imposing or enabling the imposition of restrictions or requirements on or in relation to persons, things or premises in the event of, or in response to, a threat to public health.”
Particularly relevant to Mr Corbyn’s fixed penalty, these restrictions can include [see S.45C (4) (b)]:
“a prohibition or restriction relating to the holding of an event or gathering.”
There are limits to the regulations that can be made. Under S.45D:
“Regulations under S.45C may not include provision imposing a restriction or requirement by virtue of subsection (3)(c) of that section unless the appropriate Minister considers, when making the regulations, that the restriction or requirement is proportionate to what is sought to be achieved by imposing it.”
The “appropriate Minister” is Mr Hancock, and he has dealt with that somewhat fatuous requirement by including within the preamble to the regulations the statement that he considers that they are indeed proportionate to what he seeks to achieve (“a public health response … to the threat of SARS-CoV-2 in England”).
A general challenge to the lawfulness of the regulations was rejected in Dolan v. Secretary of State for Health and Social Care EWHC 1786, although the unsuccessful applicants in that case have since been given leave to appeal. Although I over-simplify, Mr Dolan argued that the regulations were outside (“ultra vires”) the powers delegated by the 1984 Act, and that they were incompatible with various rights under the European Convention on Human Rights, such as that to a private and family life and the right to associate.
The lawfulness of the 28th August amendments to the regulations which gave rise to Mr Corbyn’s FPN has of course not yet been tested in court.
Statutory Instruments: Parliamentary procedure
Generally a statutory instrument, though made by a minister and not Parliament, must go through some sort of parliamentary scrutiny process before it becomes or remains law. The exact procedure varies but however it is done there is no power to amend, and in practice it is almost unheard of for an instrument to be rejected or annulled. Between 1950 and 2015 only 17 out of over 170,000 statutory instruments were rejected by Parliament.
The last time the House of Commons exercised its power in this way was in 1979 when, probably as a result of some procedural confusion, it annulled The Paraffin (Maximum Retail Prices) Revocation Order. For reasons too technical to explain here (and which I don’t altogether follow myself) the effect was to cause the Privy Council to issue the The Paraffin (Maximum Retail Prices) Revocation (No. 2) Order which revoked the revocation. The rejoicing, if there was any, of those who objected to the removal of the cap on paraffin prices was short-lived. On the very same day the Energy Minister issued the The Paraffin (Maximum Retail Prices) Revocation (No. 3) Order, thus revoking the revocation of the revocation. Farcical is perhaps too kind a word for this sort of nonsense.
Parliamentary scrutiny of statutory instruments is in practice so minimal that it would be unfair on vestigia to call it vestigial.
(It is outside the scope of this blogpost, but one of the indirect effects of Brexit by virtue of the European Union (Withdrawal) Act 2019, has been to hand to Ministers the power to make statutory instruments on a hitherto undreamt of scale, including many powers to amend Acts of Parliament by ministerial decree, so-called “Henry VIII” clauses).
Coronavirus Regulations: Emergency Procedure
S.45Q of the 1984 Act provides that statutory instruments containing regulations under S.45C should not become law unless:
“a draft of the instrument has been laid before, and approved by a resolution of, each House of Parliament.”
In theory, if not in practice, this should ensure a higher level of scrutiny than most statutory instruments receive. That is quite sensible given that the regulations capable of being made under S. 45C have been described by a Lord Justice of Appeal as “possibly the most restrictive regime on the public life of persons and businesses ever, certainly outside times of war.”
However, since Parliament was in recess, this procedure could not be followed.
How then could Mr Hancock create the law with which Mr Corbyn has been hit? The answer lies in Section 45R which allows for an emergency procedure – an emergency within an emergency if you like – where:
“The instrument may be made without a draft having been laid and approved … if the instrument contains a declaration that the person making it is of the opinion that, by reason of urgency, it is necessary to make the order without a draft being so laid and approved.”
The regulations themselves do indeed contain such a declaration:
“In accordance with section 45R of that Act the Secretary of State is of the opinion that, by reason of urgency, it is necessary to make this instrument without a draft having been laid before, and approved by a resolution of, each House of Parliament.”
Some might question why there was such urgency to make a law targetting event organisers with a £10,000 fixed penalty on August 28th when the instrument could have been made in the usual way, laying it before Parliament at any time between March and July, when Parliament was sitting and the incidence of the disease was much higher; or why it could not wait three days until Parliament returned from its summer holiday on September 1st, but Mr Hancock’s bland statement that he thinks such urgency exists is all the law requires.
There are a few more general points.
The regulations do provide a “defence” of a sort to the organisers of political meetings. They do not apply to events organised by a “political body” if the organiser has carried out a risk assessment and taken “all reasonable measures to limit the risk of transmission of the coronavirus.” It is possible that the ad hoc alliance of lock-down sceptics of which Mr Corbyn is a supporter comes within the definition of a “political body” under the regulations, but it is very improbable, given the aims of the alliance, that it had taken any measures, let alone all reasonable measures, to limit the risk of transmission.
Payment of the fixed penalty is optional, in the sense that payment of a speeding ticket it optional. If Mr Corbyn pays the £10,000 no conviction is recorded against him.
If he chooses not to pay the fixed penalty he can be prosecuted in the magistrates court for the offence of breaching the regulation, and if convicted he would be liable to an unlimited fine. He cannot be imprisoned for the offence itself, but if he refuses to pay any fine imposed he can be imprisoned as an enforcement measure. For a fine of up to £10,000 the maximum period of imprisonment in default is 6 months. For a fine over £10,000 it is 12 months. No-one can predict what fine a Magistrates Court might impose, but there is no maximum fine. Presumably the £10,000 fixed penalty figure would be taken as some sort of guide.
The 28th August regulations fix the FPN for someone involved in an unlawful gathering at £10,000. There is no discretion given to set a lower amount.
You might assume perhaps that – as some government publicity seemed to imply – that it is only the “organisers” of such a gathering that are at risk. Your assumption would be incorrect. The S.5B (1) offence is not to “organise” but to:
“hold or be involved in the holding of a relevant gathering.”
“Involvement” is not defined except to make clear that:
“a person is not involved in the holding of a gathering if that person’s only involvement in the gathering is by attendance at the gathering.”
The implication is that without those words simply attending at a gathering would count as “involvement” in its holding. Thus, the regulations seem to catch anyone who, for example, publicises a demonstration (perhaps by posting a tweet or a link on Facebook). Even chanting slogans or carrying a banner goes beyond mere “attendance.” This means that in practice virtually anyone attending a “relevant gathering”, or encouraging others to attend, can be liable to a £10,000 FPN.
The penalties can be issued by an “authorised person,” which include a police constable or a community support officer (see Reg 9 (13) of the No. 2 Regulations, if you are still with me). Some might consider it remarkable that any police officer can now issue the organisers of political meetings with a demand for a sum of money so large that very few private individuals would have a hope of paying, and quite extraordinary that this is a power given even to Community Support Officers.
The quasi-criminal procedure of the FPN was originally devised to deal with minor parking and traffic offences. Over the years their use has expanded, to include minor public order incidents, litter, dog fouling and the like. Until the Coronavirus Regulations the maximum amount of any fixed penalty was £500 (for permitting noise from licensed premises). The procedure has now been deployed, with 2 days notice and no Parliamentary scrutiny of any sort, to target the organiser of a political meeting with a sum 20 times greater than any fixed penalty ever before created under English law. This is unprecedented and deeply disturbing and no less so because it is being used against a crank.
The fact that Mr Corbyn may be a crank, and that many of those at his meeting may have had disreputable or even disgusting political opinions is quite beside the point. As Sedley LJ put it in Redman-Bate v. DPP EWHC 733:
“Free speech includes not only the inoffensive but the irritating, the contentious, the eccentric, the heretical, the unwelcome and the provocative provided it does not tend to provoke violence. Freedom only to speak inoffensively is not worth having. … From the condemnation of Socrates to the persecution of modern writers and journalists, our world has seen too many examples of state control of unofficial ideas. A central purpose of the European Convention on Human Rights has been to set close limits to any such assumed power.”
I’m afraid Mr Corbyn will look to the European Convention on Human Rights in vain. The judges will say that the government was entitled to make the law that it did, and that even if his right to freedom of speech and assembly has been engaged, any restrictions were “necessary in a democratic society” for “the protection of health,” something specifically permitted under the Convention.
If Mr Hancock’s emergency law is upheld by the courts, as I expect it will be, so much the worse for the law. There may very occasionally be a place – in a true emergency – for significant changes to the criminal law to be made by ministerial proclamation, without warning, without debate and with no opportunity for Parliamentary scrutiny, but in a democracy those occasions should be kept to an absolute minimum. There are plenty of countries where decrees are routinely issued to prevent or deter political demonstrations. Why are we trying to emulate them?
(Since this blog was originally posted, a planned demonstration tomorrow on trans rights was cancelled, after the police warned the organisers that participants, stewards and even BSL interpreters might be arrested if it went ahead. I am grateful to the commenter Anne Coombes (below) who drew my attention to this). | <urn:uuid:2ee94ff1-1165-4cd7-86aa-89c88da539c6> | CC-MAIN-2023-40 | https://barristerblogger.com/2020/09/02/piers-corbyn-may-be-a-crank-but-his-treatment-should-worry-us-all/ | 2023-09-28T18:17:04Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.962952 | 3,391 |
A teacher I'll never forget
I was recently asked to contribute a piece to Story Time Teen, a website featuring letters from authors to their teenaged selves. I wrote about an experience that has stayed with me for over 50 years, from the time that my family made a short-lived move from our Queens home to a Baltimore suburb. The story is about my 7th grade teacher who taught me what real strength looks like. Among my most vivid memories, I think of it as a most transformational moment of my childhood. Many who read the original posting on Story Time Teen wrote to me, saying that it triggered memories from their childhoods, spurring them to re-evaluate the meaning and influence of those experiences. These readers also encouraged me to share it here, in my blog.
To access on Story Time Teen click here, or read below.
To My 13-Year-Old Self,
You moved back to Queens just in time to celebrate your 13th birthday. Living in Baltimore for four months was stressful for you, but eye-opening for me. The experience has lived in me for a lifetime, although perhaps you would have preferred to forget it.
During the summer before seventh grade, Dad invested in a restaurant in Baltimore. Until then, you had lived in Queens, NY, after moving there from the Bronx when you were a toddler. In retrospect, it seems that you just kind of existed rather than giving thought to much of anything, neither happy nor sad, just there. But being uprooted to live in a new city, you instantly felt homesick for that existence, however empty it might have been. Your older siblings, both young adults, would not be joining you.
You, Mom, and Dad moved into a newly built townhouse in a suburb of Baltimore. School began just after you settled in. On the first day, all the kids gathered in the schoolyard, waiting for the doors to open. Everyone seemed to know each other. They also knew that the chalk numbers on the asphalt indicated class assignments and that you were supposed to line up behind your class number.
A couple of the boys on your line asked if you were new. You nodded. Then, one asked where you were from. “New Yawk,” you shyly replied, which, to your confusion, was met with a few giggles. “You talk weird,” one of them said. Being noticed was bad enough but being noticed for being different was the worst possible thing. Even though you felt that they were clearly the ones with the accent, you were the one teased for speaking strangely.
You discovered you were adept at deflecting the teasing with a smile and a knack for changing the subject. What worked best, though, was being invisible, slipping under the radar. But it still hurt, so you were always on high alert to avoid the harsh glare of the spotlight. You always prayed the teacher wouldn’t call on you and, somehow, she must have sensed your trepidation, because, mercifully, she bypassed you when calling on kids in class.
Do you recall what rescued you? Basketball tryouts! As part of the gym class, all the boys in seventh grade were required to try out for the school basketball team. Had it not been mandatory, there’s no way you would have gone. After all, extracurricular activities, especially if they were unsupervised, were prime opportunities for tormentors.
Well, it turned out that one of the best things about growing up in Queens was that boys played basketball 24/7. So even the least talented among you was well-practiced. Although your skills were about average by Queens’ standards, here in the Baltimore suburbs, they were stellar. Some of the boys dribbled with two hands (unheard of in Queens!) and passes to teammates could go astray by yards. Although you were the best player in this group, you held back, not wanting to call too much attention to yourself. Who knew where that might lead?
You had no interest in being a hero. The objective was to be invisible. Once your basketball prowess was established, there was no more teasing about your accent. You didn’t feel cheerful about this. Just relieved. And you were constantly worried that something might trigger the mockery.
As for your teacher, Miss Stallnaker, I still think about her fifty years later. The crossing of your paths would turn out to be far more important to you – to us – than you could have ever known at the time.
Miss Stallnaker was sitting at her desk at the front of the room that first day as you all filed into the classroom. There were name cards on the desks, so everyone knew where to sit. Miss Stallnaker was attending to some paperwork on her desk but looked up to give each of you a warm, but reserved, smile as you headed toward your seats. She seemed nice. I still remember her smile. It felt welcoming and safe.
Once we were all seated, she rose from her desk, walked to the blackboard and wrote her name in broad strokes of white chalk. Miss Stallnaker. Just Miss Stallnaker. I still don’t know her first name; it never seemed relevant back then. She pointed to her name and said, “Hello. My name is Mith Thtallnaker.” What? She began her next sentence, seemingly rushed to get that introduction out of the way. The next sentence, whatever it was, included an “s” that came out as “th.” Miss Stallnaker had a lisp! Not just a slight slur of s’s, but a full-on substitution of every “s” with an unmistakable and clear as day “th.”
The snickering started even before she had completed her second sentence. Miss Stallnaker ignored it, pretending not to notice, and kept on going. She told the class that she had been a student-teacher and that yours was her first official class. In retrospect, she couldn’t have been more than twenty-three or twenty-four years old. The boys around you tittered, feebly attempting to muffle the sound if she looked in their direction. The gigglers would want their peers to hear their laughs, but not her. Or maybe they did, a manifestation of a dare culture seemingly universal to adolescent boys. You didn’t know what to do, paralyzed by the desire to appear as one of them and, at the same time, feeling like Miss Stallnaker and you were adrift in the same boat.
At recess, the kids were relentless in their mocking of Miss Stallnaker. You stood off to the side, close enough to be perceived as part of the group, distanced enough to avoid being noticed.
Despite it all, Miss Stallnaker almost always smiled. She had a friendly face. She was soft. Maybe that’s why she was an easy target for adolescents. She was vulnerable and didn’t seem to have a corresponding strength to offset it. The boys became emboldened, their mocking less concealed.
About three weeks into the school year, as Miss Stallnaker was standing in front of the class doing a lesson, she began to tremble. Her eyes moistened and her face reddened. She burst into tears, exclaiming, “Stop making fun of me. I can’t help how I speak.” Then she ran out of the room. You were stunned. Everyone was stunned. No one said anything. The silence was deafening. You all just sat there, not knowing what to do.
Shortly after she ran out, the principal entered the room. He was older, with a hard face and short-cropped white hair and he looked angry. You were all scared. He firmly said, “The teasing stops now. Miss Stallnaker is trying her best. There will be no more mocking her.” Then, with a final stern look for emphasis, he stormed out. He was in the class for but a minute. After he left, not a peep was uttered.
Moments later, Miss Stallnaker was back in the classroom. Her first words were “I’m sorry for what just happened.” Then, as if the entire episode had never occurred, she continued the lesson. There was no more teasing of Miss Stallnaker after that day. Not even in the schoolyard out of her earshot. She still smiled a lot, but she never looked happy.
Three months later, Mom and Dad decided it was time to move back to Queens. The restaurant did not pan out as they had hoped, Mom missed being near Grandma, and they knew you were unhappy, although you had never mentioned it. Over the Christmas break, you moved back to Queens. There were no good-byes. It was as though you had never been there, as though you had indeed been invisible.
Back then, you didn’t think your time in Baltimore would be a defining moment in your life. It’s often difficult to know which experiences will stay with us, will move us. But this one did, ever more so as time went on. A grown-up crying? A grown-up expressing what was felt on the inside? Wow. While you felt understood by Miss Stallnaker, so much of that could have been your own projections at the time – discovering a connection with someone when there were so few to be found was so comforting, even if imaginary. At least that’s what you thought back then.
I often take myself back, wondering if a Miss Stallnaker had entered your classroom back in Queens, would you have laughed along with the other boys? Would you have been sensitive to, even aware of, what made someone else feel different or unsafe if you hadn’t felt that way yourself? I like to think you would have, of course. Nevertheless, at that moment in time, you felt closer to your teacher than to your “peers,” and that feeling was eye-opening. In whatever way you were able to understand empathy at thirteen, to appreciate it, it has changed us fundamentally. That is why the experience has stayed with you.
You were lucky to move back to the safety of a town you felt part of, with people who spoke like you. Your life went back to normal in a way that allowed you to put Baltimore behind you. You had been teased just for having a regional accent and could easily chalk it up to a less than ideal time in your life. You had a skill in basketball, an understanding of a game, that paved the way for commonalities between you and your peers that leveled the playing field.
But what about those who don’t? What about the Miss Stallnakers of the world who move through life with a difference that is constantly on display, a difference they can’t escape? I tend to think that people who denigrate those who are different are either insecure or ignorant. For you, the seed of this understanding germinated at thirteen.
Miss Stallnaker just wanted to teach seventh graders. Maybe she was lonely. Maybe she was embarrassed about the lisp, something that should never matter, but regardless, she just wanted to teach seventh grade. She hoped to enlighten and educate students who were at a challenging age. She was a good teacher, too, but no one in that class let her fulfill her potential, because they were too focused on how she spoke rather than what she was trying to say. You will never forget how she came back in the room after the principal left, with a resolve to do her job and move forward after feeling belittled to her breaking point. While you wanted to hide when the going got tough, she just kept going. What a hero she has become to me.
As you moved through all the stages in your life, and eventually became a parent, it’s this lesson that you’ve held onto and have wanted to pass down to your children. Kids can be cruel as they begin to navigate new interactions, but so can adults. The world is full of people who see others with differences as being “less than.” You had the opportunity to learn that when you are treated as less than, it can be hurtful. Because your experience as an outsider was short-lived, you were able to move on from those awful feelings, and I know I’m lucky for that.
But I am forever grateful for your experience of not being accepted for who you are, because you would come to discover that knowing what it’s like not to fit in makes it easier to recognize that feeling in others. This can help you learn, grow, and develop into a more empathic person.
And that’s why, above all, this is less a letter of sage advice from your older self, but a letter of appreciation to you for going through a rough time, ultimately making it possible for me to be a better person. And, today, what I feel most strongly about your – our – experience for those few months in Baltimore is that I wish I could give Miss Stallnaker a hug. I’d want to let her know that her kind spirit and her strength have been remembered, and cherished, over a lifetime.
Your Older Self | <urn:uuid:a3bb98e0-4229-4371-a57c-2e1bcefe3535> | CC-MAIN-2023-40 | https://barryeisenbergauthor.com/blog/a-teacher-ill-never-forget | 2023-09-28T17:54:20Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.990564 | 2,791 |
This offering is for canvas prints of the “Old Galveston Square” original oil painting. Old Galveston Square canvas prints are a beautiful piece of fine art to add to your home or business.
Canvas prints are mounted on a reinforced stretcher frame with black gallery wrap edges and comes ready to hang out of the box.
Copyright watermarks will not be on your paintings or prints. Purchase of my art, originals or in print, does not convey any copyrights.
I hope you enjoy the art work as much as I did painting it. | <urn:uuid:485fee99-3b25-4ea1-affe-d24d92d081f4> | CC-MAIN-2023-40 | https://bartlettpairart.com/product/old-galveston-square-canvas-prints-of-original/ | 2023-09-28T18:33:55Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.946301 | 125 |
Basement renovation costs are always well worth it at the end of the day. This is a statement of fact that has proven true for everyone who has decided to take the step. Your home is never perfect without a finished basement that boasts its value and increases its livable space.
Basement renovation comes at different prices. This range is mostly dependent on the size of the basement and the quality of the materials you want to have in there. On average, if you are going for complete luxury, you would incur about $35 – $55 per square foot. Using the size of your basement, you can do the math and find out the size of your basement.
In this guide, we are going beyond the total/average cost of finishing your basement. We will deeper and take a look at the breakdown of the various expenses you are most likely to incur.
We will also take a cursory look at the multiple factors that can influence the total cost you will incur in the course of the renovation. Keeps reading to answer all the questions you may have about basement finishing.
Related article: Basement Renovations on a Budget
FACTORS THAT INFLUENCE THE BASEMENT RENOVATION COSTS
The cost of basement renovation for different houses and persons is dependent on a number of factors. These factors are peculiar to various persons and should be taken into critical consideration. Here are some factors that can influence your basement renovation prices.
This has been mentioned earlier as the fundamental determinant of the cost of renovation. The bigger the basement, the more the cost you will have to incur. Renovation costs can be measured per square foot. Once you get this measurement, it becomes easier to work on your budget.
This is also very critical to your budgeting. Ground conditions vary for different basements. The term ground conditions encompass the cost of excavation, the type of waterproofing you want, as well as how far your home is from the construction needs.
Excavation costs depend on the amount of debris and waste to be removed from the basement. Basements also need waterproofing, which comes in different qualities. The one you pick gives either a nudge or a dent to your budget. The distance of your home to the necessities for basement finishing projects will also influence the cost of basement finishing.
Are you thinking of turning the basement to just a workshop, or you plan to convert it to an in-house cinema? The eventual plan you have for space will affect the cost of basement renovation.
Various plans come with different needs, and materials and all these play a significant role in how much you will spend. When trying to estimate the cost of your renovating your basement, try to factor in the prices of the utilities.
COSTS ASSOCIATED WITH BASEMENT RENOVATION PROJECTS
Having your basement area renovated offers you more value than you can imagine. This is the primary reason several homeowners take the pain to restore these spaces to meet a specific need in their home.
Adapting your basement to your need comes with peculiar obligations and utilities. In this guide, we will be taking a look at the vital installations and services needed to turn your basement into a valuable, comfortable space. This breakdown includes essential utilities that ensure the livability of the basement.
You don’t want to shuttle between rooms through stairs just to get water into and out of your basement. To make the space perfect for anything you may want to morph it into, you need to get the plumbing done. With the plumbing done, water supply and sewage lines will be created. If your basement will have a bathroom area, this is non-negotiable.
Getting this done is not a job for just any random or self-made plumber. You need the help of a professional, preferably someone who has experience in fixing basement plumbing needs.
This is because this is one of the most sensitive aspects of the renovation. During plumbing, you may need to tear down parts of the wall, and you don’t want the whole house crashing down. Also, a professional means that you will be sure of the effective management of the plumbing part of basement renovation.
Building permit costs are unavoidable during a basement renovation. By renovating your basement, you are making changes to your home, in one way or the other. To avoid hefty fines, you need to get a permit before work starts in earnest. This is very important, especially since plumbing, amongst other fittings, will be done on the home. Get approval from your local government office before you get the technicians and material in.
Before you get a bathroom fitted in your basement, you need to have it inspected. This way, the blueprint of the space is verified, and the best way to get the plumbing work done is drawn out.
When the plumbing work is then done, you need to get another inspection done for electrical fittings. Doing this will ensure the whole renovation process is up to standard and wouldn’t attract legal actions by the government.
All these inspections are necessary at different stages of the renovation, to ensure that every risk of hazard is anticipated, figured out and solved. To avoid complications, the cost of inspections must be added to your basement renovation costs.
This cost comes in when the space you are working with is big. If the basement area is large and would be too much for one particular structure, sectioning is an excellent idea. This is especially good if you are looking to have a basement renovation done for more general purposes. You can section and use the various designated spaces for different purposes.
If you are looking to erect walls for these sections, you are going to have to incur the cost of the framing. The cost of basement renovation that will involve framing will be based on these elements;
- Demolishing run down existent walls
- Size of room, and the extent of framing needed
- Erection of more walls
- Soundproofing and other functionalities to be done on the wall
All these culminate into the potential cost of basement renovation, with regards to framing.
INSTALLATION OF A DRYWALL
When you finally decide to add a new walled area to your basement, you need to think of getting drywall installed too. The importance of this cannot be overemphasized, especially once the framing is done. In this case, your cost can vary depending on the type of drywall to be installed.
In most cases, drywall prices average about $10 to $20 for each panel. When this is done, follow this up with the planning and the installation. Per square foot, installation can be as high as $1.50. The cumulative cost is then dependent on the area of your basement.
Once the installation cost is taken, decide on the type of finishing to be used for the wall. Several textures can even make your drywall soundproof — getting your wall soundproof can cost you as high as $50.
Electric fittings are the next logical step when your plumbing and wall fittings are done. The cost of appliances and utilities is moderate and should be calculated during the inspection by an engineer.
Depending on how vast the area is, the electrical fittings part of basement renovation costs can be hiked as a factor of the number of hours the engineer will be working. Per hour, billing by ab engineer can be as high as $50 to $100.
Wiring is essential in the basement if you want it to serve your needs. Lighting up the basement will surely be a need and can’t be overlooked. To avoid below-quality work, meet with a licensed engineer. Your quote will depend on your house’s space and the professionalism of the engineer in question.
Related article: Cost of Basement Finishing
Basement renovation cost in Canada varies significantly by the various factors that have been discussed above. Getting your basement renovation done is very important if you need extra space. The investment is worth it, as it will lead to a correspondent surge in the value of your home.
The cost you incur is dependent on what you want to use the basement for. Whatever you decide, make sure that your basement renovation operation and costs are handled by the right set of professionals. Most importantly, make sure all the legal paperwork required for a smooth project is gotten to avoid any issue.
Are you looking to get your basement renovated? Perhaps you have lingering questions about basement renovation costs? Contact Basement Renovations Now today!
Related article: How To Hire A Basement Renovation Company in Ontario | <urn:uuid:f181aa37-0970-451f-95b2-92253e4984e0> | CC-MAIN-2023-40 | https://basementnow.ca/basement-renovation-costs/ | 2023-09-28T17:13:52Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.944475 | 1,806 |
Are the Baltics worth Visiting?
How do the Baltic capitals compare? Are the Baltics inexpensive? And the bigger question…are the Baltics worth visiting?
I cover that and more in this post.
Are the Baltics worth visiting?
A few years ago I ran into our upstairs neighbour at the mailbox. After a few niceties, she came out with a question that took me off guard: “Do you think we make too much noise?”.
I could have told her “Are you kidding me?! You guys are great neighbours!!” which is no doubt what she wanted to hear. But the truth is that they had two young, bratty kids who would spend hours riding their miniature bikes in the corridor above our ceiling while screaming at each other at the top of their lungs. In fact, the only reason we had never said anything was that the husband was my friend and I didn’t want to create friction. But here she was asking me a direct question. So I blurted out the truth “Well, it can be pretty noisy especially when your kids are riding their bikes on those wooden floors…”
She never spoke to me after that and the only time the subject came up again was about a year later when they moved out and my friend told me “Now you won’t have to worry about that noise anymore…”
So do you really want me to be honest about the Baltics?
I won’t ever say that the Baltics aren’t worth visiting because we always learn something about the places we visit. The Baltics countries have a unique history within Europe as well as distinct personalities among themselves: Lithuania has cultural and religious ties with Poland, Latvia and Estonia were both part of the Hanseatic League and have a lot of German culture, Estonia has cultural and linguistic ties with Finland. All three countries suffered horribly under both Nazi and Russian occupation.
Historically, I found that all very interesting and in each city we visited multiple history museums.
And, in support of the Baltics, I will also say that Vilnius, Riga and Tallinn are all pretty cities. There is one I liked more than the others (more on that later) but they are all pretty cities…
But if you really want me to be honest, not once during our 10-day trip did we feel “wowed” by anything. We appreciated the pretty architecture and we were interested by the history…but if you asked us what lasting impression stayed with us when we got on the plane going home I can’t say anything did.
Unfortunately that’s usually the barometer that people use when evaluating a place. We’ll never, ever forget the Bay of Kotor in Montenegro which is one of the most incredible geographical locations we’ve seen anywhere, Lviv (Ukraine) and Olomouc (Czech Republic) forever stick in our heads because of their charming old towns and beautiful churches, Guanajuato in Mexico will always be remembered because of the views from the Pipila statue and the colours of the city, and Morocco (which I had a love/hate relationship with) will always evoke emotions because of the geographical and architectural beauty. These places all leave lasting impressions and emotions for us.
That didn’t happen to us in the Baltics.
I don’t regret that we visited Lithuania, Latvia and Estonia. And like I say, I wouldn’t ever say that the Baltics aren’t worth visiting.
But if you ask me I might suggest a few other places higher on my list…
You might not agree which is fine.
Or you can blame me for being honest like my neighbour did.
Are the Baltics Inexpensive?
I’ve read posts by other bloggers saying that the Baltics are “inexpensive”, “dirt cheap” and “among the cheapest countries to visit in Europe”.
A sample of prices we found in the Baltics:
Breakfast sandwich in a café in Vilnius: 7 Euros
A pint of beer in Riga: 4.50 Euros
Average main course in a restaurant in Tallinn: 15 Euros
Average cost of a coffee in the three cities: 3 Euros
We found Vilnius to be the least expensive city and Tallinn the most expensive. But Tallinn was also the most touristy and Vilnius the least touristy so that has something to do with it.
Overall though, we didn’t find the Baltics “inexpensive” or “dirt cheap”. Prior to 2020 we travelled full-time for 6 years, spending most of it in Europe. At the time we had our finger on the pulse of what was cheap and what wasn’t. Maybe we’re out of touch now with Covid, post-pandemic inflation, and now living in Spain*. Maybe my comparisons are out of date?
*Ps. Everything is relative. If you’re coming from the UK or US, the Baltics might seem inexpensive. But coming from Spain it is definitely more expensive.
We usually didn’t like to blow a lot of money in restaurants, as I like to say “food goes in one hole, goes out another. Why spend 100 Euros/day paying for food in restaurants?”. We’d rather spend that money on a more tangible experience. So instead we usually look for the nearest supermarket and do our own shopping. And for that the Baltics were excellent: we’d buy great rye bread, pumpernickel bread, cheeses, pickles, tomatoes, pickled herring and ham for sandwiches. The grocery stores in each country were well stocked and we’d find oriental soups, good wines from around the world (in Spain we have great wines but you’ll find very few imports since it’s such a large wine producing country). In Lithuania I bought a bottle of Starka at Iki Express (a local supermarket). Fantastic. In Latvia I couldn’t find Starka at Rimi Express (a great supermarket in Riga’s old town) but to my surprise, did find a bottle of Ararat brandy from Armenia (I was addicted to Ararat when we spent a month there a few years back). Guess what? I taste-tested the two and actually preferred the Starka.
In short: save money by buying your food at the supermarkets instead of going to restaurants. Everything was of excellent quality in all 3 cities.
I should add to the above: We paid 16 Euros/pp to take Flixbus between Vilnius – Riga (a 4 hr drive) and 12 Euros/pp Flixbus Riga – Tallinn (a 4 ½ hr drive). I think that IS inexpensive.
Are the Baltics “less discovered”?
I had a few people mention to me (when I announced our plan to go to the Baltics) that it’ll be interesting reading about a place less discovered.
In actual fact, there were lots of tourists when we visited in late June. Tallinn was especially full of tourists, including Asian tour groups. When you see Asian tour groups you know a place is not less discovered.
Riga had lots of younger tourists, Vilnius seemingly less tourists (although they might just have blended in more because of the layout of the city).
Just know that the Baltics aren’t undiscovered.
Weather and the Sun
There was one major reason we were visiting the Baltics in the summer (we were there late June): we wanted to get away from the heat of Spain. We didn’t really achieve that: temperatures were in the low 30’s almost all of our 10 days.
But we did encounter one thing we hadn’t expected: because of its high latitude, the Baltics get a lot of sunlight hours in the summer. We thought it weird when we arrived in Vilnius and the sun was setting at 10:30 PM…well, the days got even longer as we went further north first to Riga and Tallinn. As a tourist it means lots of daytime hours to walk around sightseeing. But it also screws you up a bit, especially when the sun comes back up at 4:30 AM! After a few days you might find yourself walking around like Al Pacino in “Insomnia”…
Note: in the winter it’s the opposite, the Baltic countries getting very few daylight hours (in December the sun comes up around 9 am and sets around 4 pm).
Comparing the Three Capitals
1. Vilnius was our favorite of the three cities. It’s city full of churches, pretty squares, and green spaces. What we liked above all is that the old town meshes with more modern part of town (unlike either Tallinn or Riga which both have very distinctive old towns) which means you’ll see locals walking around doing their business. A very liveable city with a coffee culture and some beautiful architecture.
Much more detail here: What to See and Do in Vilnius (and what to skip)
2. Tallinn has the prettiest old town of the three…but it is very touristy and in some spots a bit Disney-ish. Everywhere you look you’ll see medieval walls (it has one of the most intact old towns in Europe) and Hanseatic architecture. In the upper town there are lots of views looking down on the lower town and the Baltic Sea. Of the three countries Estonia is the richest, benefiting from its technology sector and trade with Finland. Outside the old town you’ll see sparkling high rises.
3. Riga comes last on the list. It is a pretty city but the old town is very touristy and appeals to a younger demographic. You’ll see lots of bars and hostels. It feels like there are few locals in the Old town, maybe owing to the canal that divides it from the rest of the city. Our highlights were actually outside the old town, seeing the Art Nouveau architecture on Alberta iela and the Russian Orthodox Church.
Have you been to the Baltic Countries? Have an opinion?
Related: Our worst ever Train experiences | <urn:uuid:b0cfbc74-df0d-43da-9e4b-87eb83aa29fc> | CC-MAIN-2023-40 | https://bbqboy.net/are-the-baltics-worth-visiting-and-ranking-the-baltic-capitals/ | 2023-09-28T16:57:34Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.969463 | 2,164 |
The Treaty on the nonproliferation Treaty (NPT) came into force 03 05, 1970, with the is designed of ensuring that firstly, the five known nuclear declares (the USA, China, England, the Societ Union plus the United Kingdom) did not offer or give nuclear weapons to nonnuclear states., The second pillar requires signatories to deliberately solidify international trust and alleviate tensions between states. Third, the treaty discourages nonnuclear states from developing elemental weapons yet allows these to import and develop neclear technology to get civilian reasons.
Since 1970, other states have got joined the nuclear positions, whether openly or secretly. These include India, Pakistan, North Korea, His home country of israel and Usa. The U. S. foreign nuclear non-proliferation policy towards Iran is unsucssesful badly. The principal reason for the failure is definitely President Bush’s choice of taking on a confrontational stance against Iran. One of the reasons why Serbia has attacked its elemental campaigns often is the anxiety about an harm by the U. S., whose forces inhabit Iraq and Afghanistan.
The U. H. could attack Iran straight or through Israel. Iranian nuclear growth is consequently motivated into a large extent by need to prevent external hostility. Tehran will invest even more in its elemental programme so long as there were indications of an upcoming attack in the USA or perhaps her sympathizers. The second reason for the failure of the US non-proliferation coverage is the picky nature with the policy. The selective way is seen in USA and other NPT signatories’ pre-occupation with all the Iran and North Korea, while stating nothing about India’s, Pakistan’s and Israel’s nuclear programmes.
Iran’s elemental programme is usually roughly since old as they new indivisible states the U. T. has served as if just Iran and North Korea had nuclear ambitions. Predictably, both Iran and North Korea ignored U. S i9000. selective pressure and ongoing their indivisible programmes. Coverage Recommendations towards the problem America and other strong states need to pursue a non-discriminative approach to nclear nonproliferation. The US manages to lose all ethical authority to direct Iran, North Korea or Libya to destroy their nuclear projects when doing and saying practically nothing against Israel’s. If any international counter-proliferation laws should be bear fruit, chances are they must be accompanied by all claims.
The result of the selective procedure is that Iran has won some support from China, Turkey and India, making it hard for the USA to take disciplinary measures against Iran. Lack of China’s approval for another rounded of calamite on Usa, or a conceivable military assault, to damage Iran’s elemental facilities shows that even the identified nuclear declares are divided on the issue, a state of affairs which makes it difficult to arrive at a decision. The second recommendation is that the US must drop it is confrontational posture against Usa.
Iran, which seeks to become the local supremo in the centre East, responds with aggresiveness and bravado to ALL OF US threats of sanctions and attacks. In case of an harm, Tehran is most probably to hit back again with its indivisible weapons, ultimately causing a elemental confrontation. America, despite the superpower status, must drop its dictatorial mentality and seek instead to explore economic and diplomatic options.
Similar to most other full sovereign coin states, Serbia will are at odds of nuclear nonproliferation policies which usually discount their security worries or present no esteem for its sovereignty. Pursuing a nonproliferation answer in a diplomatic or detrimental manner, with no use of name-calling, falsehoods and dis-information, threats and unlimited series of financial sanctions against Tehran, improves opportunities of a productive indivisible non-proliferation discussion between Iran and the ALL OF US. | <urn:uuid:a147cf63-00f5-4e1f-b7c6-e179f68df3f7> | CC-MAIN-2023-40 | https://bclforge.com/u-s-nuclear-non-proliferation-policy-towards-iran/ | 2023-09-28T18:50:07Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.941115 | 799 |
About Beachwood Dental
Comfort, quality, & care
As one of the leading dentists in Beachwood, Dr. Paul Mikhli, founder of Beachwood Dental, has a wealth of experience in oral hygiene. And our team of skilled Beachwood dentists knows the ins and outs of how important oral health is, no matter the age. We provide the highest quality dental care for our patients daily. We accept most insurance plans, and provide appropriate recommendations and procedures when needed.
Located in Beachwood and serving the greater Cleveland area, Beachwood Dental is a leading provider of dental services. With state-of-the-art technologies, our facility is the ideal fit for your dental procedure needs, whether you’re looking for a semi-annual cleaning, or are in need of a cosmetic dental procedure. From dental veneers to inlays and onlays, our friendly and caring staff strives to meets patients’ needs, and find the solutions that work best for them.
Our Mission Statement
We are: Dedicated to providing the highest quality of care with a commitment to uncompromised professional and individualized service to each patient.
Dr. Mikhli and staff are dedicated to providing you with a pleasant visit and results that you’re proud to show off. Our administrative staff is ready to help you with questions about scheduling, financial policy and insurance, to make that part of the process as simple as possible.
What Our Patients Say
“This is a clean environment and a very happy and helpful staff. I had extensive work done and am very pleased with how things are turning out. Dr. Mikhli is a fine dental artist.” – Kathleen S
Ready to Improve Your Smile?
Call us with any questions or to make an appointment. | <urn:uuid:c9e9bae1-f223-463d-8c01-eba9a6364a37> | CC-MAIN-2023-40 | https://beachwooddental.com/about-us/ | 2023-09-28T18:38:56Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.936851 | 372 |
The art of A K Nicholas is an unapologetic celebration of the female nude. It invites the viewer to explore a dreamlike world full of beauty and passion. The camera is merely a starting point on this visual journey to unknown destinations. His fantasy compositions draw upon disparate influences from French modernism nude paintings to more contemporary pinup art, mixed with elements of theatricality and performance. This unorthodox aesthetic blends sensual imagery with a painterly style of manipulated colours.
A K Nicholas’ view of beauty is not overshadowed by eroticism nor is it obligated to modesty, so it’s not for the timid. By design, these images appeal to select collectors; viewers who engage emotionally and intellectually, seeking inspiration rather than being told what to think.
Exclusive interview with A K Nicholas
What made you decide to focus solely on the female form?
When I was learning photography, I photographed females, males, myself, places, objects and a few landscapes. I also painted as much as I worked with a camera. When I was a sophomore, I was approached by a gallery who wanted to show my work, but they wouldn’t show anything but my images of women. Accustomed to placating the praise of the college environment, I was offended. After graduating, images of the female form continued to be the only thing that sold; it took two or three years before reality sunk in.
On your website it says “The camera is no more than a starting point on this journey toward undetermined destinations”, does this mean you go into a photo shoot not knowing what you want the outcome to be? Or do you a have a faint idea that grows and morphs into something new?
I have more than a faint idea. I know who the subject will be and where it will take place. That stacks the deck in my favour. From there, I want to explore. I like the subject to be genuinely curious about where we are and how she is positioning her body. For many photographers, the outcome is a documentary each time they click the shutter. I’d be proud if I could make compelling images straight out of the camera that way. To me, a photo shoot is when I gather raw materials. It may be years before I have enough to finish a particular piece.
Some of my compositions are obvious montages. But I approach every piece the same way as I would a painting: What color do I want her hair to be? Which direction do I want the right hand to be pointing? If I don’t have the right components, I look for them in previous shoots or wait until some future shoot.
When I look at other people’s work, say a painting in a gallery, it can be obvious that some awkward detail is there just by chance. They took a photo, it was okay but not great, and copied it into paint, flaws and all. I think we need to do more, even as photographers, not to settle for less than we can produce.
How did you create this alternate reality that your artworks depict and live in? Was it always a desire you wanted for your work or has it evolved into what it is today spontaneously?
The best answer is, “I don’t know.” My first daydreams that I turned into art were crude schematic drawings of rocket ships. I did this probably from the age of five to eleven. I would try to draw science fiction inventions in the vein of Leonardo da Vinci. But other than that, I hated art when I was a kid because my mother would make the family spend hours or days in museums while on vacation.
That changed with a surrealism art history class in high school.
“Engaging the viewer emotionally or intellectually, art should inspire our thoughts, rather than tell us what to think” What thoughts do you wish to inspire in the viewer?
None. I don’t anticipate what the viewer will think; on occasions where I tried to, the artwork ended up being a disaster. I can’t illustrate concrete ideas. The images are explorations. I don’t know what the destination is; that is determined by each viewer.
Why did you choose photography as your medium when you had been formally trained in painting and drawing?
As I touched on earlier, it occurred to me that I don’t do those things very well. I’m technically competent at getting oil paint to stick to canvas, and I still paint and draw using my photos as a reference. But it’s just a mental exercise to analyze my composition. The resulting product falls short of my standards. I’d say I’m satisfied with about 10 percent of my photography and a percent of my paintings and drawings as something I would put on my own walls. So I stick to what I can do.
Would you consider your art education as a crucial part of where your art practice is today? Or do you think that you could have achieved the same things without the formal education?
I have no basis to know for sure, but I’ll make a wild guess. If I hadn’t grown up with a parent who was an artist and if I didn’t have an art degree, I wouldn’t be the same person. I’m passionate about making art. That drove me to get a formal education, not the other way around. Many things added up over my whole life, not just building technical skills and a work ethic, but also a vision that I suppose led me to be passionate about making art.
I can’t stop making art. It’s not a choice for me.
What projects are you working on currently? What can we look forward to from you in the future?
I’m printing a series of photo books that should be available by the end of the year. For example, I am working on a square format photo book, which, in addition to digital images, includes a Hasselblad black and white film shot and maybe a Polaroid if I can achieve the one I want.
Next year, I’ll be traveling for shoots, mostly in the United States. I have been compiling a list of places I want to shoot. Some are scenic, like in the desert Southwest; others are abandoned places or other curiosities that are visually interesting in unintended ways. | <urn:uuid:8ec168e2-0874-4c75-9a49-0556b308a7e0> | CC-MAIN-2023-40 | https://beautifulbizarre.net/2020/02/14/interview-with-a-k-nicholas/ | 2023-09-28T18:16:25Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.967355 | 1,322 |
A facial can leave your skin feeling refreshed, glowing, and revitalized. It can also be a relaxing and rejuvenating experience for the mind and body. We have a number of facials to choose from, including our 30 minute Mini Facial to our 90 minute Abundant Harvest.
60 minutes of an organic and uplifting facial. Healing tones set your mind at ease while your esthetician curates a custom facial using our signature skincare which have an exceptional line high potency blends using all natural ingredients helps lift, nourish and promote healthy hydration. A sophisticated, nonaggressive facial that focuses on the brilliant unison of the latest technologies all found in Laurels skin science. Finished with hand and arm massage and aromatherapy for maximum relaxation.
Using all well trusted comfort zone line this facial offers the perfect blend of pampering and moisturizing to keep your skin revitalized. Suitable for all skin types and environmental sensitive especially! This facial will leave your skin supple, hydrated, and well rested. Enjoy facial massage for maximum lymph movement in the face and rest easy knowing this facial will also be custom to your skins current needs based on the skin in the moment.
Take the first step towards clear skin and ultimate relief of breakouts & acne prone skin with a blend of professional products and techniques in the treatment room + expert skin care education and guidance towards a daily ritual to maintain results at home. This facial treatment is customized primarily for those who struggle with acne symptoms, but is also a valuable service for those who wish to gain a better understanding of proper skin care and how to achieve and maintain healthy, glowing skin. Includes a deep cleanse, exfoliation, a mask to suit your individual needs, a boost of hydration, and extractions if necessary.
A shortened version of our custom BATL Escape facial designed for those on-the-go. This refreshing treatment cleanses, tones, lightly exfoliates, and deeply moisturizes for instantly glowing skin. Perfect for when you are in need of a quick rejuvenation, but are pressed for time.
*Extractions, Microdermabrasion, Dermaplaning, and LED Light Therapy not included, but can be added on for additional cost and time to the service. See A La Carte menu below for details.
The Bacial (a.k.a. back facial) is the best way to thoroughly remove dead skin cells and impurities for a clear back. Much like the face, excess oil, dirt, environmental pollution and bacteria become trapped in your back’s pores, resulting in whiteheads, blackheads or cysts. And similar to a facial, a bacial is designed to clarify and soften with a deeply cleansing, exfoliating and moisturizing treatment with a custom mask followed by a relaxing massage that will leave you with a healthy, glowing back all summer long.
Feel the glow with this exfoliating treatment that reveals silky smooth, revitalized skin with immediate results and no down time. It simply involves the use of a sterile surgical blade, known as a dermatome, that gently scrapes away the top layer of problem skin. Suitable for all skin types in need of a deep exfoliation that instantly sheds dead skin & debris, removes scar tissue, and peach fuzz.
LED light therapy is a painless, relaxing, non-invasive skincare treatment that has multiple benefits; particularly stimulating collagen and treating mild to moderate acne. LED treatments work by using an array of bright light-emitting diodes (originally developed by NASA) that send low-level light energy into the deeper layers of the skin to stimulate cellular activity.
Precise diamond tip technology designed to efficiently remove dead skin cells & dry, damaged skin while purifying congested pores with a powerful, yet gentle suction mechanism. This noninvasive procedure treats the face, around the lip and eye area, and body.
Book solo with a cleanse and moisturizing treatment included or add on to any facial or bacial (back facial) treatment for a deep exfoliation and boost of product absorption.
Add to any skin care treatment to condition facial hair while moisturizing the skin underneath. Designed to absorb easily into the follicles for healthy and well-manicured, designer stubble.
An extra 10 minutes for deep relaxation, stress relief, and aromatherapy. | <urn:uuid:26cfcd82-0925-4825-ab58-6310141171de> | CC-MAIN-2023-40 | https://beautyatthelake.com/facials/ | 2023-09-28T18:54:53Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.918518 | 897 |
CWITEC has released TX16Wx Software Sampler 3, a major update to one of the best freeware cross-platform virtual sampler instruments in VST and AU plugin formats for digital audio workstations on PC and Mac.
Same as before, two differently priced versions of the software are available. The basic version of TX16Wx Software Sampler 3 is freeware, whereas the more advanced TX16Wx Professional 3 comes with a €99 price tag. If you plan to use the Pro version non-commercially, the price is reduced to €39 (this version of the software is called TX16Wx 3 Pro Non-commercial). The non-commercial license can be granted even to individuals or businesses who are using TX16Wx commercially, given that their gross revenue does not exceed €10,000 per year.See also: Best FREE Sampler VST Plugins!
The latest version of TX16Wx Software Sampler 3 introduces numerous new features. The most notable improvement is the new asynchronous disk streaming engine which enables disk streaming with ultra-low latency. This will effectively optimize the sampler’s performance and reduce the amount of RAM required for smooth sample playback of large libraries. Speaking of performance, the CPU hit has been reduced as well, with improved sample interpolation and parameter processing. Other notable changes include a new program-centric user interface, better transient detection, more intuitive mapping editor, and support for VST3 and AAX plugin formats.
The Pro version TX16Wx 3 comes with its own set of improvements, in addition to those mentioned above. It now features two new playback modes – the pitch shift engine and the time stretch engine. A brand new reverb module is included, along with the improved versions of the previously available effects. The Pro version of the software now also features a MIDI arpeggiator with multiple automated patterns.
TX16Wx Software Sampler 3 remains the best freeware cross-platform sampler on the market. Grace is another excellent freeware sampler instrument, but it only works on Windows. For Linux users, Linux Sampler is still the way to go.
The software can be downloaded completely free of charge from the developer’s website. To enable the Pro version features, install the freeware version and unlock them from the settings menu. This will start the evaluation period for TX16Wx Professional 3. The instrument is compatible with all VST, VST3, AU, and AAX plugin host applications on PC and Mac
TX16Wx Software Sampler 3 is available for free download via CWITEC (29 MB download size, EXE installer, 32-bit & 64-bit VST/VST3/AU/AAX plugin format for Windows & macOS). | <urn:uuid:1d95e448-e73e-4385-a09a-9f89c486be02> | CC-MAIN-2023-40 | https://bedroomproducersblog.com/2018/10/23/tx16wx-software-sampler-3/ | 2023-09-28T18:11:18Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.888732 | 572 |
Celebrate Spring with Beksan Designs
What is it about Spring that makes us feel the way we do? Is it the sign of new life—budding leaves on trees, blooming flowers or is it a bright sunny day after a long winter? Maybe these signs of new beginnings give us a sense of hope and rebirth. Whatever it is, I see more people smiling, laughing, and wanting to create their own Spring style. It’s almost April and time to put away the sweaters, bring out the colors and lighter fabrics and make a statement!
At Beksan Designs, we’re excited about Spring too, as now we can share our new Spring collection with you. The colorful semi-precious stones in our Antika collection just scream Spring and Summer. Set in 24 karat vermeil, they are a perfect complement to your Spring wardrobe and lightweight too. Whether a necklace, earrings, bracelet, or ring, each piece is distinctive and will put a “spring” in your step.
Our scarf collection is simply gorgeous. Made from the highest quality Turkish cotton, silk, or pashmina you will take great pleasure in the look and FEEL of them, whether you use them as a scarf or spring/summer wrap. Intricately designed, each colorful scarf is a fun way to celebrate Spring!
We also have some colorful new purses in our Spring collection. The smaller, cross-body Kilim purses are perfect everyday wear. The intricately designed larger Turkish fabric handbags are a “must have” for this season. Whether used as a purse or a tote, these quality handbags are both fashionable and functional. The vibrant colors and patterns will brighten any new Spring outfit.
We’re excited to bring you new products in addition to our other collections as we “Spring” into a new season! | <urn:uuid:7c5b677d-2d3e-42b5-8a6b-1f32ec3fd032> | CC-MAIN-2023-40 | https://beksandesigns.com/blogs/beksan-designs/celebrate-spring-with-beksan-designs | 2023-09-28T18:10:24Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.925022 | 391 |
Duaa Tahir is a writer, horticulturist, and gardener. As an author, Duaa's goal is to share her knowledge and passion with others, helping beginner gardeners get started and guiding them on their journey to becoming successful and confident gardeners. When she is not busy writing or working on her latest gardening project, Duaa can be found watering her houseplants, experimenting with DIY balcony and urban gardening creations, or cooking in the kitchen with ingredients she has grown in her own garden. With her passion for nature and her wealth of knowledge and experience, Duaa is a valuable resource for anyone looking to deepen their connection with the world of gardening.
Having a beautiful lawn is all good, but the real problem comes when you have to clean it up now and then. Trust me, cleaning all the dead leaves and debris is not a piece of cake, but with the… Read More »7 Best-Selling Walk-Behind Leaf Blowers
Sometimes we forget how to properly clean and store our rusty garden tools after a long season of garden work and chores. As a result, they get all rusted up and can’t be used as easily as they should. The… Read More »How to Clean Rusty Garden Tools | 5-Step Effective Guide
Are you tired of watching your beautiful garden wither away, helpless against the onslaught of fungal diseases and pests? Struggling to decide between Copper Fungicide and Neem Oil, you might feel like you’re stuck in a never-ending battle to protect… Read More »Copper Fungicide Vs. Neem Oil – Which Is The Better Option?
The age of modern technology has brought about an explosion in useful tools and machines to make our everyday work easier and less strenuous. In the realm of gardening and outdoor work, there is an especially expansive market filled with… Read More »The Best Small Garden Tiller (Mini Tiller / Rototiller) in 2023
The market is flooded with best weed removal tool, but how do you choose what’s best? I have compiled a list of 7 products that will make your life easier.
This post will guide you through the best choices for you to consider when purchasing a garden hose reel.
I reviewed 7 of the best manual lawn edgers that I have used. Here you’ll also find a buying guide to help you make a better decision.
Do you want your garden to remain neat and clean? Are you tired of those stubborn dirt mounds that have destroyed the look of your lawn? In either case, you don’t have to worry at all. In today’s article, I… Read More »Unearthing the Culprit: How to Identify and Eradicate Dirt Mounds in Your Lawn?
My comprehensive list of the Best Small Zero Turn Mowers can help you choose the right mower for your needs. I have also put together a comprehensive buying guide to help you figure out which mower is best for you. | <urn:uuid:7472d710-1df5-4e47-a9b9-1eab7225e0ec> | CC-MAIN-2023-40 | https://belogarden.com/author/duaatahir/page/5/ | 2023-09-28T16:58:29Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.935357 | 632 |
Emergency Plumbing Tips | Plumber in Fort Worth
When you have an emergency with your plumbing fast action is required to prevent damage to your home, The following emergency plumbing tips provides instructions on how to stop the danger of the plumbing emergency before you call your plumber in Fort Worth.
- Shut the Water Off – Knowing how to turn off the water is the first most important instruction in any plumbing emergency involving water. When a fixture such as a toilet or sink is involved, turn off the cut off valve beneath the fixture. Otherwise, know how to cut the water off at the water main valve, or the water meter.
- Flooding Toilet – If the toilet has a cutoff valve shut it off. Otherwise shut the water off at the water main valve or the water meter. If you have someone to help you and must run to the basement or water meter to cut the water off, one person can lift the float valve, which stops the flow of water into the tank, while the other person shuts the water off. Once the water is off, contact a Benjamin Franklin plumber in Fort Worth for repair of your toilet.
- Turning Off an Appliance – Overflowing or leaking appliances must be handled differently depending on its location and access to a cut off valve. Unless a cut off valve is handy it may be easier to cut the water off at the water main valve or the water meter. When a washer overflows shut it off. This should stop the water. If the leak is a washing machine water supply hose, close the valve the hose attaches to. When cut off valves malfunction shut the water off at the water main valve or the water meter. It may be more difficult to access a cut off valve to a dishwasher. It may be located in a cabinet beside it or behind another appliance such as a refrigerator. When the water supply line to the icemaker busts it may be a difficult task to move a heavy refrigerator if the cut off valve is located behind the appliance. Use the water main valve or water meter cut off if this will be faster.
- The basement or other rooms flooded with standing water can pose a risk of electrical shock. Water conducts electricity, and if water contacts a bare electrical wire (which may not be visible if in a wall), dangerous or even fatal shock may occur. Do not enter a flooded room. If you can access the home’s main electrical panel without entering any water or a wet area, cut off the electric main switch. Otherwise, leave shutting the power down to a licensed and trained professional such as your plumber in Fort Worth. Some homes have two electrical supplies, one inside the home, and one outside of the home typically beneath the power meter. it also has a main switch that will shut off portions of the home’s service. The outside box will NOT shut off all power and serves only a few select appliances or services in numerous houses. If you’re in doubt, wait until a professional plumber in Fort Worth arrives to provide the repair.
- Gas Leaks – Don’t attempt to shut off or repair a gas leak yourself. Get everyone out of the house immediately, call 911 from a safe distance away from the home and the odor of gas, and then call your gas provider. When the gas is off and no longer a danger, you may then call a licensed gas certified plumber in Fort Worthto provide repair of the gas leak.
- Hot Water Leaks – If you have a hot water leak in a pipe or the water heater, turn off the main water supply and then turn off the hot water heater’s energy source. There should be an emergency shutoff valve on the gas hot water heater. Shut off the electricity supplying an electric hot water heater in the homes electric main. Then call your plumber in Fort Worthfor repair.
- Yard Line Leaks and Interior Piping – Shut off the water at the water meter and call your plumber.
- Water Meter Leaks – Water leaking on the street side is the responsibility of your water utility provider. Water leaks on your property side of the water meter are your responsibility. Shut the water off of the meter and call your plumber in Fort Worth for repair of leaks on your side involving your home’s plumbing, and the water utility department for leaks on the street side.
A Benjamin Franklin plumber in Fort Worth, can take care of your plumbing repairs, installation and maintenance with the expertise of a true plumbing professional. We always respect you, your property and strive for your satisfaction as our 100% satisfaction guarantee shows. The integrity we require of our plumbers ensures that you will receive professional and honest service. We value your business and appreciated your patronage. We provide plumbing service to Fort Worth, Arlington and the surrounding areas. We hope you found these emergency plumbing tips helpful. Thanks for visiting Benjamin Franklin Plumbing. | <urn:uuid:74e08da6-4d68-4095-8631-77dd7b6a904d> | CC-MAIN-2023-40 | https://benjaminfranklinplumbingfortworth.com/plumbing-blog/emergency-plumbing-tips-fort-worth/ | 2023-09-28T19:03:01Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.915075 | 997 |
Water Heater Replacement | Water Heater Repair Fort Worth
Like any appliance, water heaters will eventually break down. No one enjoys taking a cold shower, and the ideal situation is when a failing water heater provides signs in advance of a big leak. If you are lucky enough for this to occur, it provides a warning that it may be time for water heater replacement before worse problems can develop, such as a large leak and water damage to your home. So how do you know if you need replacement or water heater repair in Fort Worth? Here are a few clues to be aware of.
Signs to Replace: Age
As a hot water heater ages the potential for a breakdown increases. The chemistry of your water supply and the amount of maintenance provided on the water heater will play a role in the appliance’s longevity. Hard water, a lack of maintenance and ignoring the need for hot water heater repair in Fort Worth will significantly shorten its service life and reduce efficiency.
Signs to Replace: Rust and Corrosion
Inspect the hot water routinely for the presence of rust and corrosion. Furthermore, if the water appears rusty or discolored it can mean there is rust inside the tank. While there may be other causes of rust colored water, such as corroded galvanized pipe, rust can indicate the tank has failed and water heater repair in Fort Worth will not help the appliance. Leaks inevitably follow rust and the water heater will need to be replaced.
Signs to Replace: Leaking Hot Water Heater
While a leak can possibly be caused by a leaking component that may be repairable, leaks may also indicate an internal problem and a high probability that the water heater will require replacement. If your water heater is leaking, even a small amount of water can damage floors, subfloors and walls. A small leak has the potential to turn into a catastrophic flood leading to significant and costly damage to the home, and health threatening mold and mildew.
If you have recently flushed sediment from the tank and water is leaking from the drain valve, try tightening it. If the leak continues, call Benjamin Franklin Plumbing to provide water heater repair in Fort Worth.
Once you have ensured the source of the leak is the hot water heater turn off the power supply, then turn off the water supply and contact a Benjamin Franklin plumber.
The Decision to Repair or Replace
A professional plumber is the best source for identifying the cause of a leak, and the determination of whether to provide water heater repair in Fort Worth or to replace the appliance. On the positive side of hot water heater replacement, today’s water heater will be more energy efficient than an aging one, saving your household money on the cost of hot water production.
If saving energy is a key factor in the selection of a hot water heater for your home, consider tankless water heaters. A tankless water heater eliminates the loss of energy by producing hot water when it is needed, rather than reheating water in a tank repeatedly until it is used as in a conventional water heater.
Under normal conditions and with proper maintenance a tankless water heater can last significantly longer than a conventional water heater. A Benjamin Franklin plumber will be able to assist you in deciding if a tankless water heater is an option for your home.
Benjamin Franklin Plumbing offers licensed professional plumbers for your plumbing needs. Our experienced plumbers provide service with expertise for reliable plumbing you can count upon. Whether you need water heater repair in Fort Worth, water heater replacement, or other plumbing services, call the plumbers ranked as among the best in the nation, Benjamin Franklin Plumbing. We are a member of the BBB with an A+ rating, backed by our 100% satisfaction guarantee on all plumbing repairs. | <urn:uuid:60854544-4a1c-482e-9de3-0dddad0710c5> | CC-MAIN-2023-40 | https://benjaminfranklinplumbingfortworth.com/plumbing-blog/signs-to-repair-or-replace-a-water-heater-fort-worth/ | 2023-09-28T17:44:45Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.927307 | 768 |
Photo By Ratsanai at istock
Water conservation is an issue of greater and greater importance. Water is absolutely essential. It is necessary for irrigation, personal hydration, sanitation, and industrial use. Less than one percent of the water present on the earth’s surface is drinkable. This drinkable freshwater is found in lakes, rivers, reservoirs, and aquifers. Approximately one-third of the world’s human population struggles with water shortages. The average American uses more than double the amount of water each day than most Danish, Austrian, or French citizens. Plumbers can speak into this even more.
In a natural setting with little human activity, 10% of precipitation becomes runoff, 50% is absorbed into the earth, and 40% evaporates. In an urban setting, such as Arlington, TX, 55% of all precipitation becomes run-off and only 15% is absorbed. This is bad news for reservoirs and aquifers and makes water conservation even more important.
Remodeling or renovations in your kitchen and bathroom are a good opportunity to improve water efficiency. A plumber can help you choose water-efficient appliances and fixtures that work with your overall renovation goals. There are also plenty of ways to improve efficiency even without large-scale remodeling projects.
Regular Plumbing Maintenance
Maintaining the plumbing in your home or business is one of the best ways to conserve water. Poorly maintained plumbing infrastructure wastes energy and water. Consult your local plumber to keep up on regular repairs and locate small problems before they become big problems. Leaks may not seem like a big deal in the bigger picture of water conservation, but small leaks add up to a lot of water.
One drip per second becomes nearly 5 gallons each day. That becomes almost two thousand gallons of wasted water by the end of the year. EPA statistics suggest that up to 10% of all American homes contain leaks responsible for at least 90 gallons of wasted water each day. Call a plumber as soon as you notice a leak.
Faucet leaks can also be caused by worn-down cartridges inside the faucet. A plumber can fix this fairly quickly. This may seem like an easy fix, but mistakes can lead to much costlier plumbing repairs. Excessively high water pressure is also a common culprit for leaks. Pressure can stop water from flowing in a certain direction, which causes backups and leaks in other faucets or pipe fixtures.
Other common causes of leaks include cracked or broken fittings, worn-out inlet or outlet seals and washers, or problems with o rings.
One of the biggest indicators of a hidden leak is a surprise increase on the water bill. If you can’t figure out where a leak is coming from, the problem may be a series of minor leaks throughout your plumbing, especially if you live in an older home or the plumbing hasn’t been inspected for a while. Older pipes installed before 1970 could be made of iron, lead, steel, or old, brittle plastics.
A damaged water line can lose water even faster than leaky pipes. Other problems, such as low water pressure or contaminated water, may occur as well. Call a plumber if you suspect a damaged water line. It is not a good idea to fix it yourself because you could end up with even more problems and potentially extensive water damage.
Water-Efficient Fixtures and Appliances
Plumbers play a key role in water conservation on a commercial and residential level. Water-efficient plumbing fixtures are an important part of residential water conservation. Replacing old toilet models with water-efficient models can save up to 360 billion gallons of water each year in the United States.
An ‘old’ toilet in this sense is defined as a model constructed before the Energy Policy Act in 1994. Older toilets use from 3 to 6 gallons for each flush, while low flow models use approximately 1.28 gallons during each flush. Many consumers are concerned about the performance of water-efficient toilets, but most models have received satisfactory consumer satisfaction ratings in terms of flushing and cleanliness.
An energy policy act in 1992 required ll new homes and renovations to install low-flow toilet systems. This act went into effect in 1994, but plenty of older toilets are still in place in homes across America. Dual-flush toilets, which are already very common in Europe and Australia, have a lower flush option for liquid waste and a higher flush option for solid waste. Your plumber can tell you available low-flow toilets and help you choose an appropriate model.
The U.S. Environmental Protection Agency, or EPA, finds that household faucets are responsible for approximately 15% of indoor residential water use. Water-efficient faucets installed by a professional plumber can reduce water use by up to 20% and save up to 700 gallons of water each year.
Your plumber may be able to modify an existing faucet with an aerator to improve water efficiency as well. An aerator is a small device attached to the bottom of the faucet. It contains a screen that covers the end of the faucet and adds air to the water stream by disrupting the flow and breaking the water apart. This technique saves a lot of water, but the flow is still sufficient for washing and most other purposes. High-efficiency aerators can reduce water flow by approximately 1.5 gallons per minute, and the EPA categorizes aerators as one of the easiest and most effective ways to reduce wasted water.
Install a water-efficient showerhead for greatly reduced water usage in your household. Showerheads account for another 17% of the water used in most homes. Replacing an old showerhead with a water-efficient fixture can reduce water use and save money. Consult a plumber to install a shower valve sized to fit the corresponding showerhead.
The EPA estimates that the average family could reduce water usage by up to 2,900 gallons of water per year. The average showerhead has a flow rate of 2.5 gallons per minute, while a low flow showerhead has a flow rate of 1.5 gallons per minute. A good low-flow showerhead offers very similar pressure and comfort levels, it simply uses less water. Reducing water pressure is another easy way to conserve water during showers, and rinsing your shower head in vinegar can remove potential hard water deposits and let water flow efficiently with less pressure.
Water Usage Habits
Changing household habits can also conserve water in your Arlington, TX home. Pay attention to running water when your washing dishes or preparing food. Fill a pot with water to clean vegetables or other foods instead of washing them under a running faucet. Try using a basin of soapy water and a basin of clear water while cleaning up dishes. This uses much less water than letting the faucet run and rinsing dishes continuously. Soapy water can’t be used to water plants, but the water used to wash products can be reused to water plants or a garden.
You may not think of soaking pots and pans as water-saving techniques, but you may use more water than you realize attempting to remove baked-on food. Let soiled pots and pans soak for a few hours to soften debris. This greatly reduces the time spent scrubbing, especially if anyone in the house lets water from the faucet run while cleaning stubborn food debris.
Another appliance that uses a great deal of water is the dishwasher. Wait until it’s full before cleaning the dishes. Running dishwashers only when they have full loads can up to 1,000 gallons of water each month. New dishwashers are made to clean dishes thoroughly. It isn’t always necessary to rinse dishes before loading.
Sometimes people rinse dishes so thoroughly that it’s almost as if they’re washing the dishes before letting the dishwasher have a turn. This is extremely wasteful and uses a lot of water because you’re essentially washing each dish twice. If an older dishwasher isn’t capable of cleaning the dishes unless the items are spotless beforehand, you may want to consider getting rid of the appliance or replacing it with a newer model. Call a plumber to ask about installing a new energy-efficient dishwasher.
You can also save water by keeping garbage disposals clean and in good repair. A solution of bleach and hot water is a good way to clean the appliance without overly harsh chemicals. Baking soda reduces odors. Remember not to empty kitchen grease or cooking oil into your disposal. Grease and fat solidify as it cools and sticks to blades and pipes. Sticky residue forces every part of your garbage disposal to work harder and leads to more frequent repairs. You can also save gallons of water by only using the garbage disposal when necessary. If you start a compost pile for food scraps, you may have very little reason to use your disposal.
Hot Water Heaters
Another excellent way to conserve water is by keeping your water heater in good condition. It should be tested and flushed regularly. Autumn is a good time of year for water heater maintenance in Arlington, TX, because a drop in temperatures usually corresponds to an increase in hot water usage. If your household has a traditional water heater, wait at least 10 minutes between showers. This conserves hot water and lowers the risk of lukewarm or cold water halfway through a shower.
Changing the design and location of water heaters, heat pumps, and boilers can have a significant impact on water usage. Letting the water run while waiting for it to reach appropriate temperatures is very wasteful. Simply shortening the distance hot water must travel can help. Hot water takes longer to arrive when the heat source is located far from the outlet. Projects involving significant changes to your hot water system are jobs for professional plumbers.
Ask your plumber about a recirculating pump that transports water to an outlet while simultaneously transporting cold water back towards the heat source. Water isn’t wasted because hot water is systematically pumped to the fixture before it’s needed. These pumps are often activated with switches or sensors.
Water-efficient shower systems take several factors into accounts, such as energy to heat and transport water, showerhead design, and the smallest possible length of pipe from the hot water source to the fixture outlet. All hot water pipes should be insulated to minimize heat loss during delivery. Consult your local plumber to find out if your hot water system can be fitted with a demand-driven recirculation system.
On-Demand Hot Water Heaters
On-demand water heaters, sometimes called tankless water heaters, provide hot water when it’s needed. Since they don’t store warm water, they don’t waste energy keeping water hot when it isn’t being used. Cold water runs into a tankless heater powered by gas or electricity. Some homes may need more than one tankless hot water heater because a single heater can’t provide enough hot water for multiple activities at once, such as showering and running a dishwasher simultaneously.
Even with multiple on-demand heaters, homes may see up to 35% savings on energy bills after switching from a traditional water heater. It’s best to call a professional plumber to install tankless heaters because it also involves new gas pipes, altered ventilation systems, and new wiring.
Water Reuse Systems
Water reuse systems, also known as greywater reuse systems, make use of the runoff from showers, washing machines, and sinks. Laws and ordinances governing greywater use vary, but your local plumber in Arlington, TX, will know what systems are allowed and appropriate in your area. Rain harvesting is a simple type of water reuse system. Rainwater collected in barrels can be used for watering gardens or lawns and other outdoor uses.
Call the professional plumbers at Benjamin Franklin Plumbing of Fort Worth for help with all of your home’s plumbing needs. They can also offer advice on upgrading appliances and plumbing infrastructure in your home in Arlington, TX, to improve your household’s water efficiency and reduce monthly water and energy bills. | <urn:uuid:dd70a644-ef73-41f2-9411-d9ca561cca58> | CC-MAIN-2023-40 | https://benjaminfranklinplumbingfortworth.com/plumbing-blog/the-essential-role-of-a-plumber-in-water-and-energy-conservation-arlington-tx/ | 2023-09-28T18:18:28Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.93526 | 2,521 |
Just in Time for Halloween: Justice Finally Served After Horrific Crash Five Years Ago
A Florida jury has convicted John Goodman of DUI manslaughter — for the second time. The first conviction for the drunk driving crash was reversed because of juror misconduct.
Ultra-wealthy Goodman faces up to 16 years in prison for causing the drunk driving accident that tragically took the life of 23 year-old Scott Patrick Wilson.
The 51 year-old Goodman has repeatedly avoided accountability for the gruesome collision where he ran a stop sign in his Bentley convertible and plowed into Mr. Wilson’s Hyundai Sonata. Mr. Wilson’s car flipped over into an adjacent canal where the recent engineering graduate drowned.
Goodman then fled the scene, leaving the young man to die at the scene. He did not call 911 until an hour later. His blood alcohol content (BAC) was more than twice the legal limit in Florida when he was tested three hours after the fatal DWI auto accident.
Justice Prevails Over Wealth in Drunk Driving Case
oodman has always tried to avoid responsibility for the deadly crash.
Most notably, the millionaire attempted to adopt his 42 year-old
girlfriend as his daughter to protect his assets from a wrongful death
lawsuit filed by Mr. Wilson’s parents. Fortunately, the courts rejected
this shockingly deceptive plan to thwart justice.
avoided accountability when the appellate court overturned a March 2012
conviction for DUI manslaughter and vehicular homicide. A juror failed
to disclose relevant information about his ex-wife’s DUI arrest that
impacted his eligibility to serve on the jury, purportedly with hopes to profit off of the high profile case. While he awaited his second trial, Goodman was released on a $7 million bond and paid $2,000 per day
for monitoring by the Palm Beach County Sheriff’s Department.
The substantial wealth of the polo player, who acquired his fortune from
the sale of his family’s Texas AC manufacturing company, could not buy
off justice permanently. Goodman is likely to receive the same
16-year sentence he did in the first trial. His insurance company has
paid Mr. Wilson’s parents a $40 million settlement.
No Refusal Weekend Announced By Tarrant County District Attorney’s Office
This Halloween weekend from Friday night at 9:30 p.m. through Sunday morning at 5:30 a.m., for the first time, has been added to the list of “No Refusal” Weekends. Police officers will use search warrants which enable them to draw blood from drivers who have refused the standard breath test after arrested for DWI. Those people charged will face fine, jail, and have their names published on the DA;s web site. All weekends during our Stock Show have also been added to the list. I’d like to see every weekend — and every day during the week — be included to stop catastrophes like this one from happening so routinely.
Join Bill Berenson at Walk Like MADD
The Goodman case is a reminder that one person’s poor choice to drink and
drive can result in the tragic death of a promising young person. At
Walk Like MADD, we stand together to demand accountability of drunk
drivers and to end these senseless deaths and injuries.
Berenson Law is a sponsor of the Walk Like MADD
event, where I have been asked to speak to participants. This important annual event raises money and awareness about the consequences of drunk
driving, with the goal of one day putting an end to DUI accidents. Join me at Walk Like MADD at Ridgmar Mall this Saturday, November 1st, to lend your support in the fight against drunk driving.
If you have been injured by a drunk driver, Berenson law can help you reach justice. Call us at 817-885-8000 or toll-free at 1-888-801-8585 for a free consultation. | <urn:uuid:5e6073da-eb62-4a83-be0e-9376267af73b> | CC-MAIN-2023-40 | https://berensonlaw.com/millionaire-polo-player-from-p/ | 2023-09-28T18:58:26Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.958052 | 826 |
The disk space feature displays the full capacity of information that you could have on the website hosting server at any time. With a desktop computer, for example, this is the overall size of your hard drive or the overall capacity of all of the hard disks in case that your PC has more than 1. Exactly as your space on a personal computer is shared between installed applications, documents, your music and the like, the server hard disk space is typically divided between website files, databases and e-mail messages. Each file, folder or e-mail uses a little storage space on the server, so you should consider multiple factors, not just the size of the files that you will upload. For instance, getting sizeable e-mail attachments or running a script-driven website in which the user-generated content material is located in a database will also affect the hdd space you are using.
Disk Space in Website Hosting
With our website hosting
plans, you'll never be worried about disk storage. While most companies generate accounts on a single server and eventually all the server disk storage is in use, we have applied a cloud web hosting system where the files, e-mail messages and databases are taken care of by distinct groups of servers. As a result, every single machine performs better because only one type of processes is functioning on it, and the disk storage is virtually limitless because we will always install extra servers or hard drives to the cluster, based on whether we want more processing power or perhaps more space. You will never deal with a scenario in which you can't upload more files for the reason that there is no available hard disk space on your server, that is a matter you can encounter with other providers. When you use our hosting services, you can be sure that shortage of space won't be an issue for the growth of your websites.
Disk Space in Semi-dedicated Servers
Considering that all our semi-dedicated server
plans are very powerful, we've decided not to restrict the disk space characteristic when we have designed them. Our idea is that when you purchase a powerful plan, it is quite possible that you've got a large amount of website data, therefore each and every semi-dedicated server plan provides you with limitless disk capacity, which will help you center on developing your web sites not worrying whether you'll fit in some allowance. Your hosting account will be created using a cloud website hosting platform in which the emails, files and databases have their own groups of servers, hence not only will the machines perform much better since only a single type of system processes will operate on them, but also you'll never need to worry about the disk space because we'll add as many servers or hard disks to each cluster as needed.
Disk Space in VPS Servers
For all our VPS servers
, our company offers a lot of disk space for your content that matches the other server features, consequently a higher plan comes with a higher quota. You'll be able to use the space as you can see fit, since there are no pre-defined quotas for your web site files, emails or databases - all of them share the whole disk space of the server. Still, when you prefer to have some limits, you are able to get your VPS plan with cPanel or DirectAdmin as the hosting Control Panel, and you'll be able to create hosting accounts with a fixed amount of disk space for every single domain name that you host on your server. In case you want more storage space at some point, you are able to quickly upgrade your plan with a few clicks and the extra features will be included with your current account, so you won't be expected to move anything at all and your sites will stay operational.
Disk Space in Dedicated Servers
All our Linux dedicated service
have numerous HDDs to suit the computing power that you'll get, which means that you'll never need to be worried about not having enough hard disk storage. The drives can be used in RAID, meaning that a drive can function as a mirror of another drive so as to make sure that all your info will be protected, alternatively you can use it separately for even greater complete storage capability. Many hundreds of gigabytes of hard disk space will be available all the time, thus you'll be able to manage enormous sites, upload big files or even keep a copy of your own archive. Considering the fact that a dedicated server is the most powerful kind of web hosting, you'll be able to upload/download files with extremely fast speeds. When necessary, we also provide you with the option to add more drives and employ even further storage for your data. We offer 3 hosting Control Panels with our dedicated servers - when you use Hepsia, all domain names will share the full server space and they will be operated in a single place, while with cPanel and DirectAdmin you will have the possibility to create distinct web hosting accounts with certain disk space quotas for every single domain hosted on the server. | <urn:uuid:03095456-6c0c-4169-b2bc-76b26f986ad8> | CC-MAIN-2023-40 | https://bereveal.com/hosting-definitions/disk-space/ | 2023-09-28T17:22:16Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.953956 | 1,019 |
Inspiring Entrepreneurial Spirit and Creative Thinking
The Flemming Creativity, Entrepreneurship, and Economic Development Center (CEED) Center was established in the fall of 2011 as part of the Gaige Technology and Business Innovation Building.
The mission of the Flemming CEED Center is to inspire an entrepreneurial spirit and innovative thinking in the Pennsylvania State University Berks community. The Flemming CEED Center fosters economic growth and development in the Greater Reading area through technology-based solutions, human capital development, and enterprise creation. The Flemming CEED Center provides student entrepreneurs with an incubator in which to develop their startup ideas. The Center provides mentoring from faculty, as well as volunteers from the local business community. The Flemming CEED Center programs include Creativity Training Workshops, 3D Printing Workshops, Speaker Series, the Customer Discovery Lab, the STEM Business Idea Challenge, and the Student Enterprise Award. | <urn:uuid:5aed7451-2a37-4a44-b300-5839a5ea9dc4> | CC-MAIN-2023-40 | https://berks.psu.edu/flemming-ceed-center | 2023-09-28T17:24:34Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.899516 | 190 |
When the sun is shining and the weather is warm, who wants to spend time in an oven-warmed kitchen? Thankfully, there's a delicious solution to your summer cravings—no-bake recipes featuring the goodness of fresh berries from California Giant Berry Farms. Whether you're looking for a light and refreshing dessert or a sweet snack, these no-bake berry recipes are sure to delight your taste buds and keep you cool all season long!
No Bake Berry Tarts
Create elegant no-bake berry tarts with minimal effort! Use pre-made tart shells or create a simple no-bake crust using crushed graham crackers and melted butter or pecans and dates. Fill the tart shells with a variety of fillings from our recipe database, from a Greek yogurt filling to a dark chocolate blackberry filling.
Savor the taste of summer with these irresistible no-bake berry bars. Bursting with the vibrant flavors of fresh berries, each bite is a delightful blend of sweet berry goodness. Whether you're enjoying them as a quick snack or sharing them at a gathering, these no-bake berry bars will be a summertime hit!
Elevate your desserts with our fresh berry parfait recipes. Layers of delicious filling perfectly complement the juicy sweetness of fresh berries, creating a harmonious balance of textures and flavors.
Embrace the lazy days of summer by indulging in these no-bake berry recipes that make the most of fresh California Giant Berry Farms strawberries, blueberries, raspberries and blackberries. Which recipe will you make first? | <urn:uuid:31184a58-50d9-4021-8989-9f34256de0c2> | CC-MAIN-2023-40 | https://berrybuzz.calgiant.com/our-best-no-bake-berry-dessert-recipes | 2023-09-28T17:25:42Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.874647 | 332 |
We are providing here 25+ GTA 5 Cars – That’s the world’s fastest cars in GTA 5. Also, it’s a modern, luxury, sport, super vehicle… and you know there are tons of cars in GTA 5 for you to steal drive, and destroy, however, But if you are looking for some fastest & new cars. So we got you covered, this car pack is available for download to everyone. and you should download it. for installation read the below instruction.
- Add-On Cars
- Full new cars
- High-Quality model
- HQ car body and interior
- Animated exhausts
- Animated engine and exhaust v vibrate
- Working Lights
- Working Dials
- HQ Texture
- Breakable Windows
- Good mirror reflections
- Hands-on Steering
- Collision deformation
- Functional speedometer
- Custom handling setting
- And Much More…
How to Install GTA 5 Cars:
- Download the “Cars” from here.
- Then extract the RAR file.
- And open the extracted folder
For more installation instructions read inside file README! notepad.
Just read & install, then enjoy the fastest cars in GTA V.
How to Spawn Vehicles:
- You have to install Add-on Spawner Menu in your GTA 5 then you can find any [add-on] vehicle very easily.
- Click Here for downloading and installation
We have a lot many comments from our supporters who want the fastest cars in GTA 5 and the car pack is ready for you. So friends thanks for the support keep it more and enjoy the fastest cars in GTA V more than more. We are always available for you. and, you can download more best mods car packs for GTA 5 & GTA 4 from our website. Click Here to check it out.
Disclaimer: We do not intent to infringe any intellectual right to artist rights or copyright. If you feel any of the content posted here is under your ownership just contact us and we will remove that content immediately. Or if you require a suitable credit please let us know. mods and any other information presented is intended only to familiarize users with the materials that may be of interest to them. | <urn:uuid:3183b72d-3b64-474a-96b5-4a48511be17c> | CC-MAIN-2023-40 | https://best-modding.com/2021/08/gta-v-cars-pack-all-new-2021-25_89.html | 2023-09-28T17:53:34Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.904896 | 472 |
Dehumidifiers come in a wide variety of sizes. Some of the most compact and portable models use a method of dehumidification based on the Peltier Effect or thermoelectric cooling, hence the name Peltier dehumidifiers (sometimes also called thermoelectric dehumidifiers).
The main difference from the more common compressor models is their size and coverage. Peltier dehumidifiers are particularly popular for their small size, quiet operation, and inexpensive price. So, if you need a dehumidifier for a small room or other small space, without a really excessive amount of moisture, then you may want to look into buying a Peltier dehumidifier.
They are cost effective, but they tend to only work well in situations like I described above. For larger spaces and really high humidity refrigerant and desiccant dehumidifiers tend to perform better.
Let’s review how Peltier dehumidifiers work, so you can better understand how these compare to other types of dehumidifiers.
How A Peltier Dehumidifier Works
The Peltier Effect
It is named after French physicist Jean Charles Athanase Peltier who discovered that a voltage of electricity can be converted to a temperature difference. Prior to this discovery, it had been known that the converse of this was true—that a difference in temperature can be converted to electricity.
The thermoelectric cooling technology involved in Peltier dehumidifiers is based on the Peltier effect. Electricity runs through the Peltier module which creates a temperature difference between its two sides. One side of the module is hot while the other side of the module is cool. This difference in temperature leads to moisture removal from the air.
Most Peltier dehumidifiers have a very basic design. They are mainly composed of a Peltier module with two heat sinks, and a fan which facilitates air movement. The fan draws the air into the intake on the front of the unit and out through the exhaust commonly found on the top.
The cold side heat sink is located where the air enters and moisture is removed. Below is a tank that catches the water collected. It’s usually big enough to hold at least two days worth of dehumidification. The hot side heat sink is on the back where the air passes through before coming out of the exhaust.
A majority of thermoelectric dehumidifiers feature simple controls with a single button for the on/off power switch. Other larger models may also come with a humidistat to adjust the humidity to the user’s desire, or more controls for the fan speed or operation mode.
Humid air is drawn by a small fan on one end of the unit and enters through the other, colder front side. As the air cools, the moisture condenses and drips down to the water tank. The cool and dry air then passes through the hot side. Warmer, dryer air exits through the exhaust.
This process is not that different from that of a refrigerant-based dehumidifier, but instead of using a compressor to cool down the coils and remove moisture from the air, a Peltier dehumidifier converts the electricity into a temperature gradient between two sides of the module. As is the case with compressor dehumidifiers, the efficiency also decreases in cooler temperatures.
Advantages of Using a Peltier Dehumidifier
Peltier dehumidifiers can come with a capacity as small as 250ml per day. They are incredibly light and compact. Weighing just a little over 2 lbs, the tiniest models are about 20 times smaller than the typical residential dehumidifier. Due to the size, they are suitable for small spaces and less severe moisture problems. They work very well in smaller areas such as a bedroom, bathroom, laundry room, and even boats or RVs.
Perhaps the best feature of Peltier dehumidifiers is the whisper-quiet operation. This is a real advantage over compressor-based and even desiccant dehumidifiers. The only part which produces noise in this type of dehumidifier is the fan, whose sound is usually more pleasant. Compressors produce a buzzing noise when operating, while the fans on both the compressor and desiccant types are much larger than the small 12-volt fans used in thermoelectric dehumidifiers. They can produce as low as 30 to 40 decibels on operation. Because of this, they are ideal for living or sleeping areas where you need a quiet dehumidifier.
Ease of Use
A Peltier dehumidifier generally has a very basic design and few parts that can break. Almost anyone can operate this dehumidifier. There are only a couple buttons (most units even have just one button) with a simple design and label. There is no control panel or digital display you will have to decipher. One push of the button and the unit will start dehumidifying. It will only stop automatically when the tank is full or if you manually shut it off.
When the tank is full, the FULL indicator light will illuminate until you remove the tank and empty the water by hand. The tank can be found on the bottom part of the unit. Simply slide out the tank from the front or back (or one side for some units), remove the lid or plug, and pour the water into the sink or drain. This is all the maintenance you’ll need to do for your dehumidifier.
Electric cost is often a concern for homeowners when using a dehumidifier. Well, a Peltier dehumidifier consumes very little power, as low as 20 Watts for the smallest units. As long as you use it in the recommended area, you’ll feel a significant change in the relative humidity and barely notice it in your electricity bills. At 22 Watts power draw, your dehumidifier will only consume a total of 0.5 kilowatts after 24 hours of use.
Disadvantages of Using a Peltier Dehumidifier
Peltier dehumidifiers are great if they’re used in the correct type and size of space. But they are also fairly limited in terms of capacity and coverage.
Moisture Removal Rate
As mentioned, thermoelectric dehumidifiers have very small capacity, typically ranging from 250 ml to one liter per day (or around 0.5 to 2 pints). A full-size desiccant desiccant dehumidifier has a rate of 10 to 20 pints per day, while the most common compressor-bases dehumidifiers for homes can remove 35 to 50 pints of moisture per day. This definitely limits the applications for a Peltier dehumidifier.
Area of Coverage
Because of their small physical size and moisture removal capacity, Peltier dehumidifiers can only be used in very small spaces. They are not a replacement for the bigger and more expensive compressor or desiccant dehumidifiers. They will make little to no change on humidity levels in a large room. Even the bigger units like the Eva-Dry EDV-2200 may not be enough for an average-sized bedroom.
Take note that most models indicate the recommended coverage area in cubic feet, instead of the more common square footage in other dehumidifiers. This means you need to measure the height, width, and length of the room, and multiply everything. So, if your ceiling is 10 feet high, then 2200 cubic feet can only cover a 220 square feet room. That’s why, the most common Peltier dehumidifiers are only ideal for the smallest bedrooms and bathrooms or other small and enclosed spaces.
Peltier dehumidifiers are inexpensive because they are made with inexpensive and often low quality components. Peltier modules typically last very long, but those that are used in dehumidifiers are cheap and of low quality. The small fan is usually the first to break. However, it can easily be replaced with a basic 12-volt fan used for computers.
This can both be an advantage and disadvantage for the thermoelectric dehumidifier. On the one hand, it’s cheap, small, and easy to operate. But on the other hand, it has a lower quality construction and cheap parts. But then again, replacement parts are easy to find in the rare case that any of them break. So really, it’s up to you and how often or how long you’ll use the dehumidifier.
If you want the best value for your money in terms of the amount of moisture your dehumidifier can remove, then a Peltier dehumidifier may not be the right investment for you. The typical Peltier type is around ten times cheaper than the average 50-pint compressor dehumidifier. Meanwhile, the former has a capacity of about 0.5 pint, which is a hundred times smaller than 50 pints. Obviously, you’ll get a higher moisture removal rate per dollar invested in a compressor dehumidifier.
However, operating costs are a different conversation. While the same Peltier dehumidifier draws around 20 to 25 Watts, the 50-pint will consume 500 to 700 Watts per hour of operation. If you have a very small space, then a full-size compressor model may be a bit overkill, and not to mention, wasteful of energy. And so, again, it’s up to your own judgment if the Peltier is the right one for you.
Peltier dehumidifiers are popular among RVers for their tiny size and easy, quiet operation. They’re also common in bathrooms and small bedrooms. While there are mostly positive reviews, a lot of the criticisms root from the consumer’s unrealistic expectations.
Keep in mind that thermoelectric dehumidifiers are specifically designed for very small spaces. Manufacturers specify this on the product description. You cannot expect it to work in the same capacity as a compressor dehumidifier. Opting for the smaller Peltier type just to save some money now will actually cost you a lot more in the long run.
It’s important that you know exactly what you need before you make a purchase. How big (or small) is your space? How much moisture do you need to get rid of? These are only some of the factors you must consider when choosing a dehumidifier. If you need help finding the best Peltier dehumidifier model for a specific room or application, we have these guides for you. | <urn:uuid:b0035dab-0cba-4487-a8b7-cd712b8616bc> | CC-MAIN-2023-40 | https://bestdehumidifier.reviews/how-do-peltier-dehumidifiers-work/ | 2023-09-28T17:20:51Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.914887 | 2,263 |
Packed full of action and adventure, Faptitans.com brings you to the epicenter of a relentless MMORPG. From hordes of dangerous enemies, to thrilling quests and trials, this game merges strategic team-play with intense real-time PvP battles. Gather your own titanic forces from diverse hero classes and unlock powerful abilities as you enhance your strategy against countless foes!
Immerse yourself in an expansive fantasy world as you battle hordes of fierce monsters, familiarize yourself with enigmatic faction leaders, and venture through forgotten dungeons in search of legendary treasures. Experience the thrill of assembling and customizing a powerful team capable of obliterating their competition!
Take on all-new lands with an evolved weapon system as you engage everyone from ferocious dragons to ancient undead. Embark on action-packed missions ranging from eradicating giant insects to executing daring raids against Viking ships. Defend cities from hordes of goblins and sail across perilous seas while learning the secrets behind alluring artifacts!
Unlock unique abilities by advancing through levels with friends or alone. Customize heroes to fit your own battle plan – upgrade weapons, craft armor sets, find artifacts – allowing Faptitans only limit to be your imagination. The RPG fun continues in daring raids against bosses as you race for rewards!
At FapTitans, you get more than just an epic gaming experience – it’s an MMO masterpiece that features rich graphics, exciting story content, and innovative play mechanics every step of the way. With immersive storylines for all types of players – casual or hardcore – explore treacherous dungeons filled with challenging puzzles and test your skills in RAIDs against formidable bosses! Whether playing solo or in groups up to ten members, fighting enemies become even more fun when supplemented with special items like magic potions or hp enhancement items! Best yet – strike streaks to earn additional loot drops throughout the week! | <urn:uuid:c0122f7c-406f-4798-9495-f3940b786a3e> | CC-MAIN-2023-40 | https://besthdporn.me/faptitans/ | 2023-09-28T17:27:37Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.905655 | 375 |
At Lubed.com, you can experience the hottest girls indulging in wet and messy sex like never before! Our high quality videos will give you a sensuous visual pleasure that is sure to spice up your life. From exotic locations like beach-front cabanas to warm rain-soaked showers, experience a new level of passionate lovemaking with hot models in which everything is drenched in lube!
Our videos feature some of the world’s most beautiful women performing steamy sexual acts that are both seductive and visually pleasing. Get ready to witness some explosive moments as these gorgeous ladies get really down and dirty while they engage in wildly erotic play. Our girls take no prisoners and use every part of their thrilling bodies to get each other off! Let yourself melt into their sticky embrace as passion levels skyrocket during incredible orgasms!
Lubed.com allows you to explore your fantasies with our handpicked selection of super-hot models who ooze sensuality with every move they make. Enjoy watching as these lusty vixens strip off their clothes before smothering each other in thick streams of lube. Watch them slide up and down each other’s slippery bodies while engaging in wild clashes between pleasure and pain. Be prepared for intense scenes where large amounts of oil and lube are poured all over their smooth skin turning the action even hotter!
Expect an amazing adventure through the steamy world of sexy women getting hot, wet and incredibly messy! Go beyond the confines of traditional pornography by watching these lovely ladies enjoy long and fiery encounters that lead to fantastic climaxes. Why settle for normal when there’s so much more out there? Experience mind blowing sexual energy unlike any other at Lubed.com! | <urn:uuid:e027ed72-dd09-4207-9575-44005b9cf3a3> | CC-MAIN-2023-40 | https://besthdporn.me/lubed/ | 2023-09-28T18:17:56Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.928866 | 353 |
Many people say that beginning a home-based business is hard, but that isn’t true. Educating yourself about different business opportunities for your home based business can help you decide whether devoting some hard work to establishing a home based business is right for you. Home businesses just require you to have good information. The things this article will go over can help your work from home business get started.
If an Internet connection is used to run your business, you can deduct it on your taxes. You can deduct some of the cost from your profits, but you cannot claim more than 50% if you also use it for personal use.
Focus your business efforts on maintaining the happiness of your regular customers. It is easier to generate income from repeat buyers than to attract new ones. Happy customers will come back for more.
Take short breaks during the day and avoid getting too absorbed in household personal activities. Don’t begin complicated home improvement projects or take long, personal calls. Keep your body and mind fresh by taking breaks to do other things such as exercising or going for a short walk.
Become a part of a forum of home business group online. This lets you network, learn and share your expertise. You might even find some potential partners or some leads.
Go on the internet and get things you need at your office at a good price. There are so many options when it comes to saving money on your purchases. Use the information to create the best vendor list possible. To buy your supplies this way, you need a business license.
In conclusion, it does not need to be hard to begin a home based business. It is a lot of hard work but is a very achievable goal. The tips contained in this article will provide you with the information needed to be on the road to owning your own profitable online business.
There are tremendous opportunities for small businesses and social entrepreneurs to support their communities through community foundations, donor advised funds and other means of giving back. Find the neighborhoods in
Chicago, Illinois where you can make the most impact on education in the community. | <urn:uuid:f6173204-3038-41b3-85a3-cbcf569990e1> | CC-MAIN-2023-40 | https://besthomebasedsmallbusiness.com/2022/08/ | 2023-09-28T18:57:32Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.955282 | 423 |
It’s no secret that the best way to get a good, quality night’s rest is to have a comfortable bed. Many consumers put off buying a new mattress until their old one is simply no longer functioning. The best thing to do when you start to notice your mattress is becoming uncomfortable is to buy a new one, not put up with the old one. Your quality of sleep is directly impacted by the comfort of your mattress, so be sure that you are investing in a good night’s sleep. Here are just a few surprising benefits of a comfortable mattress in D’Iberville, MS
People who get a good night’s rest, and who are able to sleep for at least seven hours per night, produce more leptin than those who don’t sleep well. Leptin is one of the hormones that regulates your food ingestion, helping you to feel full when you’ve finished a meal. Those who have low leptin levels find that they are hungrier more often, and tend to crave fattier, more caloric foods.
Protects Against Disease
Your quality of sleep can control how your immune cells behave, and what your current level of antibodies is. A chronic lack of sleep will negatively impact your immune system, making you more susceptible to diseases. A good night’s rest can also ward off chronic conditions, such as heart disease and diabetes. The less you sleep, the higher the risk for inflammation throughout your body – which can in turn increase your risk for a heart attack, high blood pressure, or a stroke.
Improves Memory And Creativity
Repeated studies have shown that those who have a higher quality of sleep are able to process memories made during the day much easier. Those who do not receive an adequate amount of sleep may find that their ability to recall events from that day, or any new thing learned, difficult if not impossible. A good night’s rest is also linked to increased creativity, helping people problem solve in more creative ways and making it easier to relate to others on an emotional level.
For more information about purchasing a comfortable mattress in D’Iberville, MS., contact Mattress Direct at | <urn:uuid:c7f09759-32bf-4a10-9911-b6deb6dad964> | CC-MAIN-2023-40 | https://bestonlinebuy.org/surprising-benefits-of-a-comfortable-mattress-in-diberville-ms/ | 2023-09-28T18:08:13Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.949374 | 450 |
How to Fix Office Chair Tilt
If you’ve been sitting in your office chair for years, and you’ve noticed that your chair is no longer tilting the way it should, there are a few steps you can take to fix it. To begin with, you’ll want to replace the mechanism that controls the tilt.
Tighten the fasteners
If your office chair tilts when you lean on it, you should try tightening the fasteners in your chair. This will help to keep it upright and will also prevent your back from straining. It may be necessary to replace the seat plate or the wheels on your chair. The seat plate is the steel frame that is under your seat cushion. It can become loose or broken from everyday use. Depending on the brand and model, the cost of replacing a seat plate may vary.
You can easily fix your tilting chair if you follow the steps described below. To determine the cause of your problem, you should flip the chair over and check the fasteners. If the bolts and screws are missing, you should replace them with a new set. These are often available from your local hardware store.
If the wheel bearings are worn out, they can create a wobbling effect that makes your chair tilt. Usually, this is a symptom of a broken caster. A replacement wheel can be found at your local office supply store. Using an adjustable wrench, you can tighten the bearings so that your chair will not wobble.
Another common problem that can cause an office chair to lean is a missing or rusted bolt. If the bolts are missing, you can replace them with a screwdriver or an adjustable wrench. However, this is not a fix for a rusted or broken caster.
When your chair tilts too far, there are usually several parts that need to be replaced. First, you should check the casters on the bottom of the chair. Some casters are metal and others are plastic. If a caster is plastic, you can replace it with a metal caster. You should also check the bearings on the wheels. They can be worn out over time and can cause a locking effect.
Another issue that can cause your chair to tilt is a loose seat plate. A seat plate is a thin steel frame that is underneath your seat cushion. Usually, this is painted black. There are a number of screws that go into the seat plate. When they are loose, the seat can be pulled away from the bottom of the seat cushion.
Lastly, you can also check your armrests. If the armrests have fallen apart, they can be removed with a screwdriver. Alternatively, you can remove them with your fingers or a hammer. If you do not have a hammer, you can buy a pliers set.
Before you decide to repair your office chair, you should look over the user manual to determine which fasteners are missing. Often, the manual will have a diagram that will show you which fasteners are attached to which parts of your chair.
Replace the tilt lock mechanism
The tilt lock on an office chair is a key feature to the height adjustment and recline features of the chair. If the lock does not work properly, the user may experience pain and discomfort. This can be caused by a broken spring or a malfunctioning lever. Depending on the problem, the user can either fix the issue themselves or have it fixed by a professional.
In order to repair the problem, the first step is to remove the tilt lock. Tilt locks are located at the back of the chair. They can be removed with a screwdriver. Once the mechanism is free from the seat, the tilt lock can be cleaned with a paper towel or rubbing alcohol. A small amount of machine oil can also help the parts move more smoothly.
You can also adjust the position of the tilt lock. If you have trouble reclining, try moving the tension knob in a clockwise direction. For a reclining chair, the ideal angle is 135 degrees. However, if you have difficulty reclining, this can be due to a damaged recliner spring or a malfunctioning lever. Using a Q-tip, you can lubricate the parts.
Another common problem is when the tilt lock is stuck. To avoid this, it is important to make sure the correct components are installed. One way to check for this is to lay the chair on its side for a few minutes. After that, it should be possible to unlock the lock. Alternatively, you can buy a new tilt lock from a store.
Some manufacturers use a single lever to lock and unlock the tilt of the chair. Others use a paddle. Regardless of the type, the tilt lock is essential to the height adjustment of the chair.
If the tilt lock on your office chair is broken or worn out, you will need to replace it. Tilt locks can be replaced by the user, by a service shop or by an online retailer. Be sure to consult the owner’s manual of the chair for specific instructions.
Choosing a replacement tilt lock is important, as different chairs use different types of locks. It is best to buy a replacement that matches the model of your chair. You can also have a service shop install it for you.
Buying a replacement can be done on the Internet or through your credit card. Typically, tilt lock replacement comes with a warranty. You can purchase a replacement from Amazon Prime or other retail websites. Make sure to read reviews before purchasing a replacement. When buying a tilt lock, choose a product that has a high rating.
While you can easily fix your tilt lock issues on your own, it is a good idea to hire a professional if you are unsure of how to do it. Otherwise, you could cause more damage to the chair. | <urn:uuid:b0d06f2f-af92-4539-b054-0e87b2c09fb7> | CC-MAIN-2023-40 | https://bestproductreviewscenter.com/how-to-fix-office-chair-tilt/ | 2023-09-28T18:37:17Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.945212 | 1,187 |
Your sales representative resume objective statement is a concise summary of your skills and strengths for the sales rep job.
You should therefore, highlight qualities like people skills, energy, and ability to help link customers with the right product.
This can compel a hiring manager to read all parts of your resume/CV.
Having a great objective statement in your sales representative resume can be crucial to your landing the job.
Your objective statement should be a representation of what the company stands for, and illustrate to the employer why you are the ideal candidate to represent their products.
The objective should describe your enthusiasm and qualifications, emphasizing why you want to work for the company you are applying to.
Describing existing interest or previous experience showing prior knowledge of the type of goods you are applying to sell is a great way to stand out of the crowd.
Here are some strong compelling sales representative resume objectives you can study and use in writing your own:
Top 22 Sales Representative Resume Objective Examples
1. Highly energetic person with great personality and motivation, and with a desire to succeed, seeking a Sales Representative position with ABC company; to utilize communication skills and love for all things fashion.
2. Experienced extrovert seeking opportunity as Sales Representative with XYZ Company, which will benefit from strong working knowledge of fishing and outdoor sporting equipment.
3. Applying for work as Sales Rep with Sears, bringing the benefit of 7 years of experience building effective business-to-business relationships in the clothing industry
4. Looking for Sales Person position at Random Music Equipment Store; to share passion and knowledge of speakers, stereos, and other consumer audio equipment using speaking skills to relate with customers and make sales.
5. Ambitious individual desires to work at Regarde Equipment Shack as a Sales Representative; bringing college qualifications, sales and people skills, and sales experience in a similar line of business.
6. Desirous of the position of Sales Representative at Berthas Pharmaceuticals; possess pharmaceutical knowledge, sales qualities, and great communication skills.
7. To obtain a position at a company with high organizational direction that will benefit from sales experience, positive interaction skills and industry contacts acquired from twelve years of experience, thereby ensuring sales results.
8. Sales Representative seeking position where 10 years of sales experience can be put to use to improve sales bottom line and increase company revenue.
9. Applying for Sales Representative post at Rebock Stores where skills and expertise can be utilized for increased profitability, quarterly sales rise, and yearly increased sales volume.
10. Looking to join a dynamic sales team as Sales Representative; bringing qualifications and experience to create potential sales growth and increased customer patronage.
More Sales Representative Resume Objective Examples [11-16]
11. Desirous of position of Sales Representative with XYZ Company; seeking challenging environment, applying creative problem solving skills to achieve optimum utilization of resources, and making maximum profit.
12. Motivated Sales Rep seeking an environment that offers a greater challenge, increased benefits, and the opportunity to advance company efficiency and productivity.
13. To obtain position and become associated with a company where utilization of skills is encouraged, and to gain further experience while enhancing the company’s productivity.
14. Seeking work as Sales Representative at Republic Mall; desirous of a challenging position in a high quality sales environment where resourcefulness, experience and academic skills add value to store operations.
15. Sales Representative seeking workplace for communication and people skills, and environment to interact with customers and staff, improving sales and profit margin.
16. To obtain a position at ABC Company as a Sales Person; bringing strong sales skills, marketing background and ability to work with people in best possible ways for achieving company sale goals.
Additional Sales Representative Resume Objective Examples [17-22]
17. Applying for the position of Sales Representative with an internet company, coming with experience in SEO with a proven record of sales results, developing new sales leads, and maximizing internet sales expertise.
18. Determined individual seeking a job as Sales Representative; bringing highly effective communication skills, demonstrable persuasion and negotiation skills, and ensuring consistent achievement of sales targets.
19. Result driven Sales professional looking for opportunity to identify potential sales targets and grow sales base; coming with influence and negotiation skills, and guaranteed success in business-to-business sales, and long-term customer relationship.
20. Sales Representative with documented track record of establishing and growing sales in new geographical territories; with resilient nature and solid work ethic; seeking a position with XYZ Company.
21. To obtain a Sales Rep job that offers a vibrant workplace where solid sales experience and proven customer relationship strengths can achieve challenging sales goals.
22. Team-player with outstanding track record of effectively assessing customer’s needs, closing sales with winning attitude and strong work ethic, excelling at prioritizing projects to achieve maximum sales volume seeking the position of Sales Representative with XXA Inc.
Your objective statement may be the clincher that decides whether your resume gets read or not, which in turn may determine if you get the job or not.
Therefore, your qualifications, skills, and experience as a sales representative should be used in writing the objective statement of the resume to convey value to the employer.
However, make sure your objective statement tallies with the published job description for the role, from where you will learn the kind of sales person the employer is looking for.
This ensures that your resume is given attention to and read.
Each of the sales representative resume objective samples shown above can be of great help to you in writing a don’t-put-me-down resume for your job hunting.>>> Create a professional resume in just 3 steps with the Amazing Resume Builder (it's free!). | <urn:uuid:2713de4c-d111-4718-b8ed-7e6637e2cc5a> | CC-MAIN-2023-40 | https://bestresumeobjectiveexamples.com/top-22-sales-representative-resume-objective-examples/ | 2023-09-28T18:34:58Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.913446 | 1,180 |
Choose Best Roof Box, Racks, Bars
Trending Roof box guide Lists
Check Out Reviews From Best Experts
Best Roof Box, Racks, Bars Reviews
How We Make The Best
Roof Box, Racks Reviews
Frequently Asked Questions
A roof box is a large storage container designed to be mounted on the roof of a vehicle. It is used to store items such as luggage, camping equipment, and other bulky items that would otherwise take up too much space inside the vehicle. Roof boxes are typically made of plastic and are secured to the vehicle with straps or other mounting hardware.
Choosing the right roof box depends on several factors such as the size and shape of your vehicle, the amount of storage space you need, and the type of gear you’ll be carrying.
Here are some things to consider when choosing a roof box:
Size and shape – Ensure that the roof box you choose fits the size and shape of your vehicle. Check the roof load capacity of your vehicle and make sure the weight of the box and its contents don’t exceed that limit.
Capacity – Consider the amount of storage space you need. If you plan to carry bulky items such as skis or snowboards, make sure the box is long enough to accommodate them.
Aerodynamics – Look for a roof box with an aerodynamic shape to minimize wind resistance and noise. A sleeker design can also improve fuel efficiency.
Security – Choose a roof box with a secure locking system to protect your gear from theft.
Durability – Select a roof box made from durable materials such as fiberglass or ABS plastic to withstand harsh weather conditions and rough handling.
Brand and price – Choose a reputable brand that offers a warranty for their products. Consider the price and look for deals and discounts to get the best value for your money.
Overall, it’s essential to consider your specific needs when choosing a roof box to ensure you get the right one for you.
The weight of a roof box can vary greatly depending on the size and type of material that it is made of. Generally, a medium–sized roof box made of plastic will weigh between 20 and 40 pounds, while larger boxes made of aluminum can weigh up to 70 pounds.
There are several reasons why roof boxes are generally more expensive than other types of luggage carriers:
1. Material: Roof boxes are typically made of high-quality materials such as hard plastic or fiberglass, which makes them more durable and long-lasting. These materials are also more expensive than the materials used in other types of luggage carriers.
2. Design: Roof boxes are specifically designed to fit on the roof of a car or SUV, which requires a unique design and engineering. The aerodynamic shape and the locking mechanism also make them more expensive to manufacture.
3. Capacity: Roof boxes have a larger capacity than other types of luggage carriers, which means they can carry more items. This increased capacity also adds to the cost of manufacturing.
4. Brand: Like any other product, the brand name also plays a role in the cost of roof boxes. Premium brands often charge a premium price for their products due to their reputation and the quality of their products.
Overall, the cost of roof boxes is higher due to the materials, design, capacity, and brand name, making them an investment for those who frequently travel with a lot of luggage.
Roof boxes vary in weight depending on which one you choose. The average weight is 20-30 Kg (45 – 65 lbs). That’s only 10kg -15kg less than similar canoe or kayak carriers. roofbox roof mounted luggage carriers are roof top luggage systems, the roof rack mounts to the roof of your vehicle. This allows you to place luggage on your roof without having to purchase an additional roof rack system..
When it comes to carrying luggage on the roof of your vehicle, there are a few additional items you may need:
Roof rails or crossbars: These are the foundation for attaching a roof box or rooftop bar to your vehicle. Not all vehicles come with roof rails or crossbars, so you may need to purchase them separately.
Mounting hardware: Depending on the type of roof box or rooftop bar you choose, you may need specific mounting hardware to attach it securely to your roof rails or crossbars.
Tie-down straps: Even if your roof box or rooftop bar comes with its own mounting hardware, it’s a good idea to use tie-down straps to further secure your luggage and prevent it from shifting during transport.
Roof protector: To protect your vehicle’s roof from scratches and dings, consider using a roof protector such as a rubber mat or foam blocks.
Weight limit warning sign: In some countries, it’s required to display a weight limit warning sign on your vehicle when carrying luggage on the roof. Check your local regulations to see if this applies to you.
It’s important to carefully read the instructions for your specific roof box or rooftop bar and ensure that you have all the necessary equipment before setting off on your trip.
There are several reasons why a roof box may be a better option than other types of luggage carriers:
More space: Roof boxes typically offer more space for storage than other options like trunk-mounted or hitch-mounted carriers, allowing you to bring more gear with you on your trip.
Protection: Roof boxes are designed to be weather-resistant, protecting your belongings from rain, snow, and other environmental factors that could damage them.
Security: Many roof boxes come with locks to secure your belongings and deter theft, providing an extra layer of security.
Versatility: Roof boxes can be used on a wide range of vehicles, including cars, SUVs, and minivans, and can be easily removed when not in use.
Aerodynamics: Roof boxes are designed to be aerodynamic, reducing wind resistance and improving fuel efficiency compared to other types of carriers.
Accessibility: Roof boxes can be easily accessed from the side or rear of your vehicle, making it easy to load and unload your gear.
Overall, a roof box may be a better option if you need to carry a lot of gear, want to protect your belongings from the elements and theft, and prefer a versatile and aerodynamic option. However, it’s important to consider the weight and size of your roof box, as well as your vehicle’s load capacity and any local regulations, before making a purchase.
Answer: It is generally safe but you should take some precautions to prevent the box from falling off.
While it is technically possible to keep a car roof cargo box attached at all times, it is not always recommended due to the following reasons:
Wind resistance: Keeping a roof box attached to your vehicle at all times can increase wind resistance, reducing your vehicle’s fuel efficiency and potentially causing stability issues when driving at high speeds or in strong winds.
Height clearance: A roof box can increase the height of your vehicle, making it more difficult to navigate low clearance areas such as parking garages or drive-throughs.
Security: Leaving a roof box attached to your vehicle at all times may make it more vulnerable to theft or tampering, especially if it is loaded with valuable items.
Aesthetics: A roof box can significantly alter the appearance of your vehicle, which may be undesirable for some.
That being said, there are situations where it may be practical or necessary to keep a roof box attached at all times, such as if you frequently use it for work or travel. If you do choose to keep your roof box attached, make sure to follow the manufacturer’s recommendations for weight capacity and installation, and periodically check for any signs of damage or wear. It’s also a good idea to remove the roof box when not in use for an extended period of time, to prevent any potential damage or wear on the roof box or your vehicle.
A car roof box is a good option if you need extra storage space for your gear, but still want to sleep in your vehicle or a traditional tent on the ground. A roof box is designed to be aerodynamic, weather-resistant, and secure, and can be easily removed when not in use.
On the other hand, a car rooftop tent is a good option if you want to combine sleeping and storage in one unit. Rooftop tents are designed to be mounted directly on top of your vehicle’s roof and provide a comfortable and elevated sleeping space, while also freeing up space in your vehicle for other gear.
Ultimately, the choice between a roof box and a rooftop tent will depend on your personal preferences and needs. If you need a lot of storage space and prefer to sleep on the ground, a roof box may be the better option. If you want a convenient and comfortable sleeping space that is elevated off the ground, a rooftop tent may be the better choice.
– Take it to a specialist immediately.
– Put in some weatherproofing spray.
– Wait for the leak to stop before doing anything.
– You can load bulky items on top of your car without worrying about them spilling out onto the street.
– Your trunk will take up less space so you’ll have more room to store your luggage.
– Roof boxes are easy to install, even if you’re not mechanically inclined. | <urn:uuid:1c695c52-1e47-488e-a355-e81778b2cb92> | CC-MAIN-2023-40 | https://bestroofboxguide.com/ | 2023-09-28T18:12:54Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.936635 | 1,971 |
Canadians are packing up and leaving at a fast rate, during a traditionally slow period. Statistics Canada (Stat Can) data shows emigration, the act of leaving permanently, jumped in 2021. The past year showed modest gains, rising to the highest level in half a decade. The fourth quarter is what sticks out though, showing a sudden acceleration. Canada saw the largest Q4 volumes of residents leaving since the 1970s.
Canadian Residents Had The Largest Q4 Outflow Since The 1970s
Canadians left the country at a swift pace in a quarter they usually don’t plan a move. Stat Can estimates 16,901 emigrants in Q4 2021, up 215% from a year before. Annual growth doesn’t mean much, due to the outbreak’s base-effect. Don’t let the distortion allow you to dismiss the whole trend though.
Canadian Fourth Quarter Emigration
The number of Canadians estimated to have left and severed residency ties with Canada, for the fourth quarter.
Source: Statistics Canada; Better Dwelling.
Looking at the longer term, this was a huge fourth quarter. The Q4 2021 emigration was still 55.7% higher than the 5-year median for the quarter prior to 2020. It also happens to be the biggest Q4 for people leaving since 1974.
Canadian Emigration Is The Highest Since 2016
Canadian emigration showed modest growth last year, but highlights the Q4 acceleration. There were 55,935 emigrants in 2021, up 191.5% from a year before. Compared to the 5-year median prior to 2020, last year is 7.1% higher. Annual growth sounds more impressive than it was, but the longer term trend reveals it was still the highest volume since 2016.
Population Growth Is Still Positive, But Emigration Is A Problem
It’s important to understand this doesn’t mean Canada’s population isn’t growing. The country’s population is aggressively increasing due to higher immigration. For every person that leaves, Canada has managed to attract several more. Unless you’re only trying to balance your tax revenues, net growth while ignoring rising outflows isn’t a positive.
If Canadians leave in higher volumes for sustained periods, it warrants a deep dive. Just looking for much warmer weather is one thing, since it can’t be changed. However, a structural problem forms if the outflow is due to expensive housing or eroding economic opportunity. In the short term, immigration can patch over the loss of people. If they’re leaving for a reason though, immigrants take a wider look at their options. | <urn:uuid:1f69d2ca-5cdf-4360-abd8-75da4a8b4fc9> | CC-MAIN-2023-40 | https://betterdwelling.com/canada-just-saw-the-biggest-q4-for-residents-permanently-leaving-since-the-1970s/ | 2023-09-28T17:02:21Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.950612 | 550 |
Parimatch 2023 - Registration
Registration is easy and quick - all you have to do is fill in your personal details, accept terms and conditions and create your own password.
Parimatch offers a number of free bets and promotions for its customers. They also run a Loyalty program that helps players boost their balance and improve their winnings.
The website is easy to use
The registration process at Parimatch is fast and easy. All you need to do is follow the yellow sign-up button and enter your contact details. Once you have done that, you will receive a text message that your account has been activated. Then you will be able to access the website and place bets.
You can also use the site to check out sports betting odds. This is an excellent way to increase your winnings. Whether you are betting on football, basketball, tennis, horse racing, or cricket, you can find the best odds with the help of this site.
One of the best things about the Parimatch website is that it offers a lot of customer support. This means that you can get help any time you need it. You can call the customer service team, chat online, or use the live chat feature. You can even send them an email to ask for assistance, and they will get back to you as soon as possible.
Another great thing about the website is that it is available on mobile devices. This is important because most people now do business on their phones. This makes it important to have a website that works well on these devices.
Your website is the first impression that you give potential customers and clients. It’s a chance for you to tell your story and show what sets you apart from your competition. This will give you a chance to build trust with your audience, which can be invaluable in terms of repeat business.
A good website should be quick loading and clear. It should also have simple navigation, so that it’s easy to find what you’re looking for on the site. This is a great way to make sure that your website is effective and will keep you competitive in the market.
It’s also a good idea to create content that educates your customers about the industry that you’re in. This will help you to become an expert and provide more value for your customers. This can be especially useful for businesses that don’t have an extensive amount of experience, such as a graphic design company.
It offers competitive services
If you are looking for a safe, reliable and convenient way to play the latest esports games online, then Parimatch is the right choice. It is one of the top ranked gaming websites and boasts a number of features that make it stand out from the crowd.
To start with, the website offers an impressive array of esports games, from the popular Counter-Strike to Dota 2. You can also place bets on the likes of Overwatch, Call of Duty, and King of Glory. The site also has a mobile app that lets you bet on the go.
You can deposit and withdraw funds in a variety of ways, including using credit cards, e-wallets, and cash via bank transfer. In addition, the site features a snazzy mobile-friendly design and a number of unique promotions that can help you boost your winnings.
The site also has a few interesting features, including a live streaming feature that makes it easier than ever to watch a game in action. There is also a competition section that offers a variety of esports prizes.
In addition, the site has a "safer gambling" portal that can help you set up a variety of alerts to keep you on the straight and narrow. These include deposit limits, time alerts, and product restrictions.
Lastly, the site has a very cool Loyalty Program that allows players to redeem a variety of rewards such as free bets and even free spins on their favorite slots. The best part is that all you have to do to take advantage of these perks is register for an account on the site.
The Parimatch esports site is easy to navigate, and it has a large number of games that are sure to excite any gaming enthusiast. In addition, the site is packed with information about upcoming events and is available in multiple languages. The website also has a number of other features, including an esports calculator and an online chat function.
It offers a variety of games
If you want to sign up for a betting account with Pari Match, you will need to make sure you have all the necessary information. This includes your name, date of birth, and email address.
The registration process will take you about 10-15 minutes and can be done via the website or a mobile app. The latter is far more convenient and will allow you to access the site from your smartphone.
Once you have the information you need, you will be able to register and start placing bets on your chosen event. You can also use the cash-out function, which lets you withdraw your stake if the result of your bet is not favourable to you.
There are also a number of different payment methods you can choose from when signing up for your betting account. These include Mastercard, Visa, and e-wallets such as Skrill, Webmoney, Qiwi, and Yandex.
If you’re a beginner, you can get a free bet when you sign up for a new account. This is a great way to boost your bankroll and test out the site before committing any real money.
However, you should be aware of the terms and conditions associated with the bonus. These can change at any time and you will need to read them carefully before claiming the offer.
Aside from the welcome offer, there are a range of other bonuses and promotions available at Parimatch. These include a 150% bonus up to INR 30,000 and a 16x rollover on single bets.
The first deposit of INR 200 is eligible for the bonus, and it can be withdrawn once you meet the requirements for a rollover of 16 times the bonus amount on single bets. You can also claim the bonus without using a Pari Match promo code.
There is a wide range of sports wagering options at Parimatch, including football, basketball, rugby, hockey, cricket, and boxing among others. In addition, you can find live streams of most of the major events on the site.
The Parimatch esports website is easy to navigate and features an attractive design. It is divided into clearly defined sections and includes a list of all the games that are currently available for betting. It also provides a list of upcoming matches and allows you to see your bet slip on the right side of the page.
It offers a variety of payment options
Parimatch esports is an online gambling platform that offers betting on a variety of esports games. It accepts a variety of payment options including credit cards, e-wallets and cryptocurrencies. The site also has a customer support team that responds to questions quickly and effectively.
When signing up for a betting account, you will need to provide your name, email, date of birth, and contact information. You will also need to select your country and currency.
The registration process is simple and straightforward. All you need is to fill in the required fields and click on “Register”. After that, you will receive a confirmation email.
Many bettors prefer to use electronic wallets when depositing and withdrawing funds. This method has become a convenient replacement for a bank card. In addition, it provides a more secure method of depositing and withdrawing money.
If you’re a new user, you can get a bonus of up to 100% to your first deposit with the help of a promotional code. You can also take advantage of a loyalty program that will increase your bankroll and give you the opportunity to win free bets.
Another way to increase your account balance is by using a cashback bonus. This will allow you to reduce your losses by up to 20%. This offer is available to all users and is valid for a period of one week after the completion of the transaction.
There are a lot of bonuses and special offers that can be activated by using a promo code from Parimatch. These bonuses are designed to make the game more attractive and encourage players to stay with the bookmaker.
A Parimatch bonus code for a free bet can be used at the time of registration and verification. The bonus is automatically credited to your personal account once the verification process is complete.
In addition, the site also offers additional rewards for active participation in games and events. This can include free bets, a prize for the best player, and more.
The company is always prepared to surprise its customers with generous offers, and it’s not unusual for them to give gifts to their loyal members. This is especially true on the eve of holidays. | <urn:uuid:816922d7-0f1c-47d9-a1e1-569fdb6029f9> | CC-MAIN-2023-40 | https://bettingsiteonline.co.tz/registration-parimatch-2023 | 2023-09-28T17:35:30Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.957058 | 1,835 |
Wrapping up the last long weekend of the summer, The Taste returned to Paramount Pictures Studio backlot for a three-night culinary celebration of the city’s top toques and trend-setting global restaurant concepts. Hosted by the Los Angeles Times editorial staff, the backlot food crawl showcased the diverse epicurean culture from Thai to Ethiopian and Indian cuisine along with chefs from the award-winning outposts such as The Bazaar by Jose Andres who served Hamachi cones, Cal Mare Mediterranean cuisine rolled out saffron arancini and HomeState made their famous queso with brisket chili.
In addition to cooking demos, conversations, live music and interactive games, there were cocktails by top mixologists, wine tastings, and artisanal beer flowing on tap. The festive street vibe which drew sold-out crowds in its 10th year, ended harmoniously by also benefiting two local charities: The Collins College of Hospitality Management and L.A. Regional Food Bank.
Photos By Devin Berko | <urn:uuid:6d921165-3718-4c85-9bda-0b736a4fa2d6> | CC-MAIN-2023-40 | https://beverlyhillscourier.com/2019/09/06/the-taste-celebrates-a-decade-of-dining-on-the-paramount-backlot/ | 2023-09-28T18:03:11Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.932023 | 207 |
Two of the most common and basic procedures, yet most important, are dental cleanings and exams. These processes provide professional cleanings which prevent gum disease and maintain a great-looking smile.
During a cleaning and exam, our skilled dentists will:
- Clean plaque or tartar off your teeth, preventing decay or periodontitis
- Polish and floss your teeth
- Examine teeth for signs of diseases or damaging dental conditions
In these appointments, we may utilize dental x-rays to adequately evaluate your smile and make sure you receive the dental aid you need. To maintain good oral health, these dental cleanings and exams should be made to be regular recurring appointments to prevent and treat complications like cavities and gum disease as soon as possible.
Our team recommends that you schedule a routine cleaning and exam every six months. If during these visits we discover issues, we may request more frequent visits to ensure your smile stays healthy. In addition, if there is ever a dental emergency, we ask you not to wait until your regularly scheduled appointment, and contact us as soon as possible. To start scheduling your recurring appointments, we invite you to visit or call us today. We look forward to keeping your smile shining. | <urn:uuid:eb1d4af3-45b6-4f10-a7bf-baac2c527d3c> | CC-MAIN-2023-40 | https://beyonddentalhealth.com/services/general-family/dental-cleaning/ | 2023-09-28T17:27:52Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.950184 | 247 |
Just 8 months ago, Zara Jillings was still dressing up for basketball games – fighting for rebounds and directing the offense for Fordham university at the Atlantic 10 tournaments. Instead of digital people, she managed partnerships in pick’n’rolls or in a zone coverage. After the Coronavirus cut the NCAA season short, the junior point guard decided to pivot. She had a successful career, representing New Zealand at international tournaments, and appeared in all 100 of her university’s games in those 3 seasons.
However, that’s when her major in information technology became the point guard’s new starting point. Today, Zara works at as a partner account manager in Soul Machines. That’s a conversational AI company that creates “Digital Persons”, an advanced human-like conversational interfaces – and helped New Zealand handle the Coronavirus crisis in an admirable way. Now, in the Sweet-16 episode of Taking Turns, she got the court to tell her story.
• HOW DID YOU make the transition from basketball to CONVERSATIONal AI?
If you asked me a year ago, would I be here? I definitely wouldn’t have. I didn’t know much about conversational AI, and I was very focused on basketball and on studying. So I did do a Master in information technology, that was the start of what got me into this this area. Then, I found some people in Soul Machines. I was able to begin working with them, absolutely fell in love with company and the digital people, fell in love with what we’re doing, and it’s really just snowballed from there.
So I’ve been able to take a lot of different things in my stride. The basketball is very much the pathway that got me here. And now that I’m at Soul Machines – I’m just loving it and making the most of every minute.
• Can you see similarities between those two distant worlds? Any practices from basketball you were able to implement in Soul Machines?
At first glance, there’s probably isn’t anything similar. But when you think about it a little more and dive deeper, there’s stuff that just does make sense. So in basketball, as in any team sport and in any team business, being able to communicate is so important. Now, taking some of those skills across to the conversational AI and sort of knowing different ways that people talk and might listen, is really helpful. And in general, I’m lucky that my time management skills were pretty good. Because it was a busy lifestyle as basketballer and it’s still busy lifestyle now, but it definitely played me well.
• Why IS SOUL MACHINES concentrating on the aspect of Digital people?
In Soul Machines, we create astonishing digital people. And what’s really powerful about this, is that in an age where so many of our interactions are becoming mediated by technology or in a technology, or in a Covid world when you can’t really go and interact face-to-face with a lot of people, having a digital person allows you to humanize some of those interactions.
So from a brand standpoint, you could have a Brand ambassador that interacts with customers seamlessly across all channels. Whether it be mobile, online, installed by your kiosk. What’s unique about Soul Machines’ digital people is that you have an emotionally responsive interaction, something that can be really really engaging. As a result, you feel more connected, more human, more in touch with the brand. Hence, it’s perceived as more modern and more interesting, more effective.
All of those things make a digital person a really great way to go about some standard things that might be handled simply by chatbot, or by live agent. Here you’re having the best of both worlds; Obviously you can still pass on to a real human if that’s necessary in any instance.
💬 Previously on Taking Turns – Check out the whole playlist 💬
Maciej Maliszewski: “Chatbots can be the most important business channel”
How the Roo Chatbot is creating and reflecting a societal change
Rebecca Evanhoe: “Context is the most important thing for voice“
Emiel Langeberg: “Voice Tech can be also a research tool”
• from your experience, Are people more likely to chat with a human-like chatbot then with the a regular chatbot icon??
Definitely, we found that people definitely like the more human and interactive experience. Sometimes you can get a little annoyed if a chatbot ask the exact same thing all the times; That’s not to say that a digital person might not mis-hear you in some instances, or might not understand exactly how to reply. However, in most cases by having an interaction with a digital person, people do feel like it’s more natural rather than talking to just a chatbot. It has its benefits across the board. Personally, I know about digital people, I love going talking to Soul Machines’ digital people. I love seeing what they’re doing in the wild. So, it’s really amazing.
• we’re all jealous of the way that your PM, Jacinda Ardern, handled the Corona crisis. you created a digital person called Bella to help fight Covid. Can you talk about its impact?
Bella was a digital person that we created right back at the start of the pandemic, in April. There was so much misinformation, both across the globe and within New Zealand. And people just didn’t understand what the different Coronavirus measures meet. So in New Zealand, we had an alert level system that went from 1-4. And so, what Bella was capable of doing is telling people: This is the alert level we’re at; This is what it means. If someone asks, ‘Hey, can I get a haircut?’, Bella would know the answer and be able to share that with you.
And again, all of this was done with sort of her past personality mixed in. So rather than saying, ‘No, you can’t’, or ‘Yes, you can’ to the haircut question, she’d say something like – She’d say something like, ‘uh, that’s what everyone’s been asking me. I don’t have to worry about it because I hear doesn’t grow, but you can get a haircut starting next week’. So it was really fun.
In addition, focusing on that Coronavirus aspect, people could ask questions. They could ask about symptoms and treatment, where to go for help and what number to call. We found that that was really useful and really utilized by a lot of people. The Corona era made so many people feel lonely or isolated. And people had businesses that were really struggling. So we made Bella more of a holistic Kiwi digital Helper and digital friend.
CoCo & Co Content reCommendations
- How AI is making an impact on incumbent industries?
- Soul Machines’ Kent Morita: When should a chatbot use humor?
- How can Conversational AI help in the fight against the Coronavirus?
- Check out our conversational AI glossary
She had information and support on mental health tips and resources. There’s the really pioneering expressing kindness challenge. You can come back within three days, talk to Bella and get a different challenge to go. You could learn about expressing a little bit more kindness, appreciation, gratitude. And how all of that can help you both physically and mentally. Then, from business standpoint, we interviewed a lot of Business Leaders throughout New Zealand. We got their advice and support for – ‘What can I do right now? It feels like my business is just going down the drain’.
So people had a lot of really great engagement with Bella across the board. Definitely, we were proud to put her forward as sort of – Soul Machines is here to help. At this time, we want to do what we can to make a difference.
• What can you tell people who are deterred by the blurring boundaries between regular people and digital people – the moral Panic of “bots will replace us”?
People will always be skeptical about new technologies, and digital people are still very much at the frontier of what’s happening. And I think five years from now, this will be more commonplace; Since we were founded at 2016, five years ago these sort of things barely existed, especially at Soul Machines’ level.
At the moment, people have those concerns and might think it’s a little bit freaky or scary. However, we’ve actually found that talking to a digital person, after a minute to two minutes, those sort of perceptions really fade away. People find the experience again to be engaging and interesting – rather than being weird, as prior to speaking to what you might have thought.
Then, on general level, the fear about automation or robots – ‘Oh, they’re coming for our jobs and being able to think for themselves!’ That is all still – as far as I understand – definitely further away. Right now we’re in this space of more ‘narrow AI’. Even within conversational AI, there is some conversation abilities that can generate what they’re going to say. But a Soul Machines digital person is what we call like a truth teller; They’ll say exactly what that company or brand wants as their messaging. So they’re not going to come out in and talk about something else or try and take over.
Although it’s valid for people to have those fears, from my perspective, it’s not something to be too worried about. I want everyone to have really great experiences with digital people and to realize how powerful it can be.
• If somebody wants to rebound, go out on a transition and start a career at conversational AI like you – what tip can you give Them?
It’s a great question and, I do love the basketball analogy… for me, this came out of nowhere. And I’m so glad I found it. So if people are seeing this, I’m sure they’re already a little bit within that conversational AI space. The viewers know CoCoHub, now hopefully know Soul Machines and being interested in that. There’s just such a wealth of information available online, and so many different skills that now you can go and learn.
So I know that every day while I’m working, I’m still looking at other stuff. I’m still learning other stuff. And my learning has gone just through the roof. That’s really exciting for me. For everyone, everywhere, if you’re interested in the space, just throw yourself into it. Places like CoCoHub are doing amazing things and making it so much easier to be involved in conversational AI. Then come talk to Soul Machines and see what we’re doing. Then you can see how everything ties together to create those really powerful experiences.
• if I tOLD you that there is one NBA player who is a digital person and nobody knows it – Who would you bet on?
Hands down, LeBron James. That man, he’s not human. He has to be digital. He’s just crazy too unreal, too impressive, too talented. So maybe it would make me feel better if he was a digital person, because – yeah, as a real human person he is pretty phenomenal.
I would go with that Kawhi Leonard, you probably heard his laugh – it sounds robotic, it sounds like a glitch.
Yeah. He’s a bit of a robot. That’s actually that’s a sneaky one. Alright, Kawhi Leonard is definitely my #2.
Next week, we’ll have episode 6 of Coming To Terms with AI! In the meanwhile – subscribe to our YouTube channel | Join our Discord community | Sign up for our newsletter | Follow us on Facebook, LinkedIn, Instagram or Twitter | <urn:uuid:b63166fd-fd69-495f-829f-eb3565aeb004> | CC-MAIN-2023-40 | https://beyondvirtual.ai/transition-game-how-zara-jillings-pivoted-from-hoops-to-digital-people/ | 2023-09-28T16:54:26Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.963635 | 2,586 |
Isaiah Chapter 35
Verses 35:1-10: The prophet Isaiah now turns to a message of hope for the future. After the great destruction of the Tribulation period will come the blessing of the millennial age when the desert “shall rejoice, and blossom as the rose.”
In the Messiah’s kingdom, all spiritual evil and physical catastrophe will be reversed and the land and people will be blessed. “Carmel and Sharon,” the normally fertile regions of Israel, though devastated by the Battle of Armageddon, will once again be fertile and productive.
One day they will blossom more beautifully than the cedar forests of “Lebanon.” The “highway” is contrasted to the desolate desert and its endless maze of shifting sands. It will be the “way of holiness” and will be reserved for the “ransomed” and “redeemed” of the Tribulation period who will enter the millennial kingdom.
Verses 1-4: In contrast to luxuriant Edom that is to become as desert (34:1-17), during Messiah’s reign on earth the whole world is to become like a flourishing garden and this will offer encouragement to the weak.
Isaiah 35:1 “The wilderness and the solitary place shall be glad for them; and the desert shall rejoice, and blossom as the rose.”
(In chapter 34), we read about the judgment of God on a people who were alienated from God. In this chapter, we read of the blessings of God on those who choose to follow Him.
Dramatic changes in the land are to come during the Messianic age (see Isaiah 30:23-25; 32:15-20).
The same desert that had been desolate for the evil ones, blossoms for the beloved of God. Just after the wrath of God is over, the Christians come back to the earth to reign with Jesus.
Isaiah 35:2 “It shall blossom abundantly, and rejoice even with joy and singing: the glory of Lebanon shall be given unto it, the excellency of Carmel and Sharon, they shall see the glory of the LORD, [and] the excellency of our God.”
“Lebanon … Carmel and Sharon”: Areas near the sea noted for their agricultural fertility. “They will see”: Israel is to recognize the earth’s newfound fruitfulness as coming from the Lord and attribute to Him the appropriate credit.
The church of the Lord Jesus Christ has been delivered from the troubles of the world during the wrath of God on the earth. We see them now, dancing and singing, rejoicing in the Lord. The glory of the LORD will be upon the earth in the presence of God’s people at this time.
Revelation 20:6 “Blessed and holy [is] he that hath part in the first resurrection: on such the second death hath no power, but they shall be priests of God and of Christ, and shall reign with him a thousand years.”
During this reign of Jesus as King, the devil will be chained. There will be nothing harmful, or negative at all. The weather will be perfect. The crops will grow abundantly. The Light of the world will be present. All of nature will be operating in cooperation with Jesus our King. Even the temperature will be perfect.
This is speaking of the 1,000 year Sabbath of rest for the Christian that is spoken of as the Millennium reign of Jesus Christ upon the earth. The six 1,000 year days have ended and the one 1,000 year day of Sabbath is here.
Isaiah 35:3 “Strengthen ye the weak hands, and confirm the feeble knees.”
“Weak … feeble”: The future change in Israel’s international role is to serve to encourage the discouraged among the people. The writer of Hebrews gave an additional application of this verse to strengthen endurance among Christians suffering persecution for their faith (Heb. 12:12).
Isaiah encourages the people he is giving this prophecy to. He says strengthen each other in the knowledge this great day is coming. Build each other up in the most holy faith.
Romans 15:1 “We then that are strong ought to bear the infirmities of the weak, and not to please ourselves.”
Isaiah 35:4 “Say to them [that are] of a fearful heart, Be strong, fear not: behold, your God will come [with] vengeance, [even] God [with] a recompence; he will come and save you.”
The vengeance of God (34:8), is to furnish the means to redeem His long-oppressed people of Israel.
Those who are strong must help those who are of a fearful heart. Be strong in the Lord and in the power of His might. Encourage those who are weary and fearful. To be fearful means the faith is not as strong as it should be. Build others up in the most holy faith.
Some become fearful, because they have given up on the Lord coming back to save them. The best way to encourage them is with Scripture.
Isaiah 35:5 “Then the eyes of the blind shall be opened, and the ears of the deaf shall be unstopped.”
“Eyes … opened … ears … unstopped”: This is to reverse the spiritual condition of the immediate objects of Isaiah’s ministry (see 29:18; 32:3).
This prophecy was fulfilled in part, when Jesus ministered on the earth for 3-1/2 years and did miracles. This has a larger fulfillment, in the fact that all will hear and understand during His reign on this earth as King. In the presence of our King, all will hear and all will see.
Unfortunately, from the children born to those who go into the Millennium, many will rebel and not follow Christ even in such a perfect environment.
Verses 6-7: Water was and is a precious commodity in Israel (41:18). In the Millennium, there will be no scarcity.
Isaiah 35:6 “Then shall the lame [man] leap as a hart, and the tongue of the dumb sing: for in the wilderness shall waters break out, and streams in the desert.”
God’s restoration in the millennial age is to include physical restoration to the afflicted. Jesus’ first coming gave a foretaste of that future day (Matt. 11:15; 12:22; Mark 7:37; Luke 7:21; Acts 3:8).
The devil is the author of blindness, deafness, and lameness. Since he will be chained, there will be no one who cannot walk, or talk, or see, or hear. The hearing and seeing are not only in the physical, but in the spiritual, as well.
No one will have to teach of Jesus then, because all will know Him.
Isaiah 35:7 “And the parched ground shall become a pool, and the thirsty land springs of water: in the habitation of dragons, where each lay, [shall be] grass with reeds and rushes.”
The rocky crags normally inhabited by jackals (34:13), are to become splashy meadows.
There is not just a total restoration to man in that day, but to all of nature as well. The earth will be like the Garden of Eden.
Where the land had been parched in the time of the wrath of God, now the rivers flow. There will be natural springs rising out of the ground that will bring clear, pure water. Life will spring forth in the desert areas. The grass and plants will flourish in the desert.
Isaiah 35:8 “And a highway shall be there, and a way, and it shall be called The way of holiness; the unclean shall not pass over it; but it [shall be] for those: the wayfaring men, though fools, shall not err [therein].”
This refers to the way leading the redeemed back to Jerusalem, the throne of Messiah, literally and spiritually. Christ Himself is to be the leader on that way (called in 40:3), the “way for the Lord.”
The straight and narrow path will still be there, but it will be no problem to stay in the way. The temptation to sin will not be coming from every direction then. This road, provided by God for His followers, will be well marked. It will be holy. All who walk on this road are headed for an eternity in heaven with God.
The Light of Jesus will light up the path that we are to walk. He is the Way. The world may think you to be a fool, but you will be wise unto salvation. This path is not for the worldly. This is the path of the righteous.
Isaiah 35:9 “No lion shall be there, nor [any] ravenous beast shall go up thereon, it shall not be found there; but the redeemed shall walk [there]:”
No ferocious beasts are to threaten the safety of those traveling the Highway of Holiness. “The redeemed”: Mentioned only rarely in chapters 1-39 (1:27; 29:22), whose theme is judgment; terms for redemption occur frequently in chapters 40-66.
The lion will be harmless to man at this time.
Isaiah 11:6-7 “The wolf also shall dwell with the lamb, and the leopard shall lie down with the kid; and the calf and the young lion and the fatling together; and a little child shall lead them.” “And the cow and the bear shall feed; their young ones shall lie down together: and the lion shall eat straw like the ox.”
Just as Moses led the children of Israel to their promised land, Jesus will lead those He has redeemed to their promised land (heaven).
Revelation 5:9 “And they sung a new song, saying, Thou art worthy to take the book, and to open the seals thereof: for thou wast slain, and hast redeemed us to God by thy blood out of every kindred, and tongue, and people, and nation;”
Isaiah 35:10 “And the ransomed of the LORD shall return, and come to Zion with songs and everlasting joy upon their heads: they shall obtain joy and gladness, and sorrow and sighing shall flee away.”
“The ransomed … flee away” (see 51:11), where the words occur again. Gladness is to replace sadness across the board in the day of Israel’s restoration.
Zion, in this Scripture, could be that heavenly Zion. Ransomed means we have been purchased back. Jesus purchased (ransomed) us with His precious blood at Calvary. We had been held hostage by the old devil. Jesus paid the ultimate price to ransom us.
The song we sing, only the redeemed can sing. The joy to be set free is overwhelming. This joy lasts forever. Once we are with Him, joy and gladness are ours to keep. He will wipe all tears away from our eyes. There will be no more sorrow.
To be with Jesus is the greatest joy a Christian can experience. The greatest part of all this is, we will never be separated from Him again. PRAISE THE LORD!
Isaiah Chapter 35 Questions
- What do we read about in chapter 35?
- The wrath of God is ______.
- Where will the Christians be at this time?
- What is the church doing to rejoice?
- Where will the devil be at this time?
- Tell a few things that show how perfect it will be on the earth at this time.
- What is the 1,000 year reign of Jesus called?
- What are we to say to those with a fearful heart?
- How is the best way to encourage the fearful?
- What miracles are spoken of in verse 5?
- The lame man will leap as a ______.
- The tongue of the dumb will ______.
- Besides the miracles in the physical that take place, what else happens?
- What is the highway called in verse 8?
- Why will it be so easy to stay on this path?
- What lights the way?
- Where does this path lead?
- The ___________ of the Lord shall return to Zion.
- What were we ransomed with?
- What is the greatest joy a Christian can experience?
Other Books of the Bible (This takes you to our new 66 books of the bible menu)
Email Us : firstname.lastname@example.org | <urn:uuid:dc8604da-6e63-42c7-905a-995820599c32> | CC-MAIN-2023-40 | https://bible-studys.org/isaiah-chapter-35/ | 2023-09-28T18:23:26Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.939162 | 2,702 |
At BIG we take privacy very seriously and we are committed to protecting and respecting your rights.
This document explains when and how we collect personal information about people who visit our website and/or use our services through website and on-line servers and are exposed to advertising we provide. It also explains how we use such personal information, the conditions under which we may disclose it to others and how we intend to keep it secure.
At all times we adhere to the relevant privacy rules in each territory and in within the European Union we follow the rules of the General Data Protection Regulation introduced in May 2018 addressing the transfer of personal data outside the EU. When we collect personal data via the Website such as email address and other contact details, we will obtain your consent. When prospecting for new Customers and Partners, we will collect personal data through legitimate sources and delete such information if no longer required.
Who we are
We are BIG – providers of a creative marketplace platform which also allows for the production of Deal IDs for quality publishers and audiences. We are an Australian entity and our full name is Big Mobile Group Pty Ltd (Australian Business Number: 15119902966)
How do we collect information from you?
We process very limited information about you
Such Personal Information is collected in the following ways:
- On our website and servers, when you visit and browse through it and/or use any of the services we provide
- On behalf of our clients: We collect Personal Information when you use any of our providers products or services which use Ads within them. What this means is that when you for instance use an App or visit a web page from a mobile device that shows Ads, chances are that such advertisement impressions have been “purchased” by companies using our software as a service platform in order to serve you such Ads. Our advertisement serving software collects Personal Information to the extent and in the way explained in this policy
- For those who sign up to our platform “Buddy” we collect some personal information – name, email, company and mobile phone number
What type of information is collected from you?
The Personal Information we collect through our website/servers and/or on behalf of our clients include cookies and on-line identifiers from the mobile device used to run the App or browse the web pages in which the Ad impression was served and might include as well the IP address being used at the time the Ad was served and other ancillary information such as: the size of the ad space, the operating system and version running in your mobile device, the category of the app or website where it was served, or the approximate location of the device.
‘Cookies’ are small text files containing pieces of information (often including a unique identifier), sent to your computer and stored on your hard drive to allow a website to recognise you each time you visit. They collect statistical data about your browsing actions and patterns and do not generally identify you as an individual.
Mobile devices identifiers have been likened to cookies.
Please note that while these cookies and device identifiers are regarded as Personal Information and while we process and protect them as such, they do not specifically and automatically identify you as an individual. While it would be extremely difficult for us or for any third Party to know about your specific identity using this information, at any time you might choose to: erase or remove your browser cookies as well as reset the on-line identifier of your mobile devices rendering all and any personal data linked to such devices obsolete.
How do we use your Personal Information?
Website and server cookies are used internally to measure how the different sections from our website work, track your browsing through it and also in order to find out where is the traffic coming from at any moment in time.
These cookies are used to identify you within the platform and in order to provide you with our relevant services. The information collected may include IP address, cookie information, browser version, operating system type and version, mobile network information, device settings and software data.
We use this information to:
- To target their advertisement campaigns, for example within the correct territory through IP targeting.
- To generate user segments (what we call “audiences”) based your previous interactions with any advertising campaigns;
- To understand whether you are part of a certain user segments;
- To know whether or not you have engaged with an advert.
All this information maybe used to create a profile to target you with the relevant advertising.
We will hold this information on our systems for as long as is necessary for the relevant activity (we have set a general maximum limit of six (6) months).
DURING THE AD BUYING PROCESS WE DO NOT COLLECT INFORMATION SUCH AS NAME, AGE, PHYSICAL ADDRESS, EMAIL ADDRESS OR OTHER PERSONAL INFORMATION.
We do share information with certain partners during the moment we purchase or attempt to purchase the advertising slot. For example, we work with some data providers and by looking at the ad slot and device information which is provided at that moment we cross check with the data provider to see if there is a match and then serve the relevant advertising.
When always ensure that any third part data providers conform to same strict privacy rules that we do to keep your information secure and not to use it for any other purposes.
You may refuse or accept cookies from websites at any time by choosing the appropriate settings on your browser. Most browsers automatically accept cookies, but you can usually modify your browser setting to decline cookies if you prefer. Please we aware that should you choose to decline all cookies, you may not be able to sign in or use other features of our website that depend on cookies.
Information about the procedure to follow in order to enable or disable Cookies can be found at:
- Chrome: https://support.google.com/chrome/answer/95647?hl=en
- Safari: https://support.apple.com/kb/ph21411?locale=en_US & https://support.apple.com/en-us/HT201265
- Firefox: https://support.mozilla.org/en-US/kb/delete-cookies-remove-info-websites-stored
- Microsoft Explorer: https://support.microsoft.com/en-us/help/17442/windows-internet-explorer-delete-manage-cookies
For more information about other commonly used browsers, please refer to http://www.allaboutcookies.org/manage-cookies/.
To opt-out of participating in Google Analytics data follow the instructions: https://tools.google.com/dlpage/gaoptout.
Creative Marketplace Platform – Buddy
We collect information about our customers to ensure that we can accurately provide the correct services for them. If you agree to use Buddy then you are signing up to the Buddy T&Cs (put link to Buddy T&Cs here). By providing the agency name and seat identity for your chosen demand Side Platform we can push through the correct Deal ID for your campaign. If you decide to stop using our platform then we will purge your account and all data within six months.
Opting-out of interest based advertising
You can opt out by changing the settings on your Android or iOS phone or tablet.
Your iOS or Android mobile device provides a “Limit Ad Tracking” or “Opt out of interest-based advertising” setting. When you have opted out using this setting on a device, we will not allow our clients to use personal information collected from that device for any targeting purposes, nor to create any user segments.
You can find the setting for your mobile device by following the directions below:
- iOS Device iOS 7 or Higher: Go to your Settings > Select Privacy > Select Advertising > Enable the “Limit Ad Tracking” setting iOS 6 Go to your Settings >Select General > Select About > Select Advertising > Enable the “Limit Ads Tracking” setting More information about the iOS setting can be found here. Android Device.
- Android devices with OS 2.2 and up and Google Play Services version 4.0 and up: Open your Google Settings app > Ads > Enable “Opt out of interest-based advertising” If you’ve turned on Limit Ad Tracking on your iOS device or the Opt out of interest-based ads on your Android device, you can restore interest-based ads by turning the settings off.
When you opt out this does not block ads but simply means that the ads you now see are less relevant because there is no information to understand the end user.
You can opt-out of interest based advertising coming ONLY from our clients by providing us your advertising identifier (IDFA if you have an iPhone or GAID if you have an Android phonePlease email us at email@example.com if you wish to opt out with your advertising identifier or mobile device universally unique identifier (UUID).
Security to protect the loss, misuse or alteration of your information
We take this matter seriously and we’re continuously evolving our platform to make sure data integrity and data security are always a priority. Our platform and servers use encryption techniques for storage and transmission of data.
We are concerned to protect the privacy of children. If you are aged 16 or under‚ please get your parent/guardian’s permission beforehand whenever you provide us with personal information.
Information stored outside of Europe
We are an Australian company but operate within the privacy rules of the European Union and the GDPR rules – some of our servers are located in a country outside of the European Union where there are different data protection laws. By providing us with any Personal Information, you’re agreeing to this transfer, storing or processing. If we transfer your information outside of the EU in this way, we will take steps to ensure that appropriate security measures are taken with the aim of ensuring that your privacy rights continue to be protected as outlined in this document.
If you use our services while you are outside the EU, your information may be transferred outside the EU in order to provide you with those services.
Privacy Policies of our supply partners for your reference
- Airtory (https://www.airtory.com/privacy-policy)
- Google (https://policies.google.com/technologies/partner-sites)
- Inmobi (https://www.inmobi.com/privacy-policy/)
- Near (https://near.co/privacy/)
- Nexd (https://www.nexd.com/privacy-policy/)
- Rubicon / Magnite (link to: https://rubiconproject.com/rubicon-project-advertising-technology-privacy-policy/)
- The Trade Desk (https://www.thetradedesk.com/general/privacy)
- Xandr (https://www.xandr.com/privacy/platform-privacy-policy/)
IMPORTANT: If you do not agree with this transfer of Personal Information outside of Europe email: firstname.lastname@example.org | <urn:uuid:a485e6a8-354e-4557-8ea8-27a23f45b4ee> | CC-MAIN-2023-40 | https://bigads.co/privacy-policy/ | 2023-09-28T17:01:59Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.902229 | 2,383 |
We're Bringing the Pain (Glow-in-the-Dark Exclusive)!
Easily the most Iconic Antagonist in Naruto Fandom is none other than Pain!
Utilizing the Corpse of his deceased best friend, the life support bound Nagato goes on to coordinate and wreak havoc among the world of Ninja using Yahiko as his Avatar to bring Pain to life!
This Pain is arguably the most powerful- able to control the physical presence of nearly anything in existence by pushing and pulling them at will.
While that may seem rather lackluster ability, Pain makes his grand entrance to the Hidden Leaf Village by completely leveling the quaint Village using his ability, causing mass chaos and confusion.
The varying abilities of the different Pains cause widespread death and destruction.
He even takes out the fan favorite Kakashi for a brief spell by using his signature "Almighty Push" to finish him using a nail- talk about gruesome!
We're offering up a sweet Glow exclusive pop featuring Yahiko Pain using his Almighty Push technique in order to destroy Konohagukure.
The attention to detail on this Funko POP! is insane. From the several control rod piercings in his face to the Akatsuki ring on his fingers, we get a Pain that is true to his source material.
Not only Is this Pain highly detailed, He's positioned on a stand levitating as when he shows himself ready to bring his namesake.
His glow is nothing to scoff at either! Yahiko's hair has a bright orange glow, and more subtly, but also more importantly, his Rinnegan eyes and Akatsuki clouds glow as well!
Be sure to get yours asap here at BT Collectibles! We'll be giving these Pain's the "Almighty Push" to your doorstep quickly as they're In Stock now!! | <urn:uuid:b9511584-e443-4881-b20e-eadf5123b61a> | CC-MAIN-2023-40 | https://bigtoescollectibles.com/blogs/news/were-bringing-the-pain-glow-in-the-dark-exclusive | 2023-09-28T17:49:59Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.959271 | 389 |
Not a member? Join Us
Forgot your password?
Your cart is currently empty.
Hurry, low quantity!Hurry! – Only 98 left in stock.
Introducing the ultimate cycling accessory that will take your rides to the next level! Our Bicycle Saddle with Tail Light is a game changer for anyone who loves to cycle in style, comfort, and safety.
First, let's talk about comfort. Our saddle is designed with a premium quality foam material that provides superior cushioning, ensuring you enjoy a comfortable ride, even on bumpy roads. The ergonomic design of the saddle helps to distribute your weight evenly, reducing pressure on your sensitive areas, and allowing you to cycle for longer without experiencing any discomfort or pain.
Now let's talk about safety. The tail light that comes with our saddle is an added bonus that will keep you safe during your rides, especially when cycling at night. The bright red LED light has multiple modes that can be easily switched depending on the lighting conditions. The light is easily detachable, making it convenient to charge, and attach back to the saddle. Efficient lighting just like Hard shell Bicycle Saddle can be used as Camping Accessories.
But that's not all. Our Bicycle Saddle with Tail Light is not just about comfort and safety, it's also about style. The sleek and modern design of the saddle is sure to turn heads and make a statement. You'll love the way it looks on your bike and how it adds to your overall cycling experience.
In conclusion, our Bicycle Saddle with Tail Light is a must-have accessory for any cycling enthusiast who values comfort, safety, and style. Get yours today and take your cycling experience to the next level!
Each bike has a bicycle seat when purchased. In order to ensure a comfortable and, most importantly, safe ride, you need to take care that the bike has the right lighting. The rear dimensions of the bike are indicated by the red rear bike light. You can buy a separate rear bicycle light. But we offer you 2 in 1, Bicycle Saddle with Tail Light. Our seats are comfortable, and the built-in lamp will always be with you and will not be lost from shaking on a bad road. Among other accessories for bicycles, you can order an Aluminum pump with a pressure gauge. | <urn:uuid:6665cd7d-e421-4ebc-9ce2-7c49d32dfa90> | CC-MAIN-2023-40 | https://bike-west.com/products/bicycle-saddle-tail-light | 2023-09-28T17:11:06Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.946899 | 474 |
It’s tough to think about on a beautiful summer day, but remember how freezing we were last winter? Well, don’t worry: Philadelphia could see a warmer-than-average winter this year, thanks to an El Niño that’s forming in the Pacific.
What’s that? Oh. It’s a complicated system that involves trade winds and the temperature of the Pacific Ocean, and it can throw off weather patterns across the globe in a variety of ways — including making the northeastern and mid-Atlantic states susceptible to warmer, wetter winters.
And meteorologists with the National Weather Service have early models that show there is a 90 percent chance that an El Niño will continue through the Northern Hemisphere during the winter, and around an 80 percent chance it will last into early spring of next year.
Mitchell Gaines, a NWS meteorologist based in Mt. Holly, NJ, said there’s still a lot of uncertainty for what the winter could look like (literally, when we called, the person who answered said “It’s July”). But if a strong El Niño does form, it could cause warmer winter temperatures into our region. It’d also cause warmer weather in the Great Lakes and Ohio Valley, cooler temperatures in the southeastern states and potential storminess in the southern states.
Here’s the short version of how El Niño works:
Under normal conditions, trade winds travel from east to west in the Pacific, bringing along ocean water heated by the sun on the surface and warmed neutrally. But under El Niño conditions, the trade winds become disrupted and the cold ocean water near South America isn’t rising up as usual. The waters start to warm.
As more water warms up the Pacific, the more the trade winds get frisky. Precipitation follows the warm water, and once sea surface temps in the Pacific rise more than 0.5 degrees Celsius over what they normally are during a three-month span, then meteorologists will declare an El Niño.
All of this changes how jet streams flow, and this is the effect is has on the world:
But other factors could come into play in our area, Gaines said. For instance, this year Philadelphia was in an avenue of cold air traveling south from Canada and the North Pole — remember the Polar Vortex? — which caused frigid temperatures in February and one of the coldest eight-week stretches on record. That *could* happen again this winter.
Theoretically, a strong El Niño would override that and still cause warmer air around here. But that’s if, and only if, the El Niño develops like meteorologists think it will. History shows that doesn’t always happen.
Experts predicted a strong El Niño last year around this time, would that they said would have been similar to one in 1997-98 that totally threw off weather patterns around the world. It can cause crazy flooding in South America, but can also help send needed rain to areas in drought.
But last year’s El Niño never came like meteorologists expected. A weak El Niño did form in the Pacific and surface temperatures rose, but it didn’t have the dramatic worldwide effects some expected. Models this year show one much stronger seems to be forming.
Moral of the story? There’s still a lot we don’t know about these types of weather patterns.
“It’s still July, so we have a lot of uncertainty for the winter,” Gaines said. “It does look like it will be a pretty strong El Niño. But there will also be a lot of smaller keys to the picture out here.” | <urn:uuid:bcfdd20e-459d-4c03-ad4d-f69a6011634e> | CC-MAIN-2023-40 | https://billypenn.com/2015/07/10/lets-talk-about-winter-experts-say-el-nino-could-mean-a-warmer-than-average-cold-season/ | 2023-09-28T18:55:46Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.943993 | 770 |
The stretch of South Broad that runs between Oregon and Washington is officially known as the “Avenue of the States,” and flags from all 50 U.S. states hang from lampposts along the strip. More interesting than those banners (which are sometimes there and sometimes not) are the antique lettered marquees and neon signs that adorn several of the street’s historic buildings.
Here’s a photo tour of nine of the most iconic, with a brief background about the shops they call out.
Philip’s Restaurant (1145 S. Broad St.)
In 1940, Philip Muzi opened an Italian restaurant, but, because the U.S. was at war with Italy at the time, chose to brand it with his first name instead of his last. One of the first establishments to offer air conditioning (which is noted on the sign), the spot was busy — according to a Hidden City interview with his daughter-in-law Phyllis, there were lines out the door each weekend night. Open through the late 1990s, the restaurant ceased service around the turn of the century, but the interior is apparently still intact (perhaps more so than the sign outside), filled with chairs and tables and lots of antiques and curios collected over the years by Philip Jr.
Meglio Furs (1300 S. Broad St.)
The building that houses Salvatore Meglio Furs entered the Philadelphia tax register back in 1957, and the neon sign that spotlights it appears to date from a similar era. The mannequins that still haunt the window of the now-shuttered shop appear to harken from a more recent time, however — probably the 1980s, if you judge from the style of a poster also propped up in the front of the curtained veneer.
Bambi Cleaners (2439 S. Broad St.)
How did Tom Pitucci get away with using Bambi’s likeness to advertise his dry cleaning business without raising the ire of Disney? Maybe because in the 1950s, when he founded the business, commercial copyright was less of an issue. Though Pitucci died in 1987, the business was sold and is still operating, with the adorable fawn still welcoming all who pass through its doors.
Dolphin Tavern (1539 S. Broad St.)
For years a scuzzy nudie bar, the Dolphin Tavern shut down in 2012. Half a year later, in March 2013, developer-restaurateur Avram Hornik reopened the doors, having left much of the character of the dive bar intact, but upgrading things like the beer selection, entertainment (music, not strippers) and the gorgeous neon sign that arcs across the facade.
Philadelphia Gas Works (1601 S. Broad St.)
In 1941, when the building holding PGW’s South Philly office was built, the energy company had already been in business for 95 years. However, that year marked the beginning of city ownership of the operations, and with the municipal takeover came several new office locations. Modernizations have swept through much of the organization (check out the snazzy new website), but the sign on South Broad remains the same.
Bell Telephone (2000 S. Broad St.)
Presiding over the giant intersection where Passyunk meets Broad and McKean is a gorgeously solid masonry structure built in 1962 for the Bell Telephone Company of Pennsylvania, which had just spent 50 years gobbling up other telcos on the way to becoming part of AT&T’s nationwide monopoly. After being broken apart by a 1984 mandate, the company became part of what is now AT&T’s biggest cellphone competitor: Verizon, whose logo is rather rudely slapped in front of the original stone-carved sign.
Lerro’s (2434 S. Broad St.)
From the time he was 1 year old to his death in 2008 at age 93, Pasquale Lerro spent nearly all his time at the confectionery shop his Italian immigrant father opened in 1916. The shop is now run by his son, John Lerro, and his grandson, John Pasquale. The family hasn’t changed the sign out front, nor have they changed their recipes, eschewing preservatives and artificial flavors (even though it meant they were shut out of a potentially lucrative contract with Wawa, per Hidden City).
Carto Funeral Home (2212 S. Broad St.)
There’s no definitive answer to why there are so many funeral homes on South Broad, but there’s no missing the phenomenon — they lace the sidewalk there with bittersweet reminders of life’s fragility. One of the more notable facades boasts white brick covered with black script lettering, announcing the location of Nunzio Carto Jr.’s coffin enterprise. What other businesses he’s involved in, it is not certain, but his granddaughter Natalie Guercio was a recent star of reality show ‘Mob Wives.’
Boot & Saddle (1131 S. Broad St.)
Philly architecture high priestess Inga Saffron recently devoted an Inquirer Good Eye column to the intricately shaped relic that has adorned this tavern since the 1950s. When Avram Hornik (see Dolphin Tavern) decided to revamp it into a more modern drinkery and live music spot, a condition of his takeover was a restoration of the neon-clad boot. Though it took nearly two years, that re-lighting finally got going in early June. As of last week, however, the sign still hadn’t been reinstalled — Boot & Saddle management responded to inquiries about its status with a firm “No comment.” | <urn:uuid:0976a7df-612c-4f3d-9d6b-88974c7397f3> | CC-MAIN-2023-40 | https://billypenn.com/2015/07/26/bambi-dolphin-boot-saddle-south-broad-streets-9-most-iconic-shop-signs/ | 2023-09-28T17:06:43Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.968597 | 1,192 |
We welcome you to our webpage Biseresultpk.com. Here we will provide all details about FBISE Federal Board Islamabad result of 10th Class 2023. All the candidates who were appeared in the FBISE 10th class exams can check the online Result method on this page.
Federal board matric result 2023
BISE Federal Board Islamabad 10th class, SSC, Matric part 2 annual result will be announced on Monday 18th July 2023 AT 02:00 PM. FBISE result 2023 declaration date announced.
If you are a 10th class student of Federal board, you must keep on visiting this page to get yours and your friends results online for free. As, the exams 2023 are conducted according to date sheets and exams schedule provided by the FBISE to its affiliated institutes. The 10th class result 2023 Federal board comes after about 40 day of exams.
|Class||10th Class ssc|
|Board||FBISE Fedral Board|
|Exam Type||1st Annual|
|Result Date||18th July 2023|
|Passing Marks||40% In Each Subject|
|Result Checking Availability||by name, SMS code, Roll number, and Gazette.|
We have shared the way that how you can get your FBISE result 2023 10th class on your mobile. You can check the federal board result home page here on Biseresultpk.cpm. Here we shared class 10th result 2023 Islamabad board roll number wise. Share this page with your friends to get them their results online. Wish you best of luck for your results.
How can I check my 10th result by SMS Federal Board Islamabad?
You can check your 10th result 2023 Federal Board Islamabad by SMS on you cell phone. Just send FB space your roll no. to 5050 and you will get your Federal Islamabad 10th result on your mobile phone.
How can I check my Federal Board Islamabad result by name?
You can check your Federal Board Islamabad 2023 by name from the gazette provided by board or visit our page on result day.
- Open fbise.edu.pk official website or below.
- Select the option “SSC Part-2”
- Select “Results” from the drop-down menu.
- Choose an exam type, annual.
- Enter your Roll Number in the given section.
- Check your results after you have submitted them.
How do I get my old 10th result of Federal Board Islamabad?
Enter your roll number and select your class of Federal Board Islamabad, click on search to find out your previous or old result of 10th Federal Board Islamabad.
How can I check my FBISE 10th Online?
You can check your 10th Federal Board Islamabad www.edu.pk and www.bise.edu.pk result 2023 here online on biseresultpk.com. | <urn:uuid:84260b7a-b1f9-4285-8e2c-8c4b0df42fa1> | CC-MAIN-2023-40 | https://biseresultpk.com/federal-board-matric-result-2023/ | 2023-09-28T16:44:02Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.872306 | 630 |
Bespoke loose covers were made to measure for these armchairs. The fabric selected was Porter and Stone Fabrics, a cotton/linen.
Custom made sofas | Contact BJU for more information | We make sofas to our customer’s requirements. Replicate classic and antique sofas and chairs or custom make a sofa based on one of our original designs to your specification. Reach out to Jo Griffiths to discuss. Shipping nationwide can be arranged.
A recliner chair we delivered to Darlington today. The fabric is P&S Balmoral Duck Egg Blue Check.
We can reupholster any chair in, almost, any fabric and what a difference a new fresh modern fabric can make. As you can see in this example.
We handmade a bespoke corner sofa to fit the exact space in this room. Fabric is a Linwood Omega Velvet, colour teal. We added soft fibre back cushions along with foam seat cushions in a soft grade with a fibre top.
Handmade sofas our speciality as well as reupholstery repairs.
Customer made sofas and chairs | Contact us with your requirements.
This is a nice two-seater sofa originally with loose covers. We suggested the sofa would look smarter reupholstered fixed. This way we can achieve a more tailored fit.
The fabric is Ross Aquaclean.
Here is a photo kindly provided by our customer showing the ‘Loose Cover Sofa’ back in its home.
The shape of this chair is adorable anyway, covered in newspaper it would still look good :). Here we have restored and reupholstered in a modern velvet with a contrasting back panel. Its something I would have not thought of. Our customer did and it looks great and we made a bespoke unique chair.
PS – You don’t just buy your soft furnishings do you? Design and build to your exact requirements.
How lovely it was to come down this a.m and see her sitting in the place she had occupied since 1970. We are quite overwhelmed. An absolutely incredible transformation. Barry’s experience is second to none. The frame adjustments have given a new comfort and her new dress is stunning. Jo from our first meeting, I knew we were in good hands. Your warmth and lovely manner is very special. Thank you.
We are so busy we are making an offer to customers who can wait until early next year for their furniture to be restored or reupholstered. You can save up to £500 on fabric when you book a reupholstery or restoration job. Go To The Offers Page
How to achieve up to a £500 saving
Ask us to quote you for your next job including fabric purchase from us and take a 10% discount from the RRP price of the fabric. A saving of up to £500.
This offer is for jobs booked in before 31st August 2020 to be collected in January 2021. Fabric can be selected at any time so you can take your time choosing the perfect fabric once the job is booked. We will post out as many samples you need. Read more about this offer.
About Our Fabrics
All our fabrics are of first quality, meet current legislation and come with a guarantee. We are stockist of some of the most versatile quality fabrics available in the UK and we have worked with most for over 20 / 30 years., for example, Chatsworth Fabrics, Linwood Fabric, Porter and Stone and Ross Fabrics.
Two very interesting and lovely chairs we reupholstered in flags. Stars and Stripes and the Union Jack. The best photo is the close up of the lion arm – see below. You may also be interested to see a chair we reupholstered in football shirts.
We were delighted to restore this contemporary Lounge Suite set for our customer. It had previously been re-upholstered by another company but our customer was never wholely pleased with it. It’s a very high-quality set therefore worth restoring again. The concern was, will it be right this time? Barry, our head upholsterer, stepped-in. He decided to redesign the reupholstery style based on the frame and his knowledge of this period brand. He bespoke tailor reupholstered the set based on the frame from scratch to restore it as the original. Our customer was delighted, relieved and pleasantly surprised. As we were too.
We work with bespoke manufacturers nationally to upholster their manufactured furniture and specialised soft furnishing.
We upholstered these units in a commercial vinyl.
Beech framed bespoke made to customers exact specification and dimensions. Made by us this bespoke sofa fits exactly in our customer’s kitchen. It is upholstered in AquClean – clean with water fabric. | <urn:uuid:bad44dc9-64e8-4d0a-9eee-d179b354cb22> | CC-MAIN-2023-40 | https://bjupholstery.info/category/custom-made/ | 2023-09-28T18:42:37Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.962391 | 1,010 |
Login to BlackFacts.com using your favorite Social Media Login. Click the appropriate button below and you will be redirected to your Social Media Website for confirmation and then back to Blackfacts.com once successful.
Enter the email address and password you used to join BlackFacts.com. If you cannot remember your login information, click the “Forgot Password” link to reset your password.
Gov. George Wallace granted a full pardon to Clarence ("Willie") Norris, the last known survivor of the nine Scottsboro Boys who were convicted in 1931 of the alleged rape of two white women on a freight train. | <urn:uuid:d6243164-4c09-482b-ae93-2872d00d875d> | CC-MAIN-2023-40 | https://blackfacts.com/fact/gov | 2023-09-28T16:46:49Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.871372 | 128 |
The Coleman Portable Camping Chair is the perfect companion for your outdoor adventures. Made of durable polyester, this chair features a comfortable and roomy 24-inch seat with a fully cushioned seat and back to provide maximum support and comfort. With a built-in 4-can cooler pouch, you can keep your drinks cold and within arm\’s reach.
Additionally, the chair features a convenient mesh cup holder and side pocket for quick access to personal items. The collapsible, folding design of the chair makes it easy to store and transport, and the chair\’s comfortable 18.1-inch sitting height makes it an ideal choice for camping, tailgating, picnics, and more.
This chair can support up to 325 pounds, and its sturdy construction ensures it will last through many outdoor adventures. Whether you\’re lounging at the beach or enjoying a barbecue in the park, the Coleman Portable Camping Chair will be your go-to for comfortable and convenient outdoor seating. | <urn:uuid:f19a87ca-8728-4610-9fa8-ac7a06221aff> | CC-MAIN-2023-40 | https://blackfridaybrand.com/coleman-portable-camping-chair-with-4-can-cooler-fully-cushioned-seat-and-back-with-side-pocket-and-cup-holder-carry-bag-included-collapsible-chair-for-camping-tailgates-beach-and-sports/ | 2023-09-28T18:45:14Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.917617 | 208 |
Right Answer Ding Ding Sound Effect
|Sample rate:||44.1 khz|
|Sound Size:||28 Kb|
|Category:||Game And Interface Sounds|
|Licence:||You can use the presented sound effects in your multimedia projects, both for commercial and noncommercial purposes, free of charge.|
This sound effect can be used in all creative projects in the recording studio, theater, radio, films animation, animated films, in addition to creating your own dubbing and music videos trailers, commercials presentations, speeches, shows, broadcasts, games, applications programmes, YouTube videos. | <urn:uuid:a8ac94a4-2095-40cb-8587-be2417aa59f2> | CC-MAIN-2023-40 | https://blanksound.org/right-answer-ding-ding-sound-effect | 2023-09-28T17:42:39Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.745229 | 178 |
Arizona's Tommy Lloyd was named the Associated Press men's basketball national coach of the year Friday, while Kentucky forward Oscar Tshiebwe was named the AP men's player of the year.
After serving as an assistant at Gonzaga for 20 years, Lloyd led the Wildcats to the Sweet 16 in his first season as head coach. Arizona had an impressive season, finishing with a 33-4 record after not reaching the NCAA tournament since the 2017-18 season.
Lloyd is one of three coaches to win the AP Coach of the Year award in his first season as a head coaching, joining Indiana State's Bill Hodges, who won in 1979, and Drake's Keno Davis, who won in 2008.
Expectations for the Wildcats entering the 2021-22 campaign were low. Arizona was unranked in the AP preseason poll and projected to finish fourth in the Pac-12. The Wildcats ended up finishing first in the Pac-12, won the Pac-12 championship and finished second in the AP Top 25.
As for Tshiebwe, he is just the second Kentucky player to win the AP Player of the Year award, joining current Los Angeles Lakers star Anthony Davis, who led the school to an NCAA title 2012.
"It is amazing to be join somebody like Anthony Davis," Tshiebwe said, according to the Associated Press (h/t ESPN). "And that gives me confidence and gives me more help for my future, too, for what I'm trying to do and what I'm trying to accomplish. I'm just putting God first because God knows what I need, and he has great plans for me."
Tshiebwe had an impressive 2021-22 campaign, averaging 17.4 points, 15.2 rebounds and 1.6 blocks per game while shooting 60.6 percent from the floor. His 15.2 rebounds per game were the most in Division I men's basketball since 1980.
Tshiebwe is now considering whether to return to Kentucky for another season or declare for the NBA draft. | <urn:uuid:0611609d-fbc7-4d75-bf27-710f745f9007> | CC-MAIN-2023-40 | https://bleacherreport.com/articles/10031442-oscar-tshiebwe-tommy-lloyd-named-ap-mens-basketball-player-coach-of-the-year | 2023-09-28T17:37:44Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.978794 | 422 |
The content discusses the importance of effective communication in various aspects of life. It emphasizes that communication skills are crucial for building successful relationships, whether personal or professional. The article also highlights the role of effective communication in the workplace, stating that good communication enhances collaboration, reduces conflicts, and improves overall productivity. Additionally, the content emphasizes the need for active listening and empathy to understand others better. It concludes by highlighting the benefits of effective communication, including better problem-solving, stronger connections, and the ability to convey thoughts and ideas clearly.
Source: The Root [ Read More ] | <urn:uuid:8a9f2699-da76-4bed-be63-02c244d8dac9> | CC-MAIN-2023-40 | https://blkish.com/leslie-odom-jr-discusses-purlie-victorious-and-his-performance-of-hamilton-for-obama-at-the-white-house/ | 2023-09-28T17:49:39Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.928315 | 115 |
CHICAGO — The warm, summery weather Chicago has been enjoying will stick around for awhile.
The city will see temperatures in the 70s through the weekend, with low chances for rain until June 10, according to the National Weather Service.
It was 88 degrees as of noon Wednesday, with a 20 percent chance of showers and thunderstorms after 1 p.m., according to the National Weather Service.
Thursday will be sunny with a high near 78 degrees and a small chance for showers, according to the weather service.
Friday will be sunny with a high near 77 degrees, according to the weather service.
Saturday and Sunday will keep the summer vibes rolling with sunny skies and daytime highs near 76 and 74 degrees, respectively, according to the weather service.
The beginning of next week will cool off just a bit with a Monday high near 73 degrees and a Tuesday high near 71 degrees, according to the weather service.
While the warm-up is mostly pleasant for now, the Chicago Office of Emergency Management and Communications is reminding neighbors that hot summer weather is coming — and to be “prepared for temperatures reaching dangerous levels throughout the summer season,” according to a news release.
Property owners and building managers must check their electrical and cooling equipment and make sure they are providing air conditioning in all apartments or a cooling area when temperatures exceed 80 degrees, according to the news release.
The city’s six public cooling centers are now open 9 a.m.-5 p.m. Monday-Friday, with the Garfield Center, 10 S. Kedzie Ave., serving as a 24-hour location, according to the news release.
Visitors are required to wear a face covering, which will be provided to those who don’t have one, according to the news release. The locations are below.
- Englewood Center, 1140 W. 79th St.
- Garfield Center, 10 S. Kedzie Ave. (24 hours)
- King Center, 4314 S. Cottage Grove
- North Area Center, 845 W. Wilson Ave.
- South Chicago Center, 8650 S. Commercial Ave.
- Trina Davila Center, 4312 W. North Ave.
The city’s libraries and Park District field houses are also open to folks looking to beat the heat, according to the news release.
Chicagoans can request wellness checks for their most vulnerable neighbors on hot days by calling 311, according to the news release.
Listen to “It’s All Good: A Block Club Chicago Podcast”: | <urn:uuid:53e3287d-d977-461b-a19b-7f9f0a635ac5> | CC-MAIN-2023-40 | https://blockclubchicago.org/2023/05/31/sunshine-and-temperatures-in-the-70s-sticking-around-as-city-gears-up-for-summer/ | 2023-09-28T17:39:56Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.937404 | 540 |
Sundance Film Festival: This Is Not a Ceremony is having its world premiere at the Sundance Film Festival (January 20–30, 2022).
‘This Is Not A Ceremony’
Ahnahktsipiitaa (Colin Van Loon)
Canadian Ahnahktsipiitaa, also known as Colin Van Loon, is Blackfoot and Dutch, hailing from The Piikani Nation.
His cinematic virtual reality production, “This is Not A Ceremony,” part of the Sundance New Frontier program, is described as “darkly humorous and occasionally caustic,” telling the story of Adam North Peigan, Robert Sinclair and others, and the struggles and conflicts of growing up as an Indigenous man, according to the Sundance website.
Van Loon is the lead artist, and the production included key collaborators Olivier Leroux, James Monkman and Jessica Dymond.
He grew up with his mother in Lethbridge and other southern Alberta towns in Canada.
“I really love our people, and when I say ‘our’ I mean Piikani and Niitsitapi as a whole,” he told Indian Country Today. “I am Blackfoot/Niitsitapi as well as Dutch. I am very Blackfoot-centric but try to remain inclusive to other nations and their ways. I wanted everyone to feel they were represented fairly.”
He was raised by his mother and grandmother, Edith North Peigan, whose name later became Van Loon.
“Edith was very much a victim of disenfranchisement, even though her husband, my grandfather Buddy Van Loon, was also Blackfoot through his mother, and our Kainai relations, the Holloway family,” he said.
Van Loon said nonetheless they remained close to their kin in the North Peigan family.
“When I was a younger man I was very close with Jimmy Small Legs, a cousin to Edith and me," he said. “Jim was able to show me a great deal of our Piikani traditions. This had major impacts on me growing up and it often shows up in my work. Jimmy and his wife Joanne adopted me in our Niitsitapi tradition, so I also refer to Jim as my grandfather and Joanne as my grandmother, as is common practice within The Blackfoot confederacy Piikani, Siksika and Kainai and Aamskapi Pikuni.”
The importance of family is evident in his work, he said.
“Family, kinship and reciprocity are values that show up in my work,” he said. “Adam North Peigan is my relation, and I wanted to showcase his story, as these moments are clear examples of systematic racism in Canada, and it’s an important story to tell in the framework of reconciliation.”
He continued, “There can be no reconciliation without truth, and both stories, Robert Sinclair and Brian Sinclair’s, and Adam North Peigan’s, are part of this. Additionally, Adam is a political advocate, working for our people and Survivors within the Sixties Scoop Indigenous Society of Alberta and the Legacy of Hope Foundation. I wanted to support him and his work in some small way.”
He wants the audience to leave with a sense of the impact of the virtual reality storytelling experience.
“I wanted both Indigenous and settler audiences to see the strength and resilience of Adam North Peigan and Robert Sinclair,” he said. “For White settlers specifically, I hope it affects them and they feel compelled to bear witness and try to make changes within the national community of Canada, to do something about systemic racism and discrimination.
“Virtual reality (VR) brings the audience closer to the storytellers,” he said. “hey can see them up close, hear what they have to say, and feel it not only in their minds, but viscerally and in their hearts as well. I want settler audiences to feel uncomfortable, and I want them to take that discomfort and think about it and act on it. I hope this connection makes audiences feel more compelled to uphold their responsibility as a witness.”
He continued, “I am hoping that Indigenous audiences will see the incredible strength, dedication and tenacity of Adam North Peigan and Robert Sinclair, with their continued efforts.”
Van Loon is the operations manager for the Indigenous Matriarchs 4 AR/VR media lab (IM4-Lab), and he sits on the Telefilm Indigenous Working Group, among others. He works to elevate the voices and stories of Indigenous peoples in his community by creating spaces for youth works in the Talking Stick’s Festivals REEL Reservation: Indigenous Cinematic Indigenous Sovereignty Series, or through his company, Blackfoot Nation Films. | <urn:uuid:a94b901d-1a52-4cc7-85cf-815b0ac838e3> | CC-MAIN-2023-40 | https://blog.americanindianadoptees.com/2022/01/film-this-is-not-ceremony.html | 2023-09-28T16:41:24Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.974983 | 1,022 |
Ancient8 is thrilled to announce our strategic partnership with Tearing Spaces, as both projects share a common vision of delivering exceptional and innovative gaming experiences to players worldwide. Together, we will push the boundaries of the gaming industry, creating unforgettable adventures that captivate and engage gamers on a global scale.
Introducing Tearing Spaces
Tearing Spaces is an immersive Play & Earn game that offers players a multitude of exciting opportunities to engage and earn rewards. In this thrilling game, players can form teams and participate in intensive 3v3 battles against real opponents from around the world. By showcasing their skills, completing tasks, winning tournaments, and owning NFT weapons with Token Boost capabilities, players have numerous avenues to earn valuable in-game tokens.
By utilizing NFT weapons, players can unlock a variety of activities, including League Matches and Special Events, to earn in-game tokens. Equipping an NFT weapon provides players with the opportunity to earn even more tokens as rewards. Additionally, completing Daily Tasks and climbing the ranks in the League system offer excellent ways to accumulate in-game tokens. The higher the league level, the greater rewards earned through exhilarating battles.
Ancient8 x Tearing Spaces
This partnership presents an opportunity for both Ancient8 and Tearing Spaces to develop and reward a loyal player base. Ancient8, renowned for its expertise in gaming infrastructure and its Web3 Gaming Loyalty Platform Space3, Dojo Launchpad, and Research Portal, joins forces with Tearing Spaces, an innovative blockchain game platform with a dedicated player community. Together, we aim to enhance gaming features, improve user experience, and onboard more players into the Web3 gaming ecosystem.
The future is bright as we embark on this journey hand-in-hand with Tearing Spaces. Ancient8 eagerly looks forward to the collaborative efforts that lie ahead, confident that our shared vision and combined strengths will pave the way for groundbreaking advancements in the gaming landscape.
About Tearing Spaces
Tearing Spaces is an AAA quality combat-style MOBA game for PC and mobile, featuring a non-fungible token-based system that rewards players with in-game tokens and rewards. Backed by Sino Global Games, the game offers a stunning art style and immersive 3v3 gameplay where players battle it out to earn unique and valuable achievements.
Ancient8 is a Web3 gaming infrastructure protocol. Ancient8 builds Web3 Gaming Loyalty Platform Space3, Dojo Launchpad, research content platform, and Vietnam’s largest guild to help Metaverse projects onboard millions of users to Web3. We’ve developed products to help 100+ web3 games and 200K+ users better navigate Web3.
Ancient8 has raised $10M in total financing from leading investors including Pantera, Dragonfly, Hashed, Makers Fund, C² Ventures, Mechanism, Coinbase, IOSG, Animoca, among others. | <urn:uuid:0157d8eb-c141-419b-91eb-a27d8895e5fa> | CC-MAIN-2023-40 | https://blog.ancient8.gg/ancient8-partners-with-tearing-spaces-for-an-unparalleled-gaming-experience/ | 2023-09-28T16:47:09Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.92503 | 597 |
A film review about the documentary Human that shows people from all over the world. While looking into their eyes, you will hear about life, love and suffering. Their stories will introduce you to other worlds. They will make you think about your own.
Taurus (April 20—May 20): Another year older, and yet still so much left to learn. Maybe you’d pick up a little more knowledge if you paused, took a deep breath and—wow, look at that! Someone besides you is talking. Let it happen a few times, just for fun. April Fool’s Prank: A day of silence.
Aries (March 21—April 19): It’s your time to shine, Aries, although I don’t see how that’s different from any other month. Maybe you should do everyone a favor and be a little less . . . yourself this month. Lucky numbers: the low value, quiet ones Taurus (April 20—May 20): You’re naturally stubborn in your
Pisces (February 19—March 20): Happy birthday, Pisces! As Jupiter oscillates in a random direction, you’ll experience surges of rage and suspicion. There’s no reason to rationalize these feelings. Channel them into a subtle passive-aggressiveness that will keep your friends on their toes. Compatible partner: Scorpio Aries (March 21—April 19): Two months into the year, and
Have you ever looked at a dancing young girl and smiled because she emitted such warmth and such joy? My two weeks at Aarti Home were spent experiencing just that. In 2014 I had the wonderful opportunity to begin my work with this organization. Aarti Home, located in the Kadapa district of Andhra Pradesh —
A poem to the boy who owes my heart some heavy-duty patches, and soon, before it heals all crooked For awhile you were happiness A type I had never tasted before Somehow familiar – like nutmeg and cinnamon, fragrant and warm – But somehow, with laughter words a body and soul Your taste
I am writing this because last week I had to write a letter to the mother of my dead best friend. I am writing this, because it has almost been a year, and I am still trying to process life, and lack thereof, and what it means when 18 year-olds die. I got an email
Mila Rosenthal sat in the kitchen of her apartment a week before the first air raid of her city: Berlin. Her son, Peter, was still asleep in his room. Mila set the kettle on the stove top and walked around aimlessly, humming to herself. As the water began to boil, she watched the steam rise. | <urn:uuid:fa717bc1-4c0b-4525-9112-92efbb6da870> | CC-MAIN-2023-40 | https://blog.berlin.bard.edu/tag/love/page/2/ | 2023-09-28T17:15:25Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.964351 | 565 |
Hello! It’s Friday, and we’re highlighting some of our favorite photos from Flickr Social this week. Join us over in Flickr Social, share some of your favorites to the photo pool, and you may see one of them highlighted in a future installment of ‘Weekly Snapshot with Flickr Social’!
“Basílica de la Mare de Déu de Lluc 1”- Jaroslaw
“Getting wider and closer”- Maxime Athier
“Demostrations 1”- Dominique Ducroquet
“Which Way?”- Jonathan Wolf
“Seen at The San Jose Jazz Festival 8/13/2023”- Charles McNeal
“let love in (U2 hotel)”- Tatyana
“Basset bleu de Gascogne”- Arthur Bouriaud
“Ponderosa Pit Stop”- rebecca Lammas
Our World Photography Day Contest has started!
Saturday, August 19th, is World Photography Day, and we are celebrating with a contest. We have some great prizes this year so head over to the official World Photography Day 2023 Flickr Group and check out the contest rules to get started. We can’t wait to see your photos!
Here are some of the winners from the last few years to get you inspired!
“Ruby throated Hummingbird”- Virginia Mitchell
“Look, I, I’m not just what you see”- Angelika Corral
“The Harpist”- Iko-Ojo Mercy Haruna
“art’otel cologne”- Achim Brandt
See you next week!
Not a Flickr member yet? Sign up today to join our community of photographers and find your inspiration. | <urn:uuid:58eb981d-b10e-40ac-9632-270dea2c512c> | CC-MAIN-2023-40 | https://blog.flickr.net/en/2023/08/18/weekly-snapshot-with-flickr-social-8-18-2023/ | 2023-09-28T17:01:17Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.80769 | 392 |
Locally Farmed Organic Vegetable Delivery
20 years of growing organic vegetables and delivering vegetable boxes from our 12-acre farm in Sussex.
What We Do
We produce organic vegetable boxes that are affordable, seasonal, and as fresh and local as possible.
We have different sizes of boxes available for various appetites, from individuals to families.
We are flexible with the items in your boxes. You can change items in your order for something you would like.
Our Organic Farm in Numbers
households per month
Why You’ll Love Us
There is never been a better time to eat organic. Organic means working with nature. We’re coming into a fantastic time for European food.
- Free delivery
“Love the flexibility”
Our Favourite Recipes
- How To Drive More Traffic To Your Shopify Store in 2024?Learn how to increase traffic to your Shopify store — for newly launched and established eCommerce businesses. With more than 30% of sales happening online, and eCommerce stores multiplying day by day, you can imagine the immense amount of competition … Read more
- Global Ecommerce Trends And Statistics For The Holiday And Festive Season 20232023 holiday and festive sales are going to be bigger than ever! Going by recent reports and statistics, eCommerce stores must start preparing to gear up for the season — deals & offers, discounts, gifts, flash sales, mobile campaigns, social … Read more
- Festive Season And Holiday Marketing Ideas Around The Shopify Customer Account PageThis year’s festive season is just around the corner. Have you started preparing for your Shopify marketing campaigns? If you’re wondering why prepare so early, and that there’s still a lot of time, you’re mistaken. Your competitors are prepping and … Read more | <urn:uuid:e7f9da7f-bd5f-4c56-927e-3dbd80e3fd58> | CC-MAIN-2023-40 | https://blog.getflits.com/25-2/ | 2023-09-28T17:15:02Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.878806 | 434 |
Earl, Marshall, and I went camping this weekend at a Men’s Retreat a couple of hours from here. We had a very relaxing time, made some new friends, and a good time was had by all.
Camping is a generous term; we actually stayed in the ranch lodge in a comfortable room. Camping facilities are available. Tents, RVs, and sheds converted to sleeping quarters, all outfitted with air conditioning, are scattered about the property. There were about 40 men in attendance this weekend.
We look forward to going back when the temperature is a little more moderate. | <urn:uuid:13fdfcf0-a0b4-4dde-8860-c32857ccf51e> | CC-MAIN-2023-40 | https://blog.jpnearl.com/2023/07/09/retreat-2/ | 2023-09-28T16:49:13Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.98283 | 125 |
We challenge you ... what's better than a warm, scrumptious berry muffin fresh from the oven? That's right, nothing!
Judging by the reaction this recipe got here at our home office, you might want to whip up a double batch of this delectable delight.
Be sure to share this fall-inspired recipe with friends and family!
This recipe yields approximately one dozen muffins.
½ c dried cranberries
1/3 c hot water
2 c all purpose, whole wheat or gluten-free baking flour
2 scoops Life’s Abundance Greens Blend
¾ tsp baking powder
¾ tsp baking soda
¼ tsp salt
1 tbsp orange zest (about 1 large orange)
1 tbsp unsalted butter, melted and cooled slightly
1 large egg, room temperature
2 tsp vanilla extract
1/3 c sugar, agave or liquid sweetener of choice
½ c plain nonfat Greek yogurt
1/3 c freshly squeezed orange juice (about 1 large orange)
¼ c non-fat milk
- Preheat the oven to 350°F, and lightly grease 12 standard-sized muffin cups.
- Re-hydrate the dried cranberries by combining with hot water into to a heat-safe bowl or mug. Let the bowl sit while preparing the muffin batter.
- Whisk together the flour, baking powder, baking soda, salt, Greens Blend and zest in a medium bowl. In a separate bowl, whisk together the butter, egg, and vanilla. Stir in the sugar or other sweetener. Add the yogurt and mix until no large lumps remain. Stir in the orange juice. Alternate between adding the flour mixture and milk, beginning and ending with the flour mixture, stirring until just incorporated. (For best results, add the flour mixture in 3 equal parts.) Drain the cranberries, and gently fold into the batter.
- Divide the batter evenly between the prepared muffin cups. Bake at 350°F for 17-20 minutes, or until barely golden brown and the centers feel fairly firm to the touch. Cool in the pan for 5 minutes before carefully turning out onto a wire rack.
Note: Fresh chopped cranberries may be substituted in place of the dried cranberries and water. | <urn:uuid:e800205d-1a78-41a0-a917-82d749024db0> | CC-MAIN-2023-40 | https://blog.lifesabundance.com/post/2017/09/06/verdant-cranberry-orange-muffins.aspx?realname= | 2023-09-28T18:06:22Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.871408 | 484 |
With warmer days ahead of us, chances are you’re ready to get outside and take advantage of those bright, sunny days. Doing so is also a great way to relieve stress and increase vitamin D.
However, if you’re not careful, over exposure to the sun’s harmful UV rays has the potential to damage skin cells, increasing the likelihood of skin cancer. This is especially true if you also frequent tanning beds or use sun lamps.
Since our skin is our largest and one of the most sensitive organs, it’s important that you protect yourself from sun damage this summer – and there are many ways you can do that. Some of these include using sunscreen, coverage from shade and even clothing to shield your skin from the increased sunshine.
“Clothing is a great option to protect your skin, such as longer sleeved shirts or pants,” Michele Ralofsky, MD, a family medicine physician at Mercy Health – Vermillion Primary Care, shares. “Even at a pool or beach, having a cover up with you can help you be sun safe. Accessories such as wide-brimmed hats can also allow for the protection of your face and eyes from the sun. Sunglasses can also aid in the protection of your face and eyes from the sun to reduce the risk of future cataracts.”
In addition to clothing, having a place to go for shade when at the beach or the backyard is another option to help keep your skin healthy while outside this summer. If you’re going to be in the sun for a long time, make sure you have a covered area to give your skin a break and make sure to reapply layers of sunscreen on exposed skin.
“Applying sunscreen that blocks both UVA and UVB rays from the sun that has an SPF of 30 or higher should also be part of your daily routine and done year-round,” Dr. Ralofsky states. “This is true even when the sun is not out. Reapplication of your sunscreen is also key to keeping your skin safe in the sun. You should always reapply your sunscreen if you’ve been outside for more than one hour, if you’ve been in water or if you are sweating.”
Dr. Ralofsky adds that it’s important to remember while each of these skin protection options work, they are most effective when you use them collectively to fully protect your skin from damage.
Skin cancer is the most common cancer in the United States. However, it can be prevented with sun safety and appropriate protections. Thus, it is critical to take care of our skin. While some people might be more at risk for skin cancer than others, the potential for UV rays to harm us can impact everyone.
Some skin cancer risk factors can include skin that burns or freckles easily, having light colored eyes, blond or red hair and certain moles on your skin that seem to be unusual. Also, knowing your family history of skin cancer and your sunburn risk can help catch signs of skin cancer quickly.
As summer quickly approaches, it’s a good time to think about your sun safety routine. No matter what your summer plans are, protection from the sun should always be a part of them. If you think you might be at higher risk for skin cancer, or you see any unusual changes to moles or your skin, it’s always important to contact your health care provider. | <urn:uuid:c3eaedb5-a30b-41ca-960b-b882eb7ea3dd> | CC-MAIN-2023-40 | https://blog.mercy.com/sunburn-prevention-treatment-tips/ | 2023-09-28T17:11:16Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.948896 | 720 |
The COVID-19 pandemic was just one of many crises we dealt with in 2021, and continue to deal with. Hurricanes, wildfires, heat waves, drought — in 2021, more than 40 … Read more
Visualizing wildlife and habitat data through maps presents a powerful opportunity to determine ways to help and identify trends. There is so much potential in understanding how we’re all connected through … Read more
We have much more to do and your continued support is needed now more than ever.
PO Box 1583, Merrifield, VA 22116-1583
The National Wildlife Federation is a 501(c)(3) non-profit organization | <urn:uuid:fde19e6c-c041-4890-8f4d-7b501a67e590> | CC-MAIN-2023-40 | https://blog.nwf.org/tags/mapping/ | 2023-09-28T16:54:46Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.921647 | 142 |
Have you spent half your life in a company car? Tired of your business, have you been monitoring your location? Then you need this hidden portable GPS jammer. Small electronic jammers can provide you with the privacy you need. After all, this is not always the case.
What makes the hidden portable gps blocker different? Such a powerful sector is rarely included in such a small economic plan. The jammer will block GPS activity within a 10 km radius, thus ensuring the privacy you need.
Who will buy a hidden portable GPS jammer? This unit is very suitable for couriers, sales staff and people who spend a lot of time on company cars or use company cars by themselves.
Why buy a hidden portable GPS jammer? Today is Friday night and you will go to a party or bar. The responsibility is to park the car in the parking lot and take a taxi back. But what will the boss think? Thanks to this device, he will never know him and will think he is locked in the garage where he must be stored.
It doesn’t matter whether you take your family on vacation or plan to leave your car in a dangerous place overnight. Your employer will never use this spoiler wisely. Protect your privacy with futuristic spy gadgets available today. | <urn:uuid:2ad33afc-130e-4f57-b204-56f32fdfbbd4> | CC-MAIN-2023-40 | https://blog.perfectjammer.com/2020/11/11/small-electronic-jammers-can-provide-you-with-the-privacy-you-need/ | 2023-09-28T17:23:56Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.946798 | 260 |
This device, designed by a team of researchers at the University of Chicago, is more effective than traditional jammers because it is worn by users. Make sure the chat room is no longer limited to listening to the movie, and don’t hide the microphone in the room. The great success of connected objects provides an opportunity for everyone to worry about snooping on their private conversations. A reasonable concern, because a Bloomberg survey revealed that the company’s employees unknowingly listened to the owner of a speaker equipped with Amazon Alexa’s virtual assistant.
If they had a thick bracelet designed by researchers at the University of Chicago, it wouldn’t happen. Equipped with an ultrasonic speaker, it projects a sound wave field around the wearer that humans cannot hear, but it will block nearby microphones. According to reports, Amazon employees did not hear the conversation record, but heard white noise.
Nowadays, some ultrasonic cell phone jammer work on the same principle, but since ultrasonic waves tend to travel in one direction, they are only effective for identified microphones. The speakers installed on the bracelet are also subject to the same restrictions: this is why the researchers placed them all around so that they can send radio waves in 360 degrees. For the same reason, they designed a jammer that can be worn on the wrist. Since we often speak while waving our hands, the ultrasound will be more dispersed, thus maximizing its effectiveness. | <urn:uuid:4f89cff6-8df9-43aa-b59a-99f122537dab> | CC-MAIN-2023-40 | https://blog.perfectjammer.com/2020/11/20/ultrasonic-jammers-work-on-the-same-principle/ | 2023-09-28T17:14:34Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.953887 | 293 |
Mobile phones were originally invented to talk to someone when needed. But over time, things have changed. Nowadays, mobile phones are not only phones, but also computers, portable entertainment devices, Internet terminals, wallets, GPS navigation items, movie theaters, etc. Now you can see that everyone carries a mobile phone with them every time they go everywhere, sit, walk, eat, shop, and party. So, have you noticed the problem now? When praying in the church, someone said loudly, would there be a problem with the phone? Is there a problem with the phone ringing when watching a movie in the cinema? Or, what if someone yelled to his cell phone in the library? Yes, we can now agree that misuse of mobile phones can cause serious problems. We need to find a way to stop using mobile phones in certain places. For this, we need cell phone jammer.
In the past few years, various types of jammers have been provided on many websites. They are different in size, shape, weight, power, interference distance and frequency range. If you want to use jammers on specific occasions, indoor blackout devices will be your ideal choice. Cell phone jammers designed for indoor use are very effective in blocking cell phone signals. When someone’s mobile phone bothers you, just turn on the jammer and the phone will stop working within a few seconds. In addition, you can also choose a jammer, which can cut different frequency bands: CDMA: 850-960 MHz, GSM: 1805-1880 MHz, GSM: 1920-1990 MHz and 3G: 2110-2170 MHz, which is very convenient. The interference radius of mobile jammers is between 5 and 50 meters. All phones in this range will stop working: their owners will not be able to make/receive calls and send/receive messages. In addition, mobile phone jammers are powerful because they are equipped with omnidirectional antennas that can block signals from different directions. We can guarantee that after turning on the jammer, you will not be disturbed in an environment without mobile phone interference. | <urn:uuid:df7a7d66-c4df-4a32-a53f-7ace80cc034d> | CC-MAIN-2023-40 | https://blog.perfectjammer.com/2021/01/13/cell-phone-jammers-are-very-effective-in-blocking-cell-phone-signals-2/ | 2023-09-28T16:39:47Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.957726 | 433 |
Disruption is the word in Silicon Valley. Almost every startup promises it: Uber with ride-sharing, TaskRabbit with odd jobs, Bodega with…bodegas. In corporate conversations, “disruption” means innovation, groundbreaking change, a better, cleaner future. It is valued above all else. Which is why there’s a violence to disruption, too—the rapid gentrification of the Bay Area by tech companies, the toxic chemicals contained in phones, the exploitative labor practices that keep corporations afloat. In her debut poetry collection microchips for millions, Janice Lobo Sapigao disrupts Silicon Valley itself, revealing the structural violence that is encoded into it.
In microchips for millions, Sapigao mixes personal memoir with the history of the Bay Area, drawing parallels between colonial and contemporary exploitation. The book opens with a page-long acknowledgement of the Muwekma Ohlone Tribe who first lived in the Bay. The “moment of recognition” is followed by a page of binary code, the language composed of zeroes and ones that is used by computer processors, and then ends with another recognition, “Let these pages allow empathy for the immigrant women and their families whose livelihoods are always, always at stake.” The exploitation of immigrant workers, and the gentrification of the Bay Area, are part of a lineage of trauma and theft that have occurred through the years on the land where Silicon Valley is now.
The poems in microchips for millions are multilingual: Sapigao includes English alongside binary code and Ilokano, the language of her Filipino family. She juxtaposes modes of communication, breaking down the meanings of words. In “the clean room” she lists the rigid uniform guidelines that factory workers like her mother must follow whenever they enter the workplace in parallel to quotes from conversations with her mother about work.“1. / hairnet / 2. / shoe covers / 3. / gloves,” is juxtaposed with, “‘they don’t like you / to wear sneakers. / they like you wear / the shoes they give you. / my feet is hurt.’ // ‘it’s hard to breathe, / sometimes. oh my god.’” This is a poetry of political refusal, the voice of immigrant women workers is the one that speaks most loudly, most vividly in this book. The corporate voice of Silicon Valley is left sterile, stripping the farce of its labor practices to their base cruelty: the workers don’t matter, but the microchips they make do. Sapigao quotes official sources, “A clean environment is designed to reduce / the contamination of processes and / materials. This is accomplished by / removing or reducing contamination / sources,” then adds, personally, painfully, “my mother is contaminated.” Behind the wealth, the technological innovation, is the terrible precarity of immigrant women workers—the labor exploitation, the fear of being fired without benefits, of being caught organizing a union.
One poem, “the start-up,” is structured in the shape of the 101, the freeway that traverses the entire state of California. Two black lines in the center of the page filled with binary code mark the freeway, which is lined on either side with boxes filled with text that represent buildings. One side of the freeway chronicles a reality show about Silicon Valley entrepreneurs, and the other shares the history of East Palo Alto, a city left behind by the tech boom. In the corner of the page there is a small note: “map not drawn to cartographic or traumatic scale.” It’s impossible for the page to hold the many histories of trauma that have happened on this land, but Sapigao draws the map anyway.
The whole of Silicon is contaminated, by the tech companies and the toxic fumes that emit from their factories. Sapigao documents this in screenshots of Google maps of the Bay Area that appear in intervals throughout the collection. The maps are layered—one pictures San Jose, the map marked with purple oblongs and dots that indicate chemical plumes. Overlaid in white text, Sapigao has written, “strange leftovers.” Sapigao won’t let Silicon Valley’s leftovers go unmapped. Near the end of the book she asks, “what do we do with / a map?” One answer might be, turn it into a poem. Gather the leftovers, the marginalized stories, and erased voices that have been left off the map, and write them down in a new language. | <urn:uuid:6b064868-b035-4778-ac0a-76f7bf6b5081> | CC-MAIN-2023-40 | https://blog.pshares.org/disrupting-silicon-valley-in-janice-lobo-sapigaos-microchips-for-millions/ | 2023-09-28T18:06:35Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.937992 | 966 |
Microsoft’s AppFabric for Home windows Server is middleware consisting of two important options, AppFabric Internet hosting deploy and handle Home windows Workflow Basis (WF), workflows which are hosted in Home windows Communication Basis (WCF) companies. Moreover, it accommodates an extension for IIS that permits efficiency and workflow monitoring together with PowerShell instructions to handle persistence, internet hosting, and monitoring duties.
AppFabric caching, the second important characteristic, is an in-memory, distributed cache that runs on a number of on-premises servers to supply a efficiency and scalability enhance for .NET Framework functions.
AppFabric caches saved knowledge in key-value pairs utilizing the bodily reminiscence throughout a number of servers.
AppFabric makes use of Microsoft’s mounted lifecycle coverage, which signifies that mainstream assist for AppFabric 1.1 ended on April 11, 2017. Prolonged assist lasts till April 12, 2022. Microsoft has added one further notice:
AppFabric 1.1 for Home windows Server assist ends on the date indicated except distributed as a element of SharePoint Server 2013, 2016, and 2019. Parts obtain the identical assist as their mum or dad product or platform.
To exchange AppFabric, Microsoft has created a migration information, detailing which merchandise Microsoft recommends utilizing. This primarily consists of the utilization of NCache or Redis Cache companies. Please click on right here to learn extra about it.
NCache is an Open Supply in-memory distributed cache for .NET, Java, and Node.js. NCache is extraordinarily quick and linearly scalable and caches utility knowledge to scale back costly database journeys. Use NCache to take away efficiency bottlenecks associated to your knowledge storage and databases and scale your .NET, Java, and Node.js functions to excessive transaction processing (XTP).
On this article, I’m going to elucidate how you can Use NCache as AppFabric various.
Set up NCache Supervisor
Obtain NCache from NCache Obtain Middle (alachisoft.com). I extremely suggest you to put in the Enterprises version as a way to discover all of the options. Earlier than the set up be certain .NET 6 has been put in in your machine.
After finishing the obtain and set up course of, you’ll be able to run the NCache Net Manger within the bowser from localhost 8251 port, as proven within the beneath determine.
We will create a clustered and native caches from the NCache Supervisor utility.
For this demo, I’ve created a neighborhood cache and named it “myLocalCache” utilizing Ncache Supervisor as proven within the beneath determine.
Click on right here to verify how you can create a neighborhood Cache utilizing NCahce Net Supervisor.
Let’s do the stress check to verify our cache standing. Run beneath command in command immediate to begin the stress check
“test-stress <Cache Identify>”
Now the stress check has been accomplished, verify the rely from cache statistics. You’ll be able to go to Cache statistics by deciding on our cache from NCache Net Supervisor and clicking on the statistics icon.
The best way to Use NCache as AppFabric various?
There are some particular the reason why NCache is used as a greater various for AppFabric. As a result of it’s 100% native .NET and runs on home windows platform, the oldest and extra steady .NET distributed cache with totally supported official .NET and Java Purchasers and is way more highly effective.
We’ve two choices emigrate AppFabric to NCache
- Utilizing AppFabric wrapper
- Making Direct NCache API Calls
Utilizing AppFabric wrapper
No code adjustments are required whereas utilizing AppFabric wrapper, simply by putting in the wrapper package deal and changing the Namespace will do the job to go.
Making Direct NCache API Calls
It requires code adjustments however no logic adjustments are required and it is extra highly effective with NCache options.
Notice: We will use AppFabric Wrapper and NCache API’s can be utilized aspect by aspect.
Utilizing AppFabric Wrapper
Simply observe three easy steps emigrate from AppFabric to NCache
- Obtain and Add NCache SDK package deal from Nuget Package deal Supervisor
- Obtain and Add NCache Wrapper Nuget Package deal
- Exchange AppFabric Namespace with NCahce Wrapper
1. Add NCache Nuget Package deal
Open your current AppFabric challenge in your visible studio and Set up Alachisoft.NCache.SDK package deal from NuGet package deal supervisor.
2. Obtain NCache Wrapper for AppFabric
Set up AppFabric.Wrapper.NCache NuGet in your utility. After putting in the Nuget package deal in your AppFabric utility, consumer.ncconf and config.ncconf information shall be included in your challenge.
3. Exchange AppFabric Namespace with NCahce Wrapper
Make the next adjustments in your utility .csproj and .cs information.
Take away the references to the next AppFabric libraries,
Exchange the next namespaces with Alachisoft.NCache.Information.Caching within the utilizing statements of your supply information,
After finishing all of the steps, you need to use different extension strategies from NCache library.
Now you must be capable of run your AppFabric utility utilizing NCache because the distributed caching resolution.
For reference please verify this challenge supply from GitHub.
We noticed what’s NCache, how it may be a greater various for AppFabric and the way it is extremely emigrate the AppFabric app to NCache because the distributed caching resolution. We’ll see extra about NCache in my future articles | <urn:uuid:db27f7ec-3440-40ce-99c9-9ccd28c03eb0> | CC-MAIN-2023-40 | https://blog.skrots.com/replacing-appfabric-with-ncache/ | 2023-09-28T17:29:16Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.836208 | 1,310 |
You’re a little ways into your first programming job, and things are getting easier. At first, all the code you had to deal with might have overwhelmed and confused you, but you’re starting to get the hang of it. That’s great! Now you’re wondering how to take the code you write to the next level. While there are lots of things to learn about your programming stack, many of which will make you a better programmer, there are a few that will serve you no matter what stack you work in. One of those is code documentation.
Many developers don’t write enough documentation, either because they don’t see the value or because they feel like they don’t have time. You don’t need to be one of those developers. With a little time and a lot of practice, you can add documentation for your code that makes reading it a joy to use for both you and anyone else who comes along.
Good Documentation Comes in Many Forms
When most developers think of code documentation, they think of comments. Comments can be valuable additions to code, but they’re not the only definition of documentation. Documentation is anything you write in addition to your code to help someone else understand how it works. You might not think of it this way, but a good example of code documentation is a README file. A good example of basic documentation is the Express.js README file. It answers several important questions about the framework and tells you how you can include it in your project, how to install it, and how to run tests.
Good documentation can come in the form of API documentation too. Once again, Express.js provides a great example. This version of documentation is more of a reference library for developers using the framework. You’ll find answers to questions about what individual functions do and what different parameters to those functions mean. Without that quality documentation, Express wouldn’t have nearly as many teams using it as they do.
And of course, you can use in-line comments to document code too. Those kinds of comments usually aren’t used to teach people outside of your own team about the code. Instead, they’re useful to explain what’s happening in a particular bit of code to your teammates or to your future self.
Why You Should Document Your Code
As noted above, many developers don’t understand the purpose of code documentation. They’ll argue that good code should be self-documenting and that you shouldn’t need to explain it. These people are, in a word, wrong. The truth is that good documentation is an essential part of any code base. Why? Because people shouldn’t need to read all of your code in order to understand what it does. “People” in that previous sentence can refer to anyone, including your future self.
The truth is that often, the “people” who’ll need to understand code after it’s written is you. That little bit of logic that seemed so clever when you wrote it six months ago might be difficult to understand today. If your code is well-documented, you don’t need to spend time trying to understand what it does. You’ll be able to spend a few seconds looking at the description and then get back to what you’re working on right now.
If you’re lucky enough to be working on code that’s used by dozens or hundreds of developers, good documentation is even more important. Your users’ lives will be significantly improved by your time spent writing good documentation, and they’ll thank you for it. Literally!
The key to remember is that good documentation saves more time than it takes to write it. It might be your time, or it might be the time of team members, or even people you’ll never meet. Sometimes, writing documentation will even help you recognize a part of your code that’s too complicated so you can simplify it.
Some Common Documentation Mistakes
As a junior developer, you’re going to have to spend time learning what makes documentation effective. The good news is that you can learn from people who’ve gone before you so you can avoid common mistakes.
One common mistake I see with code documentation is to document information that’s already clearly visible. For instance, lazy developers will add “documentation” to a function by adding a block that provides the name of a function as well as the names of each parameter and their individual types. This type of documentation is useless! It takes seconds for someone to read the name of the function and the parameters it takes. That’s not documentation, it’s just repetition. Instead, the documentation should include a quick bit of information about what the function does and how each parameter changes the function’s behavior or why it’s needed.
The opposite pattern can also be a serious problem. To avoid writing too little documentation, some developers like to write out the explanation for every tiny bit of logic that’s contained in a function. They meticulously document every rationale that went into creating the function. By the time they’re done, they might have spent as long writing the function as they did writing the documentation. What’s worse, the documentation is often difficult to understand and takes just as long as reading the code. That kind of documentation is also a waste of time. Instead, good documentation gives a basic explanation of both the what and the why. If there are any particularly tricky parts of the code to understand, then documentation should explain just those parts.
Relying on Tests to Document
Occasionally, you’ll run across someone who argues that the best form of documentation is unit tests. That approach has a major shortcoming: reading unit tests is often just as difficult to do as reading code itself. Any developer wishing to learn what your code does will have a big first step while they hunt down and read all of your unit tests. Many will just give up before achieving what they set out to do. While unit testing is a valuable addition to any code base, it’s not a replacement for good documentation.
Ways to Take Documentation to the Next Level
If you work on a big code base, code documentation can feel daunting, especially if you haven’t been diligent about documenting code up to this point. It might feel like you’re trying to boil the ocean. If you have a big code base, or one where you know good documentation is critical, you might want to investigate automated code documentation tools. These tools drastically simplify the process of writing consistent, good documentation for an entire team. A tool like GhostDoc will intelligently look at your code and use templates established by your team to kick-start your documentation with a couple of key presses. Automated documentation tools remove one of the other common reasons to oppose writing documentation: it takes too much time.
Once you have consistent documentation, other tools enable you to share that documentation easily. Automated documentation tools take the pain out of developing good documentation for things like public APIs that your code provides.
Get Started Today
Writing great documentation is a lot easier than writing code. Unlike code, documentation isn’t an all-or-nothing enterprise. Start with a goal to write good documentation for one function every day. That kind of practice builds healthy habits, and you’ll see the payoff down the road when you spend a lot less time trying to understand parts of your code base. Over time, it’ll start to feel wrong when you write code that doesn’t have good documentation. You’ll start pointing out ways to improve documentation to your coworkers during code review. One little habit will improve your team’s code for your entire business.
Learn how GhostDoc can help to simplify your XML Comments, produce and maintain quality help documentation. | <urn:uuid:6d327108-b476-48a0-9eea-ea90374b60c9> | CC-MAIN-2023-40 | https://blog.submain.com/code-documentation-the-complete-beginners-guide/ | 2023-09-28T18:57:46Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.928653 | 1,655 |
As a small business owner, you're juggling many things, from research and marketing to sales and inventory. But when it comes to finances, don't let them take a backseat - they're the backbone of your long-term success. Managing your finances is essential for achieving your goals, and taking control of your money can be empowering.
In today's competitive business landscape, smart money decisions can set you apart. From planning and strategy to execution and progress monitoring, each step counts.
We spoke with Rebecca Trudgett, Business Strategist, Charter Tax Advisor, and Founder of Switchfoot Accounting, to find out the five key things small business owners need to know to take control of their finances and boost their chances of success.
- Prioritise planning and strategy: To take control of your finances, you need to know where you're headed. Ask yourself: "Where am I now?" "Where do I want to be? What will get me there?" Create two one-page plans, one for personal goals and one for business goals. Keep it simple and focused on charting a course based on the business goals, purpose, and vision.
- Execution counts: When working for yourself, accountability is crucial. Having someone to hold you accountable can help keep you on course and make intelligent adaptations when your plan changes. Seek support from a coach, the Inspiration Space, or your accountant.
- Don't forget profit margins and pricing: To start, figure out what you need from your business, including salary expectations, pension, work/life boundaries, and overheads. Based on that, calculate how much product/service you need to sell and at what price to reach your break-even point. Then, work out how much you need to sell above and beyond the break-even point to reinvest in the business and deliver the lifestyle you're after.
- Cash flow: Get in the habit of saving money in your business as you go. Set aside an appropriate percentage in a separate bank account every time you sell something. This tactic is helpful for saving 10% each month for your tax bill or annual expenses.
- The power of 1%: When trying to grow a business, it's easy to feel overwhelmed. Instead of focusing on massive growth, think about increasing your turnover by 1% every day. This consistent approach to small increases will compound and help you achieve your goals more quickly.
By prioritising planning and strategy, seeking accountability, focusing on profit margins and pricing, managing cash flow, and embracing the power of small gains, you can take control of your finances and set yourself up for long-term success. | <urn:uuid:a36dfdd5-fe13-432f-a371-031dc2576d94> | CC-MAIN-2023-40 | https://blog.theinspirationspace.co/5-things-to-know-about-finance/ | 2023-09-28T18:09:51Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.94822 | 534 |
Travelling St. Andrews, Scotland
Travelling St. Andrews – A Town Full Of Character
Whilst travelling St. Andrews I heard an interesting statistic – only one in ten people who visit St Andrews actually play golf there. This totally surprised me, as I had just assumed that golfers would be the main visitors in a city that is essentially the home of golf. With this statistic in mind, I set out to find out what St Andrews has that attracts the nine out of ten people who don’t come to play golf…
St Andrews has character
St Andrews is positively brimming with character. It has atmospheric Cathedral ruins, which I highly recommend taking a walk around. It’s free to enter and the ruins are remarkably well preserved given that it dates back as far as the 12th century.
As well as cathedral ruins, there are also the ruins of St. Andrews Castle to explore. It also dates back to the 12th century and sits in a picturesque position overlooking the North Sea.
However, it isn’t just the historical ruins that are full of character – the houses, university buildings and even the random everyday buildings here are gorgeous. It made me want to pull out my camera at every turn while walking through the small streets of the city.
St Andrews has GREAT food
During our few days travelling St Andrews we enjoyed some seriously delicious meals. We sampled Nahm-Jim, a Thai and Japanese restaurant that is a favourite haunt of celebrities and locals alike. There weren’t any celebrities in that evening, but the food was brilliant and there were lots of clean plates at our table!
We also enjoyed a relaxing Sunday lunch at Mitchell’s Deli and Cafe who strive to use only local, fresh ingredients wherever possible in their cafe. I always love discovering places that use fresh, local ingredients as I believe it’s important to help independent businesses at home and when I’m travelling. My hands down favourite meal during my time in St Andrews was at The Doll’s House, a cosy but elegant spot where William and Kate are said to have enjoyed regular date nights. Their sticky toffee pudding was the best I’ve ever tasted and, trust me, I know my sticky toffee pudding!
The people are friendly I’ve written before about how Scottish people are friendly, it’s one of the things I love about Scotland, but the welcome we received when travelling St. Andrews was second to none. Everywhere we went people greeted us warmly, chatted to us and were happy to recommend places to go and things to do within the city. Their enthusiasm was infectious and it was definitely something which made me feel at home there. It was refreshing, charming and something which everyone in our group commented on.
It’s naturally beautiful
The one thing that really stuck out for me when travelling St. Andrews is how breathtakingly beautiful it really is. Despite visiting in January, we enjoyed blue skies, a touch of sunshine and remarkably warm temperatures. I was even walking along the beach without a jacket!
My one and only complaint about our time travelling St. Andrews was having to leave! I really fell for this small city, and I’m kicking myself for never having visited before now. It’s peaceful, charming, welcoming and utterly gorgeous, and I’m already planning to return in summer. Travelling St. Andrews was certainly an experience I’ll never forget and one that I’ll treasure forever.
Emma shares all of her travel adventures, tips and advice on her two websites Emma’s Travel Tales and Emma On Board, as well as writing for a number of other online publications. She has also partnered with many large companies and tourism boards around the world. She’s busy making memories around the world…
I’m Emma, a twenty-something Scottish girl who’s obsessed with travel.
I’ve been to 38 countries so far and had some incredible adventures around the world.
My passion for travel and writing led me to create my person blog Emma’s Travel Tales. | <urn:uuid:29e174cc-f710-4d3d-8b09-3cfd54ea0280> | CC-MAIN-2023-40 | https://blog.tripsology.com/europe/emma-gray/travelling-st-andrews-scotland/ | 2023-09-28T17:51:21Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.96941 | 852 |
It will be mandatory to report on SAF-T format to the tax authorities from January 1, 2020.
The introduction of SAF-T in Norway has been a "buzz" these days. We have seen articles in media. In addition, there are many consultants that offer to help companies to become SAF-T compliant before the deadline. We experience increasingly questions about both when the requirement of reporting on SAF-T will be due and not at least what it means for the individual business. Our advice to you is: "don't panic". The requirement to report on SAF-T format is postponed to January 1 2020 or later.
What is SAF-T?
SAF-T is an abbreviation for "Standard Audit File-Tax" and is based on an OECD template. There are several countries in Europe that have introduced a form of SAF-T reporting. Unfortunately, the there are many differences between the implementation in different jurisdictions. For further information please see our previous blog
In connection with the digitization and automation of controls, the tax authorities will request that financial information is reported online in an xml. format.
In the first phase of SAF-T, mandatory from January 1 2020, the tax authorities will upon an audit request that the general ledger and the customer and supplier specifications (sub ledgers) are provided in xml. format. Upon request, the required documentation will be delivered through www.altinn.no (public portal for exchange of information)
It is our understanding that the SAF-T reporting requirement will be expanded. See the illustration of the timeline below:
Pros and cons of the SAF-T reporting
One of the purposes of the SAF-T format is to establish a standardized template for exchanging financial information between companies and other stakeholders. When the businesses are able to report in a SAF-T from at their accounting system, it will also make it easier to change accounting system.
For the Tax Administration, the reporting via SAF-T implies the possibility to automate controls. That will lead to more frequent controls performed more efficient. In our view the companies should therefore perform more automated controls over their accounting data to verify their compliance with the VAT regulation. If errors are identified and corrected before the tax authority perform a control, no penalty tax will be levied.
For the auditor it will also be an advantage to be able to extract accounting data in a standardized format. This will simplify the auditor's ability to make standardized analyses.
What is important to keep in mind?
Basically, the Tax Administration have assumed that system vendors ensure that accounting systems are able to deliver information in an xml. format. I.e., the system vendors have to ensure that their accounting systems complies with SAF-T.
Companies that are subsidiaries of international businesses or have in-house development systems, can not rely on the system vendor to ensure their SAF-T compliance. In such cases a SAF-T converter may be required. However, "don't panic" it is two years before the requirement enter into force. However, the Companies should start the process to identify how they can be able to report in the xml. format.
The requirement to provide financial information on SAF-T-format only applies upon an audit in the first phase. Based on dialogue with the Tax authority, it is our understanding that a Company is compliant if it is able to produce financial information on SAF-T-format within reasonable time after notification of an audit.
Expectations to the extension of the scheme
In the first phase SAF-T requirements are limited to that general ledger, accounts receivable and accounts payable can be made available in a standardized electronic format. Based on the limitation in the requested information in phase one, the SAF-T reporting will be relevant for VAT-controls. We expect extensions of the reporting obligations to other areas.
The Tax authority has nominated an administrative body to develop SAF-T further. Both the association for auditors and accountants in Norway will participate in this administrative body.
Based on the signals we have received from the Tax authority, it is expected that the system of reporting on the standardized format will be expanded and in the long run take place more regularly. We therefore recommend to find a solution that is robust for:
- extensions of the requirement of reporting and
In most cases the system supplier have the responsibility to ensure SAF-T compliance
The system supplier must update their systems in order to be SAF-T compliant. It is therefore important that the businesses have a dialogue with their system suppliers about their roadmap to ensure that accounting systems will be SAF-T compliant before January 1 2020. We also recommend that you challenge your system suppliers on how future extensions of SAF-T are handled.
For those businesses that have developed self-improvement systems, or other systems where one can not expect that system supplier ensures compliance with the SAF-T, it is now time to plan for how to be compliant within January 1 2020. It is not a requirement that SAF-T reporting must be an integrated part of the existing system solutions. It is possible to prepare reports on SAF-T-format with your own SAF-T-converters.
Use SAF-T as a leverage to ensure the quality of the VAT-reporting
Even though the deadline to comply with SAF-T is January 1, 2020, the business should as soon as possible after the SAF-T-functionality is in place in your accounting systems perform checks of the VAT-reports.
We recommend that businesses performs automatic control of its data material to ensure the quality. Based on our experience, it will be easy to uncover:
- differences between VAT-reporting and accounting,
- double bookkeeping of invoices,
- the appropriate VAT-treatment of purchase of services from abroad,
- the use of appropriate VAT rates and
- errors in deductions as some examples.
As mentioned above, errors that are corrected before an audit will normally not lead to penalty tax.
This blog post is written by Marit Barth and Torkil Hindberg.
Jeg heter Marit Barth, og er partner/advokat i Advokatfirmaet PwC. Jeg har jobbet med mva for næringsdrivende og selskaper siden 2003 og har lyst til å blogge om mine erfaringer på dette området. Mitt mål er å gi deg informasjon, analyser og nyheter på en annen måte enn det du får gjennom nyhetsbrev og annen faginformasjon. Jeg håper også at jeg noen ganger klarer å inspirere deg, utfordre deg og kanskje provosere deg litt. Hvis du har synspunkter, innspill, kommentarer eller spørsmål til noe du leser eller ser her på bloggen blir jeg glad for å høre fra deg.
Velkommen til #norgesskatteblogg.
My name is Marit Barth and I am a lawyer and partner in PwC Tax & Legal Services. I have been working with VAT since 2003, and I would like to blog about my experiences in this area. My goal is to give you information, analyses and news in a different way than you get through newsletters. I also hope that I sometimes manage to inspire you. If you have input, comments or questions to something you read, I will be happy to hear from you.
Welcome to Norway’s Tax blog. | <urn:uuid:285880ae-02d3-4f6c-b9d8-e9346f5368ff> | CC-MAIN-2023-40 | https://blogg.pwc.no/skattebloggen-en/introduction-of-saf-t-in-norway-postponed-to-2020 | 2023-09-28T17:49:55Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.922165 | 1,587 |
The Rev. Dana Nelson and Tom Ososki are nearing the end of their service as ELCA missionaries in Peru. To support any of the ELCA’s over 200 missionaries in the global church, go to www.ELCA.org/missionarysponsorship.
June 1, 2013
Greetings from Talitha Kum (Little Girl Get Up!) Lutheran Church in Cusco, Peru. We have exciting news to bring to you. The Sembrando para el Futuro (Sewing Seeds for the Future) program started up again the first week in May and is now in full swing. We are excited to report that the congregation is providing nutritious breakfast to 50 children (and two elders) five days per week.
Italo is 13 years old. He is wearing his red school uniform, sitting next to the tiger in the photo. He rents a room a few blocks from the church and lives alone (without parents). Thanks to the Sembrando program starting up again, neighbors told us about Italo and invited him to breakfasts and into the life of the church.
This year we collaborated with the local health post, and nurses came to Talitha Kum to measure the height and weight of all the kids so we can mark their progress during the year to see if the Sembrando program is helping them to grow. The nurses found that six of our children have “chronic malnutrition” or are “at risk of chronic malnutrition.” So it makes Sembrando para el Futuro feel all the more urgent.
Thank God for teachers! We are so grateful to have found Alicia, who is a second-year student at a teachers training institute in Cusco. She comes to our congregation four days per week to tutor the Sembrando children, especially the ones in second through sixth grade, since those are the grades Alicia is being trained to teach.
We have windows! Upstairs and downstairs and even way up in the parsonage on the third floor of the church we have all of the windows and doors installed now, so everyone is warmer. Tom painted the windows in the sanctuary red, blue, white, purple and green — the colors of the church seasons. When we have worship in the morning, the colors are projected onto the floor by the sun and move across the sanctuary as the earth turns. It’s so pretty!
I can’t believe we will only be here in Cusco for four more Sundays before we move back to Minnesota. We are going to miss Peru very much. Thank you for making it possible for us to have served here in the church since 2007.
Que Dios les bendiga muchísimo.
Even though we won’t be living here as missionaries in Peru in the near future, we encourage you to keep Talitha Kum and all the congregations of the Peruvian Evangelical Lutheran Church in your hearts and prayers.
Dana, Tom, Tana and Anthony | <urn:uuid:21256131-557e-47c3-a5f2-5db1fbdcf4d9> | CC-MAIN-2023-40 | https://blogs.elca.org/handinhand/nurturing-and-nutrition/ | 2023-09-28T17:25:25Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.958237 | 621 |
|Register by scanning the QR code below or going to https://go.umd.edu/IWM|
CANCELLED! Due to Virginia Tech’s response to COVID-19 and out of concern for everyone, we are cancelling all of these workshops. We will reschedule after field season in Nov. or Dec.
- Herbicide Resistance- What is it and how did we get here?
- Creating Effective Herbicide Plans
- Integrated Weed Management of Palmer amaranth, common ragweed, and horseweed/marestail
- Local Perspective on Weed Management
- Putting It All Together: Creating a Weed Management Plan
CCA credits will be offered
Free lunch to start or end the program!
If you are a person with a disability and desire any assistive devices, services or other accommodations to participate in this activity, please contact the Extension office listed above or TDD* during business hours of 8:00 a.m. and 5:00 p.m. to discuss accommodations 5 days prior to the event. *TDD number is (800) 828-1120.
Virginia Cooperative Extension programs and employment are open to all, regardless of age, color, disability, gender, gender identity, gender expression, national origin, political affiliation, race, religion, sexual orientation, genetic information, veteran status, or any other basis protected by law. An equal opportunity/affirmative action employer.
The 2020 Northern Neck Crops Conference will be held Thursday, Jan. 16 at the Cobham Park Baptist Church, 13829 History Land Hwy Route 3, Warsaw, VA 22572. This year’s conference will include pesticide certification training, updates from FSA, NRCS, and SWCD, and several Specialists and Agents from Virginia Cooperative Extension that will cover a wide variety of topics. We look forward to seeing your there for a great day of learning and interaction with the experts. Lunch will be provided. Agenda detail are below.
Full Attendance to the conference has been approved for Private Pesticide Applicator Recertification in Category 90 & 91, and Commercial Categories 1A, 10, and 60. The conference has also been approved for 1.0 Virginia Nutrient Management CEU and 4.0 CCA-CEU credits.
9:00 – 9:05 Welcome – Trent Jones, VCE – Northumberland & Lancaster
9:05 – 9:50 Using Cover Crops for Weed Control – Michael Flessner, VCE – Weed Science Specialist
9:50 – 10:35 Market Update Robert Harper, Virginia Farm Bureau -Grain Division Manager
10:35 – 10:40 Irrigation Resources – Julie Shortridge, VCE – Biological Systems Engineering Specialist
10:40 – 10:55 BREAK – Please visit with our sponsors!
10:55 -11:40 IPM Updates – Sally Taylor, VCE – Entomology Specialist
11:40 – 12:35 Weathering the Storm: How to Cultivate a Productive Mindset – Jeremy Daubert, VCE – Rockbridge County
12:35 – 1:15 LUNCH
1:15 – 1:20 Program Updates – Scott Hammond, NRCS – Soil Conservationist
1:20 – 1:25 Program Updates – Brandon Dillistin, NNSWCD – District Technical Manager
1:25 – 2:15 Corn and Small Grain Production Update – Wade Thomason, VCE – Grains Specialist
2:15 – 2:30 Break & Evaluations
2:30 – 3:00 Legal Updates – Robert Christian, Pesticide Investigator – VDACS
3:00 – 3:30 Safety Updates – Trent Jones & Stephanie Romelczyk, VCE – Northern Neck
3:30 – 3:40 Wrap Up & Paperwork
The 2020 Five County Agricultural Conference will be held Wednesday, Jan. 15 at the King William Ruritan Club Building, 156 Ruritan Lane, King William, Virginia 23086. This year’s conference will include pesticide certification training, updates from FSA, NRCS, and SWCD, several Specialists and Agents from Virginia Cooperative Extension that will cover a wide variety of topics, and precision agriculture round-table discussion. In addition, you will be able to get your dicamba herbicide certification with training being offered by Don Cline of BASF. We look forward to seeing your there for a great day of learning and interaction with the experts. Lunch will be provided. Agenda detail are below.
Full Attendance to the conference has been approved for Private Pesticide Applicator Recertification in Category 90 and Commercial Categories 1A, 10, and 60. The conference has also been approved for 1.5 Virginia Nutrient Management CEU, 2.5 Integrated Pest Management and 1.5 Crop Management CCA-CEU credits.
7:45 a.m. Registration
8:15 a.m. Grain Market Update, Robert Harper, Manager, Virginia Farm Bureau Grain Division
8:45 a.m. Corn Update and Hybrid Selection – Dr. Wade Thomason
9:15 a.m. Break
9:30 am. Soybean basics and Soybean Variety Selection- Dr. David Holshouser, Extension Soybean Agronomist
10:00 a.m. Crop Fertility and Fertilizers – Dr. Hunter Frame
10:30 a.m. Precision Ag Discussion
11:45 a.m. Cooperating Agencies (FSA, NRCS, and SWCD)
12:30 p.m. Sponsored Lunch (Participants not seeking pesticide applicator recertification or Dicamba Certification are welcome
to adjourn following lunch)
1:15 p.m. Dicamba Certification – Don Cline, BASF Crop Protection
1:45 p.m. Legal Update – Robert Christian, VDACS Pesticide Investigator
2:15 p.m. Spill Response Activity – Robbie Longest/Mike Broaddus, Extension Agents, ANR, Essex and Caroline
3:00 p.m. Wrap up paperwork and adjourn
The 2020 Four Rivers Agricultural Conference will be held Tuesday, Jan. 14 at Providence Forge Recreation Center: 9900 Carriage Rd, Providence Forge, 23140. This year’s conference will include pesticide certification training, several Specialists and Agents from Virginia Cooperative Extension that will cover a wide variety of topics, and others. In addition, you will be able to get your dicamba herbicide certification with training being offered by Don Cline of BASF. We look forward to seeing your there for a great day of learning and interaction with the experts. Lunch will be provided. Agenda detail are below.
Full Attendance to the conference has been approved for Private Pesticide Applicator Recertification in Category 90 and Commercial Categories 1A, 10, and 60. The conference has also been approved for 2.5 Virginia Nutrient Management CEU and 2.0 Contact hours for DCR Conservation Planner Re-Certification
9:00 Registration Opens/Meet with Vendors
9:35 Controlling your Drops highlighting dicamba and glyphosate– Laura Maxey-Nay, Hanover Ag Agent
10:00 Pesticide Training – droplet size/playdough- Ed Olsen, Henrico Ag Agent
10:30 Pesticide Legal Update – Robert Christian, VDACS
11:00 2nd round of registration for those not needing pesticide recertification credit
11:15 Dicamba Certification – Don Cline, BASF
12:15 Sponsored Lunch/Meet with Vendors
1:00 Agency updates
1:15 Grain Market Update- Robert Harper, Manager, Virginia Farm Bureau Grain Division
1:45 What I learned from Argentina Agriculture, pest control and nutrient management –Paul Davis
2:05 Corn Update and Hybrid Selection, Dr. Wade Thomason, Extension Grain Agronomist
2:35 Break (visit with sponsors)
2:50 Positioning Your Full-Season Soybean for Maximum Yields, Dr. David Holshouser, Extension Soybean Agronomist
3:20 Making insect management decisions now by purchasing seed for next season, Sally Taylor, Extension Grain Entomologist
3:50 Nematode Panel, various specialists will discuss current nematode control practices.
4:50 Adjourn and paperwork
The 2020 Tri-County Crop Production Conference will be held Tuesday, Jan. 14 at the Carson Volunteer Fire Department on 19806 Halifax Rd in Carson, VA. This year’s conference will host several Specialists from Virginia Tech that will cover a wide variety of topics. In addition, you will be able to get your dicamba herbicide certification with training being offered by Don Cline of BASF. We look forward to seeing your there for a great day of learning and interaction with the experts. Lunch will be provided. Agenda detail are below.
9:00 – 9:05 Welcome and Announcements
9:05 – 9:40 Positioning Your Full-Season Soybean for Maximum Yields– Dr. David Holshouser
There are many things we can do to increase full-season soybean yield, but decisions made before planting are the most important. This presentation will focus on site-specifically positioning your crop to best take advantage of the limiting resources of water, light, and nutrients.
9:40-10:20 Plant disease management – Dr. David Langston
Nematode and disease interaction issues in soybeans. Update on fungicide and seed treatments available for corn and soybeans. Common diseases occurring in 2019.
10:40 – 11:10 Update on insect pest management – Dr. Sally Taylor
Review of major insect pests in 2019. Recommendations for preparing for 2020, scouting tips to use throughout the season, and updates on insecticides available for use.
11:10 – 11:40 Small Grain and Corn Update – Dr. Wade Thomason
Review of the latest research in corn and small grain production in Virginia.
11:40 – 12:00 Getting Started with Irrigation and Irrigation Survey – Dr. Julie Shortridge
Irrigation is not used on a wide scale in Virginia. This presentation will introduce our new water specialist and a irrigation survey for growers.
12:00 -12:45 Lunch
12:45 – 1:15 Pesticides in VA update – Robert Christian, VDACS
Update on federal record keeping and worker protection standard. Additional information on changes in pesticide labeling for VA. PPE review for commonly used pesticides. Changes to paraquat labeling, handling, and training.
1:15 – 1:35 Weed control update – Scott Reiter
Roundup resistant common ragweed is common in our soybean cropping systems. There are also 4 different herbicide technology systems in play for the 2020 season. We will cover the options available and the stewardship needed to keep the herbicides on the target crops.
1:35 – 1:55 Cover crops – Mike Parrish
Cover crops have many uses in our production systems. Soil erosion control, soil health properties, weed control, and moisture retention. Presentation will cover results from local cover crop plots and impact on these properties.
1:55 – 3:00 On Target Academy – Don Cline, BASF
This session will cover the required training for using dicamba herbicide in post-emerge applications to Xtend soybeans and cotton. Applicator & recordkeeping requirements, nozzle selection and technology, buffer requirements, weather conditions, and tank mix additives will be explained in detail
Full Attendance to the conference has been approved for Private Pesticide Applicator Recertification in Commercial Categories 1A, 10, and 60.
A series of half-day workshops will be held in Maryland, Delaware and Virginia this winter for farmers interested in learning about the problems of herbicide resistant weeds and how to manage them. Hosted by University of Maryland Extension in collaboration with Virginia Tech and University of Delaware, these workshops are designed to equip farmers with the knowledge to improve weed control on their farms.
Farmers in the mid-Atlantic area are starting to see the impact of herbicide resistant weeds on their crop yields. With many problematic weeds now found throughout the region it is essential that farmers learn the key management strategies to control these weeds.
Sessions will cover integrated weed management tactics; palmer amaranth, common ragweed and marestail control strategies; and developing a weed management plan. There is no charge to attend and lunch will be provided. Pesticide (commercial and private) and CCA continuing education credits will be offered.
Workshop locations and times are listed below. Please RSVP to the respective meeting location to provide an accurate meal count.
February 25th (12 pm to 5 pm) Old Beale Sanctuary, 369 Queen Street,Tappahannock, VA 22560
To register call the Essex County Extension Office: at (804) 443-3551
February 26th (8 am to 1 pm) St. Mary’s County UME Office, 26737 Radio Station Way, Leonardtown, MD 20650. To register call the St. Mary’s County UME Office at 301-475- 4484
March 4th (8 am to 1 pm) Harrington Volunteer Fire Company, 20 Clark St, Harrington, DE 19952. To register call the UD Carvel REC, at 302-856-2585 (ext 540)
March 5th (8 am to 1 pm) Somerset Extension Office, 30730 Park Drive, Princess Anne, MD 21853. To register call the Somerset County Extension Office at 410- 651-1350
March 6th (8 am to 1 pm) Frederick County UME Office, 330 Montevue Lane, Frederick, MD 20712. To register, call the Frederick County UME Office at 301-600- 3576
March 7th (8 am to 1 pm) Chestertown Volunteer Fire Company, 211 Maple Ave, Chestertown, MD 21620. To register call the Kent County UME Office at 410-778- 1661
For more information contact Ben Beale at 301-475-4481, Michael Flessner at 540-315-2954, Matt Morris at 301-600-3578 or Mark VanGessel at 302-856-7303.
If you intend to apply Engenia, Xtendimax, or FeXapan this year, you need to complete the annual dicamba specific training requirement in addition to being a certified pesticide applicator. In Virginia, this training is conducted by the registrants (manufacturers), but can also be completed in another state including registrant training, state mandated training, and state approved training. Both in person and online training is acceptable. Training is not product specific; you do not have to take the training from the registrant of the product you apply.
Make sure to document your training.
Here are links to find a training event near you or complete online:
Please note that some some events require pre-registration.
The following links are under revision for 2019 but will be useful shortly:
Mississippi State Extension
For greater soybean yields, one of the best things that you can do is walk your fields. Many problems reveal themselves during the summer. Actions taken or not taken can be very noticeable. By walking fields, we can see what’s working and what’s not working. Certain problems can be solved, some cannot. For those that cannot be solved this year, we can do better next season by understanding why we have the problem. Therefore, a review of how to diagnose your crop will likely beneficial.
A few years ago, I published “Troubleshooting The Soybean Crop“. Although a little dated, most of the information is still good. This publication will guide you through how to go about diagnosing problems, includes a vegetative- and reproductive-stage outline with lots of photos, and also includes a sample crop scouting and diagnostic form. You can download a view a PDF copy, or contact me – I still have a few hard copies left. By following some general guidelines, one can become quite good at diagnosing problems. Below is a summary.
First, document everything! Memories tend to fade. We often forget or overlook details. You can document by taken notes (many phone apps or iPad/tablets work well for this). Make a recording. Take pictures – this is especially useful when you need help – and send those photos to others.
PRELIMINARY FACT FINDING. You can obtain plenty of information before you even get to the field. Although I call this preliminary (as if you’ve not seen the problem), you may need to go back to the office to refresh your memory of what you did. Information that can be acquired beforehand or back in the office includes:
- Cropping History
- Soil Information
- Pest Management Information
- Tillage and Other Cultural Practices
THE FIELD VISIT
- Take all materials and equipment needed (e.g., phones, paper, shovel, plastic bags, soil probes, etc.)
- Windshield/Whole Field Investigation
- Above-Ground Inspection
- Take Appropriate Plant or Soil Samples
- Equipment Check
- Interaction with Others
- Document Everything!
ANALYSIS OF DATA AND FINDINGS
- Look-Alike Symptoms
- Interacting Factors/More Than One Problem
DRAWING A CONCLUSION. Review the facts and data. Eliminate unlikely causes. Validate likely causes. You may be able to drawn a conclusion in the field, but lab analysis may be needed.
FOLLOW UP. Revisit the field. If you took corrective action, did it work? Why or why not?
This is a very rough outline of the guide. Again, if you want a hard copy of Troubleshooting The Soybean Crop, contact me. | <urn:uuid:8a7456cd-b64b-4c96-8dd6-9daef913efbb> | CC-MAIN-2023-40 | https://blogs.ext.vt.edu/ag-pest-advisory/category/pest_group/weed/ | 2023-09-28T18:04:14Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.880299 | 3,792 |
The need for cache is inevitable in the world of enterprise-level applications. There are boundless use cases with different combinations ranging from the data type specific cache to application specific cache. We have seen a wide variety of caching technology realizations from emerging technologies like Redis (in reality, it is more than a cache) to time-proven, simple DynaCache, which serves our purpose of caching at different levels.
IBM offers mainly two solutions for cache:
- IBM WebSphere DataPower XC10 Appliance
- WebSphere eXtreme Scale.
XC 10 can be considered a simplified version of the eXtreme scale, which can be used for HTTP session management, extension of DynaCache and also as a side cache for memory-intensive applications like IBM WebSphere Portal.
I was inspired by our recent successful implementation of DataPower XC 10 with DataPower XI 52 and WebSphere Portal for one of my clients, where the use case was to cache huge data objects ranging from 2 MB to 30 MB. We designed a tutorial to help with complete end-to-end to setup and implemented a use case to experience the power and ease of setup of XC 10 device.
In the tutorial, our use case will be to setup cache for a service that will connect to “OPEN WEATHER MAP API” (http://openweathermap.org/API ) to get the weather for a given city and we will cache the responses from the service. Even though this scenario might not be the appropriate caching scenario, we will use it for simple demonstration purposes.
With the introduction of firmware V 6.0 for the XI 52, the integration between XI 52 and XC 10 has become seamless. We can get the integration set up and working in a hour. In the tutorial, we will show the setup of DataPower XC10 seamless integration with XI 52. The below diagram shows the high level setup overview where XI52 will connect to open weather map API.
You can download the tutorial here XC10IntegrationWithXI52.
Please leave your comments or questions regarding the setup below.
- Enterprise Caching Solutions using IBM WebSphere DataPower SOA Appliances and IBM WebSphere eXtreme Scale http://www.redbooks.ibm.com/abstracts/sg248043.html | <urn:uuid:af162d32-d011-4d8d-ace6-db693f3c9adb> | CC-MAIN-2023-40 | https://blogs.perficient.com/2014/04/21/datapower-xc-10-seamless-integration-with-datapower-xi-52/ | 2023-09-28T16:56:07Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.876967 | 487 |
The constant cycle and movement of water between the atmosphere, various bodies of water and groundwater is called the hydrologic cycle. This complex cycle revolves around the heat from the sun and involves precipitation, condensation, percolation, transpiration, evaporation and other forces which circulate water.
Contamination can occur at many points in the hydrologic cycle. When contamination occurs as a result of residential construction practices or products, it is most commonly due to contamination of groundwater or freshwater watercourses by way of the storm water system and overland flow directly into watercourses. There are many other ways in which the hydrologic cycle can be impacted by contaminants and other pollutants and it is important to note that due to the connectivity between all elements of the hydrologic cycle, contaminants can quickly become dispersed and can impact a broad range of areas.
Storm water is water than falls to the surface but is not absorbed directly into the ground. Instead of infiltrating the surface directly, storm water typically flows along paved surfaces such as roads and driveways before entering into the storm water system. The North Shore storm water system is comprised of a series of culverts that drain surface flow from roads and other paved surfaces into pipes that ultimately discharge directly into nearby watercourses. The result of this type of system is that all of the contaminants located and deposited on these paved surfaces are carried directly into the surround watercourses and watersheds of the North Shore.
Contaminated storm water enters watercourse as non-point source pollution. Non-point source pollution is pollution that originates from a variety of sources and is not easily tracked to one specific source. In urban areas, there are many sources of this type of pollution including but not limited to: fertilizers, pathogens, sediment, vehicle emissions, oil, heavy metals and other chemicals used in the construction process. The combination of multiple sources of pollutants combined with the storm water system on the North Shore means that many different types of pollutants have the potential to enter into the surrounding watershed. The interactions between contaminants in the natural environment are not yet well known and are termed cumulative effects.
The North Shore
The North Shore is a unique environment made up of three governing municipalities (The District of North Vancouver, The City of North Vancouver and the District of West Vancouver). The North Shore is surrounded by the Coast Mountains to the North, Indian Arm to the East, Burrard Inlet to the South and Howe Sound to the West. These natural barriers mean that the North Shore is for the most part geographically isolated from other municipalities. As a result of this isolation, the watersheds on the North Shore are mainly impacted by the work that takes place within the three municipalities. | <urn:uuid:b88db4af-4d1c-47e9-afa7-aeffa51240e3> | CC-MAIN-2023-40 | https://blogs.ubc.ca/residentialconstructionwatershedhealth/hydrologic-cycle/ | 2023-09-28T17:44:31Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.957287 | 547 |
The growing competition in the office workplace is increasing daily and to remain in the game and produce with the ongoing increasing changes in the market; we must be in tip-top shape. Finance reports, deadlines, due dates, and all of these different commitments are going to play when working alongside co-workers to achieve a common goal. However, it’s strange that no one ever addresses the elephant in the room when it comes to working with a group of individuals, especially in small office workspaces. That big elephant is hygiene.
Office leaning is paramount in maintaining a healthy living space. The growing demand rising to the top causes a great deal of stress and other issues that can hurt the immune system, but one way that we as workers can minimize the time we are away from our desk is with practicing excellent hygiene every day. Benefits of having a clean office far out way the cost of poor hygiene. Below are 5 Ways Poor Office Hygiene is Killing Employee Productivity:
Table of Contents
1. Excessive absences
Nothing feels worse than waking up and having to go to work and feeling like crap! You have a report due, and a meeting, and plans for after work but you woke up feeling horrible. You crawl out of bed two get to the car, but you are so sick that you can’t even make it work that day. Although you’re very healthy a lot of the times the fact that you gave to someone else’s virus due to poor hygiene is now cause you to miss days from work to recover because as we all know to work, you have to go to work.
2. Raising Suspicions
After getting sick at work, everyone has the same thought. How did I get sick and who gave me the virus? The raising suspicions from contracting some virus from one of your co-workers could lead to team dysfunctions and not allow people to feel comfortable sharing Close Quarters with others because there are in fear that they may be the one who gave them the cold. Once you and the word spread around the office, no one wants to work with the sicko. The benefits of the office cleaning is you will not be the one targeted.
3. Poor Temperament
Another side effect of being sick is having a poor temper, which will negatively affect the person’s ability to have professional, productive conversations with their co-workers. How many times have you been speaking with someone and noticed that they were Snappy at you and disagreeable? If you were like me, you are aware that sick people have weak tempers because they are spending the majority of their energy fighting off the disease the best they can while living in discomfort.
4. Inability to Concentrate
Inability to concentrate one significant sign that someone has a cold. Whenever we are sick, our body is in fight or flight mode trying to recover, and it is hard to focus on the finance report while being an attack by viruses. The inability to concentrate is one of the leading causes of the lack of productivity in the office workspace. This is why office cleaning routines are key to healthy living.
5. Become a Chronic Issue
The last thing the scariest thing about getting sick due to poor hygiene in the workplace is feeling like it’s something that will become reoccurring if the problem isn’t solved. Having people who work with you and who are unable to wash their hands thoroughly and keep their body clean raise as many red flags and causes many people discomfort because if they continue to come around as sick as they are, there’s a high likelihood that we could develop the same chronic issues of Health as they do. These are the benefits of having a clean office in order to prevent poor hygiene from affecting your productivity. | <urn:uuid:a2725dcc-0553-45ea-b8e7-1794d22663fd> | CC-MAIN-2023-40 | https://blogsup.net/5-ways-in-which-bad-office-hygiene-reduces-employees-productivity/ | 2023-09-28T16:40:41Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.977349 | 771 |
Now that October has arrived, the beginning of the end has arrived for those of us who live in the Midwest of the United States, and we are becoming increasingly aware that the onset of severe winter weather is creeping ever closer to us like snow removal appleton wi.
Those of us who live in the Midwest of the United States are becoming increasingly aware that the onset of severe winter weather is creeping ever closer to us. Around this time of year, the development league normally starts to wind down, and the realization that harsh winter weather is approaching closer is another aspect that announces the beginning of the end of the season. When this occurs, it will signify that we have officially entered the home stretch of the season, and from that point onward, everything will be very exciting. Some landscapers and carpenters will not focus on the tree removal industry until the end of the building season in the fall like Snow removal Appleton Wi.
This is because the building season ends earlier than the fall season. Instead, they will concentrate on the building and construction sectors. This is a result of the fact that removing trees is a job that requires not just a high level of agility, but also a large amount of physical power to complete well. This is because their busiest year, which frequently coincides with the construction season and takes place sometime around the beginning of the year, is one of the primary factors contributing to this phenomenon. This event marks the beginning of the new fiscal year and heralds the new fiscal year for the budget in an official capacity.
In this sense, the capacity of the equipment used for trash disposal ought to be equivalent to that of the equipment used in the construction industry in terms of its ability to assist workers in accomplishing their responsibilities in a more timely and efficient manner. This is because the capacity of the equipment used for trash disposal should be equivalent to that of the equipment used in the construction industry.
This either enables consultants to quickly assist all railway lines without forgetting specific sites and cross routes that are made available to the public as part of the service agreement or gives them the capacity to do so. As part of the service agreement, specific sites and cross routes are made available to the public. As part of the terms of the service agreement, certain sites and cross routes will be made accessible to the general public.
The service agreement stipulates that specific sites and cross routes will be opened up to the general public and made available to them as part of the conditions of the agreement. As a direct and immediate result of this development, consultants are now in a position to provide help to all railway lines immediately. This is true regardless of the scenario. This organization is in the general populace’s best interest in any of the two possible futures, which both hold the potential to play out. | <urn:uuid:0e2bd4fd-b4f7-41f8-bc26-001fae964aec> | CC-MAIN-2023-40 | https://blogtrader.net/business/snow-removal-appleton-wi-all-about-it.html | 2023-09-28T18:46:51Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.959622 | 569 |
The music video we referenced last week from Bill Evans’ new album, In Good Company, has been released online. It’s for the album’s opening track, The Distance Between Two Points, a banjo instrumental Bill wrote with his daughter, Corey.
The tune was recorded with David Grier on guitar, Mike Marshall on mandolin, Todd Phillips on bass, and Darol Anger, Tashina Clarridge and Tristan Clarridge on fiddles.
Bill had wanted to do something of a concept video – a mini-documentary of sorts – so he enlisted the help of Sarah Fisher at Blue Lotus Films. They faced two challenges in pulling this off: creating a video for an instrumental piece, and for one that runs nearly six minutes in length.
Together they developed a storyline to accompany the music where a young Corey would resist her dad’s attempts to bring her to the music, only to find her own passion for it as a young woman. Clara Bekeny plays the young Corey, who appears as herself near the end of the video.
How’d they do? | <urn:uuid:6e5c5367-d875-4603-aa51-21be8257d214> | CC-MAIN-2023-40 | https://bluegrasstoday.com/distance-between-two-points-video/ | 2023-09-28T17:39:03Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.965012 | 230 |
A systems approach for analysis of high content screening assay data with topic modeling
BMC Bioinformatics volume 14, Article number: S11 (2013)
High Content Screening (HCS) has become an important tool for toxicity assessment, partly due to its advantage of handling multiple measurements simultaneously. This approach has provided insight and contributed to the understanding of systems biology at cellular level. To fully realize this potential, the simultaneously measured multiple endpoints from a live cell should be considered in a probabilistic relationship to assess the cell's condition to response stress from a treatment, which poses a great challenge to extract hidden knowledge and relationships from these measurements.
In this work, we applied a text mining method of Latent Dirichlet Allocation (LDA) to analyze cellular endpoints from in vitro HCS assays and related to the findings to in vivo histopathological observations. We measured multiple HCS assay endpoints for 122 drugs. Since LDA requires the data to be represented in document-term format, we first converted the continuous value of the measurements to the word frequency that can processed by the text mining tool. For each of the drugs, we generated a document for each of the 4 time points. Thus, we ended with 488 documents (drug-hour) each having different values for the 10 endpoints which are treated as words. We extracted three topics using LDA and examined these to identify diagnostic topics for 45 common drugs located in vivo experiments from the Japanese Toxicogenomics Project (TGP) observing their necrosis findings at 6 and 24 hours after treatment.
We found that assay endpoints assigned to particular topics were in concordance with the histopathology observed. Drugs showing necrosis at 6 hour were linked to severe damage events such as Steatosis, DNA Fragmentation, Mitochondrial Potential, and Lysosome Mass. DNA Damage and Apoptosis were associated with drugs causing necrosis at 24 hours, suggesting an interplay of the two pathways in these drugs. Drugs with no sign of necrosis we related to the Cell Loss and Nuclear Size assays, which is suggestive of hepatocyte regeneration.
The evidence from this study suggests that topic modeling with LDA can enable us to interpret relationships of endpoints of in vitro assays along with an in vivo histological finding, necrosis. Effectiveness of this approach may add substantially to our understanding of systems biology.
Toxicity screening is an essential step in drug development since safety concerns have been one of the main causes of bottlenecks before drug approval [1, 2]. In vitro assays, such as High Content Screening (HCS) methods, have become an important tool for safety screening. HCS has been actively evaluated for use in drug discovery due to the advantages of being high-throughput and requiring less physical material for testing.
Unlike conventional cytotoxicity assays, HCS offers the promise of understanding the biological functions underlying toxicity by simultaneously testing various cellular activities in live cells . Providing temporal and spatial measurements of relations within the cell, HCS has gained acceptance in the research community and it has been actively applied over the past decade for the assessment of drug toxicity and study of mechanisms [4–11]. This so-called systems cell biology has also generated positive effects in the drug discovery process .
HCS has notable advantages over traditional cytotoxicity assays because it measures multiple cellular endpoints simultaneously so that it captures a more complete and dynamic picture of cellular response to an insult. We hypothesized that these endpoints together indicate the cell's condition under stress responding to a treatment in a probabilistic relationship. Such a characteristic can not be accurately described by most of the common approaches such as clustering or PCA and should be modeled with a Bayesian relationship. Unfortunately, most, if not all, post-experiment analysis often involves building discriminative models that use each read-out assay (i.e., endpoint) as an independent feature. Specifically, these data analyses treat individual endpoints as independent features rather than observing their interdependencies in a probabilistic relationship . For example, O'Brien et al. reported an HCS assay based on the HepG2 cell line and paired the HCS endpoints with the conventional in vitro cytotoxicity assay in a one-to-one comparison to assess the human hepatotoxicity of the tested drugs . Likewise, Xu et al. generated eight cellular measurements in an HCS assay based on rat primary hepatocytes and employed a Boolean logical OR to indentify individual endpoints with high predictivity for clinical drug-induced liver injury . As promising as these results are, this practice does not take full advantage of interdependencies among these cellular endpoints indicated by the systems biology of the cell.
In order to best use the multi-parameter measurements of live cells that HCS assays provide, a statistical analysis method must have the capability to extract hidden knowledge and relationships from these measurements. The best way to address this issue is to adapt a systems approach that would not only model relations between endpoints, but also link such a relationship to elucidate the cellular events leading to toxicity . For this reason, we investigated a statistical model which attempts to both summarize cellular events reflected in the endpoints measured in a parallel fashion in HCS and establish a global understanding of their relations in the cell.
We used Latent Dirichlet Allocation (LDA) for topic modeling, which has primarily been applied to problems in text mining [17–22], to analyze the data from the HCS assays. LDA assumes that the expression of the HCS endpoints follow a probabilistic distribution and can be modeled by the mathematic expression of "topics" that consist of these endpoints. The topic model allows endpoints to be linked to multiple topics with different strength levels. Similarly, it builds probabilistic associations between topics and drugs, which we treat as documents containing occurrences of endpoint measurements (i.e., words). Thus, LDA acts as more than a classification or clustering approach and instead aids in the interpretation of the topics.
In this work, we built a topic model using LDA for rat primary hepatocyte-based HCS assays to investigate the relationship of the cellular level response to the drug treatment observed in this assay and the liver injury related necrosis observed in the whole animal (in vivo) study. Our study demonstrated the utility of topic modeling, including the innate properties of the assay, to interpret the HCS results and thus reach a better understanding of the toxic response. The results indicate that endpoints under significant topics corresponded to the cellular mechanisms involved in the progression of hepatocellular necrosis in vivo as well as recovery from liver injury. This proof-of-concept study demonstrates that topic modeling has the potential to model biological data beyond simply text documents to exploit the relationships of assay endpoints.
Materials and methods
A set of compounds with a wide range of known mechanisms of action was chosen to test the range of detection of the mechanistic profiling assays applying the cellular systems biology (CSB™) approach (CellCiphr® profile). Eight endpoints, Cell loss, Nuclear Size, DNA Damage, Apoptosis, Lysosomal Mass, DNA Fragmentation, Mitochondrial Potential, and Steatosis were measured simultaneously in populations of cultured rat primary hepatocytes at multiple time points to profile both the potency and specificity of the cellular toxicological responses . Briefly, rat primary hepatocytes were prepared using the method reported by Berry et al. . Cell viability obtained from this method ranged from 85% to 95%. Diluted test compound solutions were added to each well at identical final concentrations. The maximal concentration of treatment was 200 μM with 10-point titrations for each compound using a 2-fold dilution series and tested up to 48 hours. The final concentration of DMSO in each well was 1% (v/v). For all assays, cells were analyzed using an ArrayScan VTI HCS Reader in the high-resolution mode with a 10×/0.45 NA objective and a 0.63 × coupler.
In Vivo data from animal experimental study
The necrosis data used in this study was obtained from the Japanese Toxicogenomics Project (TGP). Details regarding the animal study protocol are available elsewhere [25, 26]. Briefly, male Sprague-Dawley rats were purchased from Charles River Japan, Inc. (Kanagawa, Japan). The TGP selected a set of compounds to test. Each group of animals was administered at low, middle and high doses with the concurrent control group. The maximum tolerated dose (MTD) of each compound was determined by one week dose range finding (DRF) study and set as the high dose. Low and middle doses were 1/10 and 1/3 of high dose, respectively. Animals were administered a single dose and then sacrificed at 3, 6, 9, and 24 hours after dosing. Liver samples were immediately collected from the left lateral lobe of the livers and processed through dehydration and embedded in paraffin block for slide preparation and observation of histopathology. Histopathological changes were examined at four well recognized institutions in Japan by certified pathologists. Alterations of histology were described using the standard terminology unified by "the Japan Toxicology Society of Pathology" which can be found at (http://www.nihs.go.jp/center/yougo/15.pdf).
The HCS assays included 8 endpoints (Steatosis, DNA Fragmentation, Mitochondrial Potential, Lysosome Mass, DNA Damage, Apoptosis, Cell Loss, and Nuclear Size) that were observed for 1, 6, 24, and 48 hours after treatment of 122 drugs (Additional file 1). These endpoints were measured in two plates with DNA Damage, Apoptosis, Lysosome Mass, and DNA Fragmentation at the first plate and Mitochondrial Potential and Steatosis at the second plate, while Cell Loss and Nuclear Size were measured at both plates. In order to incorporate all the assay measurements into our model, we treated Cell Loss and Nuclear Size in the second plate as two different endpoints. This resulted in 10 endpoints in total. Different dose levels were imposed which constituted a dose-response curve for each endpoint at the time of measure. We normalized each dose-response curve by its corresponding curve obtained through Dimethyl Sulfoxide (DMSO) solvent (control). The normalization step was followed by quantifying these cellular responses where area under the dose-response curve (AUC) was calculated by using a numerical integration approach. Subsequently, for each drug we produced a data table where every column represented a time point of an endpoint (left matrix in Figure 1A). Including the replicated plates for Cell Loss and Nuclear Size, 40 AUC values were obtained for each drug.
Since the topic modeling approach assumes all the entries of data are generated by a multinomial distribution, continuous AUC values were converted into integers (middle matrix in Figure 1A) by a discretization method that uses a binning approach. Entries from each column were divided into 100 bins and mapped to the corresponding integer. In this new numerical representation, each cell provided approximate information on the frequency of the corresponding column variable.
In order to observe the endpoint behavior over time, we changed the orientation of the data so that rows became the drug-hour combinations. Therefore, number of columns shrank to number of endpoints which was 10 including the replicates. This perspective provided a temporal observation which could be exploited by topic modeling. In other words, each drug-hour stood for a document and values in the corresponding row quantified the number of occurrences of endpoints (words) in that document. The analogy we carried out here allowed us to use 10 endpoints as a vocabulary and construct different profiles (documents) for every time step of each compound (right matrix in Figure 1A).
In this study, we used Latent Dirichlet Allocation (LDA) as a topic modeling tool, which is an improved version of earlier models [28, 29] and allows multiple topic assignments . LDA assumes that every document is a mixture of different topics which govern the allocation of words across documents. The model formalizes this principle by posing a multinomial distribution of topics, z, over words, i.e., z~Mult(θ) with parameter θ. To make the likelihood estimations computationally tractable, θ is assumed to follow a Dirichlet distribution which is the conjugate prior of multinomial distribution. Therefore a hyperparameter, α, is introduced and θ is sampled from Dir(α). Similarly, word distributions are also controlled by another multinomial distribution for given topics and parameters having Dirichlet distribution which takes β as another hyperparameter. For a document which has N words, this generative process can be concisely presented as follows :
Choose θ ~ Dir(α).
For each of the words w n where
Choose a topic z n ~ Mult(θ)
Choose a word w n from another multinomial distribution that is conditioned on the topic z n and a prior β. i.e., p(w n | zn,β)
A distinguishing feature of LDA is that it can assign an unseen document to discovered topics. Furthermore, it provides interpretable conditional probability tables (CPT) for aforementioned associations such as document-topic (p(topic|document)) and word-topic (p(word|topic)). CPTs not only give the mixture weights of topics for given documents, but also tell how likely it is that a word comes from a given topic.
CPTs can be used to measure the document-topic associations. These probabilistic values can also be used to rank the most probable topics. However, there is a need to measure diagnostic topics for a class of documents instead of an individual treatment. Griffiths and Steyvers introduced this term to link a class of documents to their statistically significant topic or diagnostic (indicator) topic . The methodology first requires calculation of the mean probabilities of each category for a given topic k. Secondly, each class (c) mean for topic k, , is divided by the sum of all class means for topic k. If there are C categories, the following expression gives the significance score of topic k, for a class c.
Finally, we have a C xK matrix in which rows are the scores for topics and we declare k* as the diagnostic topic for a group c if .
One of the goals in toxicogenomics is to link in vitro findings with in vivo study in order to better understand the mechanisms underlying toxic insult. Importantly, the concordance of the in vivo and in vitro results is a key indicator of potential to replace and reduce the animal uses in assessing risk of a broad range of medical and pharmaceutical products. Implementation of the model on HCS data was followed by analyzing 45 compounds whose histopathological data and HCA data available for this study, where the histopathological data was obtained from the TGP database while the HCS study was conducted by a commercial vendor (Additional file 2). We split drugs into groups based on whether they caused necrosis at 6 or 24 hour after treatment. This split resulted in three groups: 22 drugs with no necrosis finding at either time point, 15 drugs showing necrosis at 6 hours, and 13 drugs showing necrosis at 24 hours (Additional file 3). Corresponding settings in Table 1 were used to detect diagnostic topics, a concept which was originally developed for detecting topics that match with documents that share a commonality. Similarly, we extend this notion to identifying topics to observe their agreement with necrosis vs. non-necrosis findings at either 6 or 24 hours. Figure 1B illustrates how the settings below were incorporated with CPT (p(topic|drug-hour)) of 45 common drugs.
In order to see whether the model can distinguish three groups (6hr necrosis, 24hr necrosis, and non-necrosis), we set the number of topics equal to three for the vocabulary of 10 endpoints (terms). Next, using the implementation by Blei et al. , we developed the model for 488 drug-hour combinations (four time points each for the 122 compounds). The resulting conditional probability tables (CPTs) were used in three analyses: i) grouping and ranking endpoints within topics, ii) diagnostic topic identification, and iii) linking endpoints to cellular processes.
Groupings and ranking of endpoints
The topics (t) not only grouped the endpoints based on their distribution across drugs, but also provided an importance measure with the probability scores of endpoints (e) for given topics, p(e|t). More specifically, p(e|t) indicates which endpoints are more important for that particular topic. In Table 2, the endpoints for each topic are listed with the endpoints ordered based on the strength of the relation. Notice that replicated endpoints are distinguished with indices in parentheses.
Each topic contains a ranked list of 10 endpoints, but these can be separated into disjoint groups by comparing p(e|t) values. Namely, we compared three probabilities p(e|Topic 1), p(e|Topic 2), and p(e|Topic 3) for each e and assigned it to the topic with the highest probability. In doing so, we identified groups of terms with the highest association to their topics and underlined them in Table 2. Steatosis, DNA Fragmentation, Mitochodrial Potential, and Lysosome Mass were highly significant for Topic 1. Similarly, DNA Damage and Apoptosis were the most highly associated endpoint terms for Topic 2. The remaining terms, Cell Loss and Nuclear Size fell under Topic 3.
Diagnostic topics for necrosis vs. non-necrosis
The identification of diagnostic topics requires at least binary class labels so that the score can be calculated. In this case, we used histopathological data for 45 drugs generated by the TGP database to establish the Settings I, II, and III corresponding to temporal observation of necrosis and non-necrosis drugs. In each setting, necrosis observations determined two classes, i.e., necrosis vs. non-necrosis. Plugging CPTs (p(topic|drug-hour)) generated by LDA into Eq. 1, which also uses the class label, we obtained scores for each topic. In Table 3, we summarize all settings with their diagnostic topics. For instance, Setting I consistently favors Topic 1 because its score is always the greatest among the three topics. This implies that Topic 1 is the diagnostic topic for drugs causing necrosis in rats at 6 hours. Similarly, Topic 2 appears to be the diagnostic topic for the drug group associated with necrosis at 24 hours in Setting II below. On the other hand, Setting III presents a clear cut design where the classes were defined for the drugs that were never involved in necrosis at 6 and 24 hours. For the 1st hour in the non-necrosis group, Topic 1 gives the highest score. However, Topic 3 becomes the diagnostic topic for these drugs, representing an agreement between in vivo and in vitro data for non-necrosis behavior at 6 and 24 hours. Finally, Topic 3 can be claimed as the representative topic for non-necrosis drugs.
Topics as bridging components
We assigned the endpoints to topics to form disjoint clusters and determined diagnostic topics to represent drug groups for different settings. In both analyses, we used topics as auxiliary variables. By means of topics, we further linked endpoint groups from HCS data to drug groups defined in the three necrosis conditions. We followed this process to demonstrate that topics could be also used to bridge in vitro HCS data and in vivo histopatholocal findings as illustrated in Figure 2. For instance, Steatosis, DNA Fragmentation, Mitochondrial Potential, and Lysosome Mass are listed under Topic 1, which corresponds to 6th hour necrosis drugs from TGP. Drugs with necrosis appearing in the 24th hour from the in vivo study are associated with Topic 2, which contains DNA Damage and Apoptosis. Lastly, Topic 3 both indicates non-necrosis and consists of the remaining endpoints, Cell Loss and Nuclear Size. These links, finally, enable us to build transitive relationships between endpoints from the in vitro HCS data and necrosis findings in vivo.
HCS offers impressive throughput because of its parallel read outs for multiple endpoints. This approach has recently been favored as a new technology in cell systems biology [4–11] and has been demonstrated in various applications. However, this approach can further benefit from an improved bioinformatics approach, considering the interdependencies of endpoints, which is an innate property of HCS. Although methods like HCA, PCA, k-means, and SOM are commonly used to identify natural groupings of samples, topic modeling offers different aspect of results, which use conditional probabilities to highlight importance of any component we studied (time points, assay types, and endpoints). Furthermore, its probabilistic nature allows samples to be assigned to multiple clusters, even though we used these conditional probabilities to obtain mutually-exclusive endpoint clusters. A limitation of this methodology is the assumption that the data values are governed by a multinomial distribution which may not be fully appropriate for continuous data. Since a continuous probability function in such a setting is not computationally tractable, biological data were often discretized in earlier studies [32, 33]. Similarly, we have demonstrated the application of Latent Dirichlet Allocation (LDA) to HCS data.
As a proof-of-concept study, we introduced a methodology that is rooted in text mining, but by analogy could be efficiently carried out in the analysis of HCS data. Similar to the fact that a text is a mixture of topics; the measurement of endpoints for a given drug can be considered as a consequence of multiple cellular interactions. Thus, cellular responses to each compound at a particular time point were considered as a document for topic modeling. Once we applied LDA to the document-term representation for topic modeling, we obtained two probability measures in which topics played an intermediate role. That is to say, an ordered list of endpoints for given topics was generated along with topic probabilities of each drug.
In this study, topic-based probabilistic associations were interpreted in the context of necrosis findings observed by histopathological examinations from rats. In particular, necrosis was used as a criterion to determine the diagnostic topics, and drugs were categorized into those causing necrosis at 6 hours, causing necrosis at 24 hours, or not causing necrosis at either 6 or 24 hours. The purpose of this process was to match a group of cellular events caused by these groups of drugs to the progression of necrosis found in in vivo experiments. Results demonstrated a one-to-one correspondence between diagnostic topics and groups of drugs with similar necrosis profiles.
Acquisition of topics by LDA has the advantage of associating each term (endpoint) to multiple topics where they can be sorted based on probabilities. In other words, every topic consists of the same endpoints with different orders and endpoints are not forced to be assigned to a single cluster as it happens in k-means and hierarchical clustering methods. This is reasonable since none of the biological events occur independently rather in order by probabilistic significance. However, we split the endpoints into disjoint sets after showing their importance for given topics. For this reason, endpoints were assigned to their most probable topics regarding their rankings providing potentially important clues as to the cellular processes underlying a necrotic response to toxic agents. We illustrated how topics could link endpoints to a group of drugs in Figure 2 where different cellular events might be related to histopathological observations. Applying this methodology to the data here we observed the utility of the approach to interpreting HCS results.
Topic 1 was assigned as the diagnostic topic for necrosis at 6 hours, and was associated with the endpoints Steatosis, DNA Fragmentation, Mitochondrial Potential, and Lysosome Mass. Changes in DNA Fragmentation are characteristic of necrotic cell death, where the presence of 5' overhangs are seen, and changes in Lysosome Mass and Mitochondrial Potential are consistent with the changes to cell ion permeability that eventually lead to cell rupture [34, 35]. Steatosis may either be evidence of the dysregulation of cellular transport or may itself be the cause of necrosis if large amounts of lipid distort the cell to the point of rupture .
Topic 2 was associated with DNA Damage and Apoptosis, which were diagnostic for necrosis at 24 hours. The longer time after exposure reveals the difference between more and less rapid-acting compounds. These results are somewhat perplexing given the differing pathological mechanisms underlying necrosis and apoptosis, although they do share common features such as membrane potential dysregulation [36, 37]. However, it may be possible that the initial round of necrosis leads to a round of apoptosis in the remaining cells due to changes in the extracellular environment or that the length of exposure necessary to initiate the apoptotic response in those conditions is longer than the six hour time point.
Cell Loss and Nuclear Size showed a highly significant connection with Topic 3, which was an indicator of non-necrosis drugs as shown in Table 3. This could be considered as a biological confirmation of less-toxic events and indication of hepatocyte regeneration. Cell growth (increase in cell mass) and cell proliferation (increase in cell number) are usually coordinated to ensure that cell size is properly maintained. Hepatocytes are unique among differentiated parenchymal cells because they retain a stem cell-like ability to proliferate. This property remains in rat hepatocytes in primary culture and underlies the remarkable capacity of the liver to regenerate following acute injuries that diminish hepatic mass . Hepatocyte regeneration proceeds along a sequence of distinctive phases and requires priming of hepatocytes to achieve competence for proliferation, such as increasing synthesis of RNA and proteins. Thus, hepatocytes increase in size at the early stage of the cell cycle, and the change of nuclear size is proportional to the change of cellular size . Generally, the nucleus increases in size from the time of its formation . In addition, it is reported that hypertrophy precedes proliferation in liver regeneration, suggesting that the first response to liver injury is an enlargement in hepatocyte size .
All endpoints measured in the HCS assay here are essential for toxicity assessments. In that sense, besides an independent analysis or a pair-wise comparison, it is important to interpret how these events lead to toxicity. For this reason, we not only used LDA to retrieve probabilistic associations of each endpoint to topics, but also incorporated a histopathological assessment of necrosis to test whether there is any biological meaning hidden behind these topics. For example, the drugs that caused necrosis in rats after 6 hours of treatment were also observed with significant changes of in vitro measurement in some pre-lethal endpoints including Steatosis, DNA Fragmentation, Mitochondrial Potential and Lysosome Mass, while the drugs that caused necrosis after 24 hours were associated with the cellular events in DNA Damage and Apoptosis. Obviously, the former observation in the cellular assay seems to reveal more acute injury, while the latter one reflects the cell death that might correlate the necrosis in rats observed even after 24 hour treatment. In other words, our incorporation of in vivo histopathology data over time with data from HCS agreed with the conventional wisdom regarding the cause of toxic necrosis.
Although they involve different practices and meanings, in vitro and in vivo data should be considered complements of each other. One of the goals here was to make use of these two data types to reveal biological facts. Besides using a novel computational tool to analyze HCS, we provide an example of a way to efficiently bridge in vivo and in vitro data by means of topic. By using this intermediate variable, we were able to correlate histopathological findings with the results from the HCS assays. The ability of the model to discover patterns with an unsupervised nature indicates its potential to be an alternative approach for analyzing HCS data. Hence, one direct application of this methodology for us is the early detection of drug-induced liver injury by interpreting the HCS content under probabilistic measures for drugs and endpoints. We intend to apply this method to predict the DILI potential of drugs by not only considering a single endpoint, but relying on the full set of data generated by HCS.
We have presented here a systems approach that is capable of integration of multiple measurements from High Content Screening (HCS) by considering the interdependencies across endpoints. By analogy with text mining, endpoint distributions and proportions across topics were used to gain insight into the content of in vitro data. Further, discovered relations were analyzed along with corresponding in vivo data. The results showed that Latent Dirichlet Allocation (LDA) could improve the interpretation of HCS data for use in systems biology. The agreement we observed between in vitro and in vivo data through topics obtained by LDA provide early evidence for the effectiveness of this strategy.
The findings and conclusions in this article have not been formally disseminated by the US Food and Drug Administration (FDA) and should not be construed to represent the FDA determination or policy.
Watkins PB: Drug safety sciences and the bottleneck in drug development. Clin Pharmacol Ther. 2011, 89 (6): 788-790. 10.1038/clpt.2011.63.
Chen M, Vijay V, Shi Q, Liu Z, Fang H, Tong W: FDA-approved drug labeling for the study of drug-induced liver injury. Drug discovery today. 2011, 16 (15-16): 697-703. 10.1016/j.drudis.2011.05.007.
O'Brien PJ, Irwin W, Diaz D, Howard-Cofield E, Krejsa CM, Slaughter MR, Gao B, Kaludercic N, Angeline A, Bernardi P: High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity measured in a novel cell-based model using high content screening. Arch Toxicol. 2006, 80 (9): 580-604. 10.1007/s00204-006-0091-3.
Giuliano KA, Chen YT, Taylor DL: High-content screening with siRNA optimizes a cell biological approach to drug discovery: defining the role of P53 activation in the cellular response to anticancer drugs. J Biomol Screen. 2004, 9 (7): 557-568. 10.1177/1087057104265387.
Vogt A, Tamewitz A, Skoko J, Sikorski RP, Giuliano KA, Lazo JS: The benzo[c]phenanthridine alkaloid, sanguinarine, is a selective, cell-active inhibitor of mitogen-activated protein kinase phosphatase-1. J Biol Chem. 2005, 280 (19): 19078-19086. 10.1074/jbc.M501467200.
Perlman ZE, Slack MD, Feng Y, Mitchison TJ, Wu LF, Altschuler SJ: Multidimensional drug profiling by automated microscopy. Science. 2004, 306 (5699): 1194-1198. 10.1126/science.1100709.
Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM: An unbiased cell morphology-based screen for new, biologically active small molecules. PLoS Biol. 2005, 3 (5): e128-10.1371/journal.pbio.0030128.
Lovborg H, Nygren P, Larsson R: Multiparametric evaluation of apoptosis: effects of standard cytotoxic agents and the cyanoguanidine CHS 828. Mol Cancer Ther. 2004, 3 (5): 521-526.
Ghosh RN, Grove L, Lapets O: A Quantitative Cell-Based High-Content Screening Assay for the Epidermal Growth Factor Receptor-Specific Activation of Mitogen-Activated Protein Kinase. Assay and Drug Development Technologies. 2004, 2 (5): 473-481. 10.1089/adt.2004.2.473.
Milligan G: High-content assays for ligand regulation of G-protein-coupled receptors. Drug discovery today. 2003, 8 (13): 579-585. 10.1016/S1359-6446(03)02738-7.
Abraham VC, B Samson OL, Haskins JR: Automated Classification of Individual Cellular Responses Across Multiple Targets. Preclinica. 2004, 2: 349-355.
Taylor DL, Giuliano KA: Multiplexed high content screening assays create a systems cell biology approach to drug discovery. Drug Discovery Today: Technologies. 2005, 2 (2): 149-154. 10.1016/j.ddtec.2005.05.023.
Abraham VC, Taylor DL, Haskins JR: High content screening applied to large-scale cell biology. Trends in Biotechnology. 2004, 22 (1): 15-22. 10.1016/j.tibtech.2003.10.012.
Xu JJ, Henstock PV, Dunn MC, Smith AR, Chabot JR, de Graaf D: Cellular Imaging Predictions of Clinical Drug-Induced Liver Injury. Toxicological Sciences. 2008, 105 (1): 97-105. 10.1093/toxsci/kfn109.
Chen M, Zhang J, Wang Y, Liu Z, Kelly R, Zhou G, Fang H, Borlak J, Tong W: Liver Toxicity Knowledge Base (LTKB) - A Systems Approach to a Complex Endpoint. Clinical Pharmacology & Therapeutics. 2013, 95 (5): 409-412.
Blei DM, Ng AY, Jordan MI: Latent Dirichlet allocation. Journal of Machine Learning Research. 2003, 3 (4-5): 993-1022.
Bisgin H, Liu Z, Fang H, Xu X, Tong W: Mining FDA drug labels using an unsupervised learning technique--topic modeling. BMC Bioinformatics. 2011, 12 (Suppl 10): S11-10.1186/1471-2105-12-S10-S11.
Chen Y, Yin X, Li Z, Hu X, Huang JX: A LDA-based approach to promoting ranking diversity for genomics information retrieval. BMC genomics. 2012, 13 (Suppl 3): S2-
Zheng B, McLean DC, Lu X: Identifying biological concepts from a protein-related corpus with a probabilistic topic model. BMC Bioinformatics. 2006, 7: 58-10.1186/1471-2105-7-58.
Bisgin H, Liu Z, Kelly R, Fang H, Xu X, Tong W: Investigating drug repositioning opportunities in FDA drug labels through topic modeling. BMC Bioinformatics. 2012, 13 (Suppl 15): S6-10.1186/1471-2105-13-S15-S6.
He B, Tang J, Ding Y, Wang H, Sun Y, Shin JH, Chen B, Moorthy G, Qiu J, Desai P: Mining Relational Paths in Integrated Biomedical Data. PLoS ONE. 2011, 6 (12): e27506-10.1371/journal.pone.0027506.
Wang H, Ding Y, Tang J, Dong X, He B, Qiu J, Wild DJ: Finding Complex Biological Relationships in Recent PubMed Articles Using Bio-LDA. PLoS ONE. 2011, 6 (3): e17243-10.1371/journal.pone.0017243.
Giuliano KA, Gough AH, Taylor DL, Vernetti LA, Johnston PA: Early safety assessment using cellular systems biology yields insights into mechanisms of action. J Biomol Screen. 2010, 15 (7): 783-797. 10.1177/1087057110376413.
Berry N, Barritt GJ, Edwards AM: Isolated Hepatocytes: Preparation, Properties and Applications. Elsevier Science. 1991
Uehara T, Ono A, Maruyama T, Kato I, Yamada H, Ohno Y, Urushidani T: The Japanese toxicogenomics project: application of toxicogenomics. Mol Nutr Food Res. 2010, 54 (2): 218-227. 10.1002/mnfr.200900169.
Chen M, Zhang M, Borlak J, Tong W: A Decade of Toxicogenomic Research and Its Contribution to Toxicological Science. Toxicol Sci. 2012, 130 (2): 217-228. 10.1093/toxsci/kfs223.
Kodratoff Y, Catlett J: On changing continuous attributes into ordered discrete attributes. Machine Learning â€" EWSL-91. 1991, Springer Berlin Heidelberg, 482: 164-178. 10.1007/BFb0017012.
Hofmann T: Probabilistic Latent Semantic Indexing. Proceedings of the Twenty-Second Annual International SIGIR Conference on Research and Development in Information Retrieval (SIGIR-99) 1999. 1999, Berkley, CA USA, 50-57.
Deerwester S, Dumais S, Furnas G, Landauer T, Harshman R: Indexing by latent semantic analysis. Journal of the American Society for Information Science: 1990. 1990, 391-407.
Griffiths TL, Steyvers M: Finding scientific topics. Proc Natl Acad Sci USA. 2004, 101 (Suppl 1): 5228-5235.
Flaherty P, Giaever G, Kumm J, Jordan MI, Arkin AP: A latent variable model for chemogenomic profiling. Bioinformatics. 2005, 21 (15): 3286-3293. 10.1093/bioinformatics/bti515.
Liu B, Liu L, Tsykin A, Goodall GJ, Green JE, Zhu M, Kim CH, Li J: Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation. Bioinformatics. 2010, 26 (24): 3105-3111. 10.1093/bioinformatics/btq576.
Didenko VV, Ngo H, Baskin DS: Early necrotic DNA degradation: presence of blunt-ended DNA breaks, 3' and 5' overhangs in apoptosis, but only 5' overhangs in early necrosis. Am J Pathol. 2003, 162 (5): 1571-1578. 10.1016/S0002-9440(10)64291-5.
Zong WX, Thompson CB: Necrotic death as a cell fate. Genes Dev. 2006, 20 (1): 1-15. 10.1101/gad.1376506.
Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA: The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1998, 1366 (1-2): 177-196. 10.1016/S0005-2728(98)00112-1.
Edinger AL, Thompson CB: Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 2004, 16 (6): 663-669. 10.1016/j.ceb.2004.09.011.
Michalopoulos G, Cianciulli HD, Novotny AR, Kligerman AD, Strom SC, Jirtle RL: Liver regeneration studies with rat hepatocytes in primary culture. Cancer Res. 1982, 42 (11): 4673-4682.
Cohen-Fix O: Cell biology: Import and nuclear size. Nature. 2010, 468 (7323): 513-516. 10.1038/468513a.
Gregory T: Genome Size Evolution in Animals. 2005, London: Elsevier Academic Press, 1:
Miyaoka Y, Ebato K, Kato H, Arakawa S, Shimizu S, Miyajima A: Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration. Current Biology. 2012, 22 (13): 1166-1175. 10.1016/j.cub.2012.05.016.
HB is grateful to the National Center for Toxicological Research (NCTR) of U.S. Food and Drug Administration (FDA) for post-doctoral support through the Oak Ridge Institute for Science and Education (ORISE).
Publication costs of this article were funded by the US government.
This article has been published as part of BMC Bioinformatics Volume 14 Supplement 14, 2013: Proceedings of the Tenth Annual MCBIOS Conference. Discovery in a sea of data. The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/14/S14.
The authors declare that they have no competing interests.
HB performed all calculations and data analysis, and wrote the first draft of the manuscript. WT and XX had the original idea, developed the methods, and guided the data analysis and presentation of results. MC, YW, RK, and HF contributed to the data analysis, verified the calculations, and assisted with writing the manuscript. All authors read and approved the final manuscript.
About this article
Cite this article
Bisgin, H., Chen, M., Wang, Y. et al. A systems approach for analysis of high content screening assay data with topic modeling. BMC Bioinformatics 14 (Suppl 14), S11 (2013). https://doi.org/10.1186/1471-2105-14-S14-S11
- Text Mining
- Topic Modeling
- Latent Dirichlet Allocation
- Multinomial Distribution
- Nuclear Size | <urn:uuid:42d3f0d6-ccf7-4b70-ac0d-22b99af3badd> | CC-MAIN-2023-40 | https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-14-S14-S11 | 2023-09-28T16:56:44Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.9082 | 9,084 |
RF_Purify: a novel tool for comprehensive analysis of tumor-purity in methylation array data based on random forest regression
BMC Bioinformatics volume 20, Article number: 428 (2019)
With the advent of array-based techniques to measure methylation levels in primary tumor samples, systematic investigations of methylomes have widely been performed on a large number of tumor entities. Most of these approaches are not based on measuring individual cell methylation but rather the bulk tumor sample DNA, which contains a mixture of tumor cells, infiltrating immune cells and other stromal components. This raises questions about the purity of a certain tumor sample, given the varying degrees of stromal infiltration in different entities. Previous methods to infer tumor purity require or are based on the use of matching control samples which are rarely available. Here we present a novel, reference free method to quantify tumor purity, based on two Random Forest classifiers, which were trained on ABSOLUTE as well as ESTIMATE purity values from TCGA tumor samples. We subsequently apply this method to a previously published, large dataset of brain tumors, proving that these models perform well in datasets that have not been characterized with respect to tumor purity .
Using two gold standard methods to infer purity – the ABSOLUTE score based on whole genome sequencing data and the ESTIMATE score based on gene expression data- we have optimized Random Forest classifiers to predict tumor purity in entities that were contained in the TCGA project. We validated these classifiers using an independent test data set and cross-compared it to other methods which have been applied to the TCGA datasets (such as ESTIMATE and LUMP).
Using Illumina methylation array data of brain tumor entities (as published in Capper et al. (Nature 555:469-474,2018)) we applied this model to estimate tumor purity and find that subgroups of brain tumors display substantial differences in tumor purity.
Random forest- based tumor purity prediction is a well suited tool to extrapolate gold standard measures of purity to novel methylation array datasets. In contrast to other available methylation based tumor purity estimation methods, our classifiers do not need a priori knowledge about the tumor entity or matching control tissue to predict tumor purity.
Tumors represent a complex milieu that does not only comprise the malignant cells themselves but receives contributions from different cell types: Invading immune cells as a part of the hosts’ defense against the tumor, blood vessels, fibroblasts and other non-neoplastic cells constitute the tumor microenvironment. The usual procedure to investigate tumor DNA is the isolation from samples after surgical removal. Thus, the DNA which is further analyzed contains contaminating cell populations to a varying degree.
Methylation arrays such as the widely used Infinium HumanMethylation450k / MethylationEPIC array have become increasingly popular to classify tumors into clinically meaningful groups based on distinct methylation patterns [1,2,3]. The array assesses the methylation levels of mainly promoter based cytosin residues in the genome.
These unsupervised and supervised classification procedures are prone to biases coming from methylation patterns other than the ones from tumor cells, such as stromal or immune cells. Thus, it is important to filter out samples with extremely low tumor purities. In addition, when calling DMRs between samples of high versus low tumor purity, the results will be dominated by differences in tumor purity and not genuine DMRs.
In recent years, a number of methods have been published to account for this problem: The ABSOLUTE method has been developed for whole exome sequencing data and is based on measurement of allele frequencies . Unlike other subsequently published techniques which back on the use of normal samples as a reference, the method objectively measures the frequency of somatic aberrations in a specific cancer sample and relates the frequency of these to the whole DNA quantity.
The model has been developed on SNP data from a TCGA dataset which comprises 12 tumor types which have been characterized by different “omics” techniques, including also 450 K methylation arrays. (see Additional file 7: Table S3 for entity abbreviations in the TCGA dataset and the dataset derived from Capper et al.)
Although the ABSOLUTE method has been accepted as a standard for SNP data and whole genome sequencing data, its use is currently limited to samples for which either of the datasets is available. A second method, frequently used for gene expression array data, is ESTIMATE which calculates a stromal score and an immune score and combines both to infer tumor purity.
In the following, we present two Random Forest based models which permit to extrapolate both ESTIMATE and ABSOLUTE purity estimates on novel tumor methylation array datasets. Our approach differs from more recently published methods InfiniumPurify and PAMES in that it accepts the two methods (ESTIMATE and ABSOLUTE) as the gold standard for purity estimation while InfiniumPurify is based on identifying differentially methylated regions between tumor and normal samples which can be used to infer purity via a kernel density estimation. Although a control-free variant of the approach has been published recently , this is only applicable for entities which are represented in the TCGA datasets and can not be applied to e.g. entities from the pediatric spectrum which we have examined here and where no non-neoplastic tissue samples are available . Thus this method cannot be applied to study the purity in our dataset derived from Capper et al. 2018 .
PAMES (Purity Assessment from clonal Methylation Sites) builds on a number of conserved CG sites identified in the TCGA dataset to infer tumor purity . One concern about this method is that it may overrate tumor purity estimation as only few samples from the TCGA dataset reached tumor purity estimates below 0.9 which is in contrast to previous assessments of tumor purity, indicating a much wider range of tumor purities in this dataset . (Table 1).
As a general setback of all these models, to the best of our knowledge only the PAMES method has been validated outside the TCGA dataset and none of these methods has been applied in rare entities that are not represented in TCGA.
In addition, no emphasis has been laid so far on the comparison of different tumor subgroups: It has been known for several years that e.g. breast cancer and glioblastomas consist of different tumor subgroups with distinct clinical features and probably also different cells of origin. For the latter, it has even been shown that the neural subtype may be defined solely by stromal or non-neoplastic tissue contamination .
The cell of origin is particularly important when non-neoplastic controls are chosen in whole genome characterization experiments, as these samples do not represent a proper physiological control but are themselves a mixture of different non-neoplastic cell types. Our group and others have generated an extensive dataset of tumors – enriched for pediatric brain tumors- which have so far not been systematically investigated with respect to their purity. Aiming to estimate ABSOLUTE and ESTIMATE tumor purity in methlyation array data sets beyond the TCGA data set, we trained Random Forest regression models, that automatically perform selection of CpG sites important for the prediction and do not rely on supervised differentially methylation analysis between tumor versus normal tissue.
Therefore, two Random Forest models were trained, the first on the ABSOLUTE and the second on the ESTIMATE values derived from TCGA data and subsequently applied to the dataset in Capper et al. (2018, 1]. Both 450 K methylation data and ABSOLUTE values are available for in total 2310 of the TCGA samples and served as a training and test cohort for the Random Forest model. For the ESTIMATE based model, the training and test set comprised 6360 samples. We cross-compared both our ABSOLUTE and our ESTIMATE based RF models to other purity measures which were available in the TCGA dataset (such as LUMP).
Subsequently, we applied the model to the dataset published in Capper et al. (2018) to delineate tumor purities in this large set of pediatric brain tumors.
Validation of the random Forest classifier to predict tumor purity in the TCGA data
After having established two RF models as described in the methods section, we empirically compared the correlation and mean squared error of RF_Purify_ABSOLUTE/RF_Purify_ESTIMATE (Fig. 1and Additional file 1: Figure S1) with the ABSOLUTE and ESTIMATE values of different entities represented in the TCGA dataset respectively.
Overall, we found a tight correlation between either the published ABSOLUTE or ESTIMATE values and the RF predicted tumor purities. Moreover, there was no systematic bias for the new model to either over−/ or underestimate tumor purity in a given entity and no overfitting of the training data.
The global differences in purity between the different tumor types are preserved when comparing the two methods – the average tumor purity of the ESTIMATE method is higher than for the ABSOLUTE method.
To compare the RF based models with the methods of which they were derived, we went on to calculate the correlations of RF_Purify_ESTIMATE and RF_Purify_ABSOULTE with the ABSOLUTE, ESTIMATE and LUMP purities which are available for the TCGA dataset (Fig. 2): As expected, the correlations between RF_Purify_ESTIMATE and ESTIMATE as well as RF_Purify_ABSOLUTE and ABSOLUTE were high (0.88 and 0.89 respectively) but also the comparison with the LUMP method yielded a high degree of concordance (correlation coefficient: 0.73/0.74 for RF_Purify_ESTIMATE/RF_Purify_ABSOLUTE). We thus concluded that the two models were able to reliably extrapolate the ESTIMATE and ABSOLUTE tumor purity measures on our test set of TCGA samples.
Seeking to further characterize the CpG sites which are the predictors in both RF models, we analyzed the distribution of CpG sites in the genome compared to all CpG sites on the 450 k array (Fig. 3 A): There was a higher fraction of CpG sites localized to the gene body when compared to all probes on the array (0.41 in both RF models, 0.36 for all CpG sites). More importantly, we find that a higher fraction of CpG sites overlaps with tumor suppressor genes in both RF based models (Fig. 3 B, 0.06 for RF_purify_ESTIMATE and 0.058 for RF_purify_ABSOLUTE and 0.012 for all CpG sites on the array), among these are important transcription factors such as SOX1 and PAX6 in RF_purify_ABSOLUTE as well as RUNX1 and also PAX6 in RF_purify_ESTIMATE, to name a few (a full list is provided as Additional file 6: Table S2). This supports the notion that CpG sites which localize to tumor suppressor genes may be helpful in distinguishing between DNA contributed from neoplastic and non-neoplastic cells in a tumor-stroma admixture.
While correlation between the RF_models and ESTIMATE/ABSOLUTE is a helpful overall measure of quality, the absolute differences in estimated purities may in some instances be more helpful to judge if there is a high overall discrepancy between models. We therefore also compared the absolute differences in tumor purities: The median differences between RF model and the corresponding gold standard were 0.01 for ESTIMATE and 0.009 for ABSOLUTE (Additional file 3: Figure S3).
Application of the model and orthogonal validation methods to the pediatric brain tumor methylation data
Having fitted our two Random Forest regression models on the TCGA dataset, we next applied the method to the previously published dataset from Capper et al. which contains methylation array data on the most important central nervous system tumors . Although ABSOLUTE purity values based from WES or SNP array data are not available for these samples, a subset of these tumors has been characterized by gene expression arrays and we calculated ESTIMATE scores for these tumors. Thus, we used this dataset as a bona fide orthogonal validation of our RF based methods.
Using the RF_Purify approach, we did not only find relevant differences between the various tumor entities but also between subgroups of tumor entities (Fig. 4):
Notably, tumor purity was highest in Medulloblastoma among all entities examined, with the WNT-subgroup displaying the highest RF_Purify_ESTIMATE and RF_Purify_ABSOLUTE scores. Reports on tumor purity in brain tumors specifically are sparse and most studies have rather aimed at delineating spatial, genetic homogeneity in tumor biopsies . Interestingly, Atypical teratoid rhabdoid tumor (ATRT) which is a genetically homogeneous disease but often perceived as histologically heterogeneous had purities rather in the lower spectrum, which correlates with its pleomorphic, histopathological appearance. The ATRT-MYC subgroup – characterized by a higher degree of immune cell infiltration than the two other subgroups ATRT-TYR and ATRT-SHH – was found to display the lowest average purity (mean RF_Purify_ESTIMATE score: 0.837).
Grossly, glial tumors displayed a lower tumor purity than embryonal ones- although in some entities, we discovered relevant subgroup specific differences: GBM-MES exhibited the lowest tumor (mean RF_Purify_ESTIMATE score: 0.801) purity from all glioblastoma samples. This is in line with the upregulation of stromal and immune signatures which is characteristic for these tumors.
To validate the tumor predictions by the RF models, we retrieved the Affymetrix data for a subset of tumors (n = 398) and calculated ESTIMATE tumor purity scores. We found both a tight correlation of RF_Purify_ESTIMATE scores and ESTIMATE (R = 0.76) and RF_Purify_ABSOLUTE and ESTIMATE (R = 0. 75).
In this dataset, both the ESTIMATE and the RF_Purify_ESTIMATE method tended to systematically indicate a higher Tumor purity than the RF_Purify_ABSOLUTE.
Overall, the RF_Purify approach allowed for the extrapolation of the ABSOLUTE technique to methylation array datasets not covered in the TCGA projects and has provided insight into tumor purity distributions among a wide range of mostly pediatric brain tumors.
Methylation array based tumor classification is becoming more and more widely used in the clinical setting. The idea to assess tumor purity from methylation data is based on an important observation: The number of probes with intermediate methylation level is greater in tumors compared to normal samples. Many of these sites which display intermediate methylation levels are the result of tumor infiltration by non-neoplastic cells. Thus, tumor (im) purity is an important latent variable which has the potential to confound statistical analysis. While several other methods have been published (InfiniumPurify / PAMES) the majority of these rely on the use of non-neoplastic tissue as control. This approach however is error prone as in many cases no appropriate control is available and the cell of origin of many tumors is either not known or not available.
We present a Random Forest based approach to estimate tumor purity. Beyond the TCGA data, we have applied tumor purity estimation to the methylation data in Capper et al. (2018) – this is a crucial step given that the vast majority of models which are available are strongly focused on the entities represented in TCGA. Based on the quantile tables presented here (Additional file 5: Table S1), these data allow for the delineation of cut-offs per entity which are able to sort out low-purity samples. More specifically, we have shown that tumor purity not only varies with the entity chosen but in some cases (such as high grade gliomas and medulloblastomas) is also depending on the subgroup of the respective entity.
A critical caveat of the RF_Purify models is the choice of the ABSOLUTE and ESTIMATE method as gold standards. The methods that we present display high concordances with the reference methods and are thus also prone to the same systemic biases which may affect either ABSOLUTE and ESTIMATE. Thus, as a potential concern, RF_Purify may systematically fail to estimate tumor purity in tumor subtypes not covered by the TCGA data set. This concern was not justified - the high correlation of RF_Purify_ESTIMATE and ESTIMATE in the set from Capper et al. indicates that RF_Purify generalizes to other entities not covered by TCGA. As a general observation, RF_Purify_ABSOLUTE scores were lower than RF_Purify_ESTIMATE scores both in the TCGA dataset and the Capper et al. data. This reproduces a systemic difference which can also be observed in the TCGA data.
Thus it is more important to consider the calculated purity of a give sample in relation to other samples from the same tumor (sub-) group (reference values are provided in Additional file 5: Table S1) and not aim at the absolute purity value- in particular given the systematic differences between ABSOLUTE and ESTIMATE (Fig. 1, Additional file 1: Figure S1).
Beyond providing a reference to exclude low purity samples from the analyses, the identification of entities and subgroups of entities with a low tumor purity may hold the promise of identifying entities with a high number of immune cells that infiltrate tumors and ultimately to identify entities which are thus amenable for immunotherapy.
We have shown that our model can also be applied to non TCGA datasets, yielding tumor purity estimations that correlate well with purities, estimated by different techniques.
Taken together, estimated tumor purity using our model is a potential helpful sample quality measure the can be accounted for by batch adjustment methods or by including it in statistical models, for example in differential expression, proteomic analysis , or QTL screening to name a few.
We aimed at generating two separate RF models, which are able to extrapolate the gold standard ABSOLUTE and ESTIMATE methods (Additional file 2: Figure S2 shows an overview on the methodology workflow). As a first step, we downloaded the available 450 K methylation array data for all TCGA samples (https://cancergenome.nih.gov/). The raw data was subjected to the same preprocessing steps as highlighted in Capper et al. and beta values were calculated accordingly.
For deriving the training and test set to generate RF_purify_ABSOLUTE we downloaded all available ABSOLUTE values from the TCGA dataset (2308 samples) and for RF_purify_ESTIMATE we used all samples with available ESTIMATE values (6343 samples). We split each of these datasets into a training set (70% of all samples) and a test set (30% of all samples) using the function “createDatapartition” (R-library caret, v 6.0–83). For the RF_Purify_ABSOLUTE, the training set consisted of 1617 samples, for the RF_Purify_ESTIMATE of 4452 samples.
To exclude the possibility that certain entities are underrepresented in the training or test set, we checked the representation of these (Additional file 4: Figure S4) and found a proportional representation of each cancer type.
To reduce the number of predictors used for final Random Forest modelling, we applied Hartigan’s Dip test to each training set independently. This procedure identifies CpG sites which follow a multimodal distribution and is thus thought to better identify probes with intermediate levels of methylation that may stem from increased stromal infiltration in the tumor .
In previous studies investigating tumor purity, it was inferred that these CpG sites were most predictive for a non-tumor cell infiltration. We tested different numbers of predictors (top 5, 10, 20, 30% of all CpG sites) for this first step of variable reduction and executed all further steps of model generation using these different numbers of predictors: Consistently, we found that the out of bag error of the subsequently trained models was lowest when using the top 20% of CpG sites selected by Hartigan’s diptest. This also held true when comparing the diptest to choosing the top 5,10,20 and 30% CpG sites with the highest standard deviation.
After this initial step of variable reduction, a two step random forest procedure was applied to both training datasets using the randomForest function (R package: randomForest): The first RF step, performed with n = 500 trees, served to further reduce the number of CpG sites. Thereafter the predictors (CpG sites) were ranked according to the built-in importance measure of the RF function.
To optimize this preliminary model, we generated further RF_models with various numbers of CpG sites (0.1, 1, 5 and 10%), calculated the tumor purities of the training sets for each of these models and chose the model which minimized the out-of-bag error. Finally, both for the ESTIMATE and the ABSOLUTE based methods, models with numbers of 856 CpG sites proved to be the model with the lowest number of predictors used but still with a low out-of-bag error.
The second RF step thus finalized both methods. The final versions of the models are available in an R-package at https://github.com/mwsill/RFpurify.
To further characterize the CpG sites which act as predictors in the two models, we used the annotations from the R-package IlluminaHumanMethylation450kanno.ilmn12.hg19 and tested how many CpG sites which were represented in the models overlapped Promoters, Gene bodies and CpG islands. To annotate CpG sites and gene symbols, we also used this database. For quantification of the overlap with tumor suppressor genes (TSG), we downloaded a list of tumor suppressor genes from the database TSG2.0 (web page https://bioinfo.uth.edu/TSGene) and overlapped these TSG with the gene annotations derived from R-package IlluminaHumanMethylation450kanno.ilmn12.hg19.
To orthogonally validate the models in a dataset outside of TCGA, we used the methylation array data from Capper et al. which were available in house and corresponding gene expression data (AffymetrixU133 arrays) in 398 samples. For the gene expression data we calculated ESTIMATE purity scores (R-package ESTIMATE: https://bioinformatics.mdanderson.org/estimate/rpackage.html) and subsequently the mean squared error and pearson correlation coefficients between the RF_Purify_ESTIMATE and RF_Purify_ABSOLUTE purities and the ESTIMATE scores.
Availability of data and materials
The R-package for this method is available at https://github.com/mwsill/RFpurify
Differentially methylated region
Leukocyte unmethylation for purity
Quantitative trait loci
Single nucleotide polymorphism
The cancer genome atlas
Tumor suppressor gene
Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018;555(7697):469–74.
Johann PD, Erkek S, Zapatka M, Kerl K, Buchhalter I, Hovestadt V, Jones DTW, Sturm D, Hermann C, Segura Wang M, et al. Atypical Teratoid/Rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell. 2016;29(3):379–93.
Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S, et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012;22(4):425–37.
Carter SL, Cibulskis K, Helman E, McKenna A, Shen H, Zack T, Laird PW, Onofrio RC, Winckler W, Weir BA, et al. Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol. 2012;30(5):413–21.
Qin Y, Feng H, Chen M, Wu H, Zheng X. InfiniumPurify: an R package for estimating and accounting for tumor purity in cancer methylation research. Genes Dis. 2018;5(1):43–5.
Benelli M, Romagnoli D, Demichelis F. Tumor purity quantification by clonal DNA methylation signatures. Bioinformatics. 2018;34(10):1642–9.
Aran D, Sirota M, Butte AJ. Systematic pan-cancer analysis of tumour purity. Nat Commun. 2015;6:8971.
Yoshihara K, Shahmoradgoli M, Martinez E, Vegesna R, Kim H, Torres-Garcia W, Trevino V, Shen H, Laird PW, Levine DA, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.
Zhang W, Feng H, Wu H, Zheng X. Accounting for tumor purity improves cancer subtype classification from DNA methylation data. Bioinformatics. 2017;33(17):2651–7.
Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.
Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, deCarvalho AC, Lyu S, Li P, Li Y, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32(1):42–56 e46.
Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, et al. Intertumoral heterogeneity within Medulloblastoma subgroups. Cancer Cell. 2017;31(6):737–54 e736.
Zheng X, Zhao Q, Wu HJ, Li W, Wang H, Meyer CA, Qin QA, Xu H, Zang C, Jiang P, et al. MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes. Genome Biol. 2014;15(8):419.
Bao W, Yang B, Li Z, Zhou Y. LAIPT: lysine acetylation site identification with polynomial tree. Int J Mol Sci. 2019;20(1):113.
Andrews SV, Ladd-Acosta C, Feinberg AP, Hansen KD, Fallin MD. “Gap hunting” to characterize clustered probe signals in Illumina methylation array data. Epigenetics Chromatin. 2016;9:56.
PDJ was funded by a scholarship of the Heidelberg School of Oncoogy which provided personnel costs. The HSCO did not play a role in the design of the study or collection, analysis or interpretation of the data or in writing the manuscript.
Ethics approval and consent to participate
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Figure S1. Pearson correlation of the ABSOLUTE purity values and RF_Purify_ABSOLUTE for the different TCGA tumor entities (A-J) and for the whole TCGA set with ESTIMATE values available (K). (PDF 127 kb)
Figure S2. Overview on the workflow of model generation used to create the two RF based models. (PDF 685 kb)
Figure S3. Histograms show the absolute differences between the RF_purify estimated tumor purity and the ESTIMATE (a) and ABSOLUTE (b) values of the TCGA dataset. (PDF 31 kb)
Figure S4. Barplots show the representation of each TCGA entity in a) RF_purify_ESTIMATE and b) RF_purify_ABSOLUTE: Y-axis denotes the percentage of samples which belong to a certain entity as compared to the whole set. Blue bars denote the training set, grey bars the whole TCGA set for which either ESTIMATE (A) or ABSOLUTE (B) values were available. (PDF 39 kb)
Table S1. Quantiles for the tumor purities as inferred by RF_Purify_ESTIMATE and RF_Purify_ABSOLUTE. (XLSX 16 kb)
Table S2. Tumor suppressor genes which overlap with the CpG sites of RF_Purify_ESTIMATE and RF_Purify_ABSOLUTE, (XLSX 11 kb)
Table S3. Abbreviations for the entities represented in the TCGA dataset and in Capper et al. (XLSX 13 kb)
About this article
Cite this article
Johann, P.D., Jäger, N., Pfister, S.M. et al. RF_Purify: a novel tool for comprehensive analysis of tumor-purity in methylation array data based on random forest regression. BMC Bioinformatics 20, 428 (2019). https://doi.org/10.1186/s12859-019-3014-z | <urn:uuid:21b8fe47-9182-4d34-a398-c8cda8bd1fe0> | CC-MAIN-2023-40 | https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-019-3014-z | 2023-09-28T18:38:06Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.906891 | 6,634 |
Activation of macrophages by silicones: phenotype and production of oxidant metabolites
BMC Immunology volume 3, Article number: 6 (2002)
The effect of silicones on the immune function is not fully characterized. In clinical and experimental studies, immune alterations associated with silicone gel seem to be related to macrophage activation. In this work we examined in vivo, phenotypic and functional changes on peritoneal macrophages early (24 h or 48 h) and late (45 days) after the intraperitoneal (i.p.) injection of dimethylpolysiloxane (DMPS) (silicone). We studied the expression of adhesion and co-stimulatory molecules and both the spontaneous and the stimulated production of reactive oxygen intermediates and nitric oxide (NO).
The results presented here demonstrate that the fluid compound DMPS induced a persistent cell recruitment at the site of the injection. Besides, cell activation was still evident 45 days after the silicone injection: activated macrophages exhibited an increased expression of adhesion (CD54 and CD44) and co-stimulatory molecules (CD86) and an enhanced production of oxidant metabolites and NO.
Silicones induced a persistent recruitment of leukocytes at the site of the injection and macrophage activation was still evident 45 days after the injection.
Nowadays we are in permanent contact with silicones, synthetic polymers containing a repeating Si-O backbone and organic groups attached to the silicon atom . Medical-grade silicones consist primarily of dimethylpolysiloxane (DMPS) and are widely used in devices including cardiac valves, intravenous tubing, intraocular lenses, digital joint arthroplasty prostheses, breast implants, syringes, needles, baby bottle nipples and many others products . Depending upon the length of the polymer chains and the amount of cross-linking between chains medical-grade silicones can be found as fluids, gels or elastomers.
The effect of silicones on the immune function is not fully characterized. It has been shown that certain forms of silicone are immunologically active and depending upon the molecular weight and the degree of cross-linking of the polymers, silicones are potent humoral adjuvants . Several studies of the silicone-induced inflammatory response in patients and animals revealed histopathological findings instead of direct evidences of cellular activation [4–6].
The initial body's reaction to the implanted material is the inflammatory response that induces recruitment and activation of different cells . The magnitude of any inflammatory response can be related to the level of activation of macrophages. This activation occurs both in inflammatory and in adaptive immune responses, and involves phenotypic and functional changes . Criteria widely used for activation are the ability to inhibit intracellular proliferation of microorganisms, the increased production of reactive oxygen intermediates and the enhanced expression of MHC and co-stimulatory molecules [9, 10]. Recently, Naim et al. showed that silicone elastomer preadsorbed with plasma proteins activated human monocytes in vitro to secrete pro-inflammatory cytokines . Besides, silicone gels and oils activated macrophages in female A.SW mice: increased production of IL-6 and IL-1β was obtained from macrophages collected from silicone fluid- and silicone oil-treated mice when cultured with increasing amounts of lipopolysaccharide .
In this work we examined early (24 or 48 h) or late (45 days) after the intraperitoneal (i.p.) injection of the fluid compound DMPS, phenotypic and functional changes on peritoneal macrophages. We studied the expression of adhesion and co-stimulatory molecules and both the spontaneous and the stimulated production of reactive oxygen intermediates and nitric oxide (NO). The present work shows that silicones induced a persistent recruitment at the site of the injection and that cell activation was still evident 45 days after the injection. Activated macrophages exhibited an increased expression of adhesion (CD54 and CD44) and co-stimulatory (CD86) molecules and an enhanced production of oxidant metabolites and NO.
In each experiment rats (n = 4/group) were injected i.p. with 1 ml of DMPS or 1 ml of PBS (normal group). Animals were killed 45 days, 48 h or 24 h after the DMPS injection and peritoneal cells were harvested to evaluate several parameters. The cell number increased significantly in all DMPS injected rats compared with normal group (p < 0.01) with a maximum 24 h post injection (Fig. 1). Differential cell counting showed a marked increase of polymorphonuclear neutrophils 24 h and 48 h post injection (p < 0.001) and a clear increase of macrophages on day 45 (p < 0.05). Lymphocytes peaked transiently 24 h post injection.
To assess the activated phenotype of peritoneal macrophages we studied the expression of CD54, CD44 and CD11b/c adhesion molecules and CD80 and CD86 co-stimulatory molecules by flow cytometry (Table 1). For each marker, we analyzed the percentage of positive cells and the density of the expression of this marker, evaluated as the mean fluorescence intensity (MFI). As can be seen, while the percentages of CD54 and CD44 positive macrophages were similar in all groups, CD11b/c positive macrophages decreased 24 h and 48 h after DMPS injection (p < 0.001). On the other hand, the MFI increased significantly for CD54 and CD44 molecules in DMPS injected rats (p < 0.05 for both markers) whereas for the CD11b/c molecule, the MFI diminished in 24 h and 48 h groups (p < 0.001) but increased 45 days after the DMPS injection (p < 0.05). Given the low expression of CD11b/c immediately after the injection, we considered it likely that active phagocytosis of silicone could contribute to a decreased level of this marker [13, 14]. Consistent with this, a high number of clear vacuoles were observed in cytospin preparations of macrophages of the 24 h group (data not shown). No differences were observed in the expression of MHC class II molecules (data not shown). The percentage of CD80 positive macrophages decreased in 24 h and 48 h groups (p < 0.01) without differences in the MFI. For the CD86 molecule the percentage of positive macrophages was significantly higher only on day 45 (p < 0.01) but the MFI increased in all DMPS injected groups (p < 0.05).
Next we studied the production in macrophages of oxidant metabolites such as H2O2 using the probe 2,7-dichloro-dihydrofluorescein(DCFH) as described previously . The oxidation of DCFH by unstimulated or phorbol myristate acetate (PMA)-stimulated macrophages was assessed by flow cytometry; macrophages were selected and gated by light scatter characteristics and fluorescence was expressed as MFI (Fig. 2). Unstimulated macrophages obtained 48 h and 45 days after DMPS injection showed an increased MFI (p < 0.01 and p < 0.001 vs. normal, respectively). In all groups PMA stimulated an increase of the oxidative burst; however, a higher production of oxidant metabolites was observed after 45 days of DMPS injection compared with normal rats (p < 0.05).
Finally, the production of NO by purified macrophages was determined after 48 h of culture with or without LPS stimulation (Fig. 3). As can be seen unstimulated macrophages from 48 h and 45 day groups showed an increased release of NO (p < 0.01 vs. normal). While LPS stimulated the NO production in cells of the 24 h group (p < 0.01 vs. 24 h unstimulated), the production was not further enhanced in 48 h and 45 day macrophages (p=NS vs. unstimulated). The NO productions by LPS-stimulated macrophages derived from silicone-injected groups were higher than LPS-stimulated normal macrophages (p < 0.05). In addition, the NO synthesis inhibitor aminoguanidine (AG) effectively suppressed the LPS-stimulated NO release in all groups and the silicone-induced NO production in 48 h and 45 day groups (p < 0.001 vs. LPS or MEDIUM).
Inflammation represents the body's local reaction to tissue injury and with biocompatible materials this step should not be long lasting. Moreover, it has been suggested that with DMPS this phase is not prolonged because the polymer is not providing a stimulus for continued inflammation . In this study we show a persistent recruitment of leukocytes after DMPS injection in the peritoneal cavity. Besides, in peritoneal macrophages, activation markers were up-regulated and the spontaneous release of oxidant metabolites and NO was enhanced still 45 days after the injection.
In silicone breast implants, chronic inflammation seems to be the most relevant process with accumulations of lymphocytes and monocytes . Even if a silicone gel filled breast implant does not rupture, small amounts of low molecular weight fluid DMPS may permeate (bleed or sweat) out of the implant into the surrounding tissue . Hydrophobic materials such as silicone do not migrate well and are coated instead with host proteins , and within one hour elastomers are at least 70 % covered with host proteins . Apparently, recruited inflammatory cells do not respond to DMPS itself but to adsorbed, partially denatured plasma proteins such as IgG, albumin, fibronectin and complement components . It has been suggested that liposome-like structures can be formed within the body of an implant, involving water-soluble and hydrophobic constituents . When administered in vivo liposomes interact almost exclusively with the mononuclear phagocytic system and in an i.p. injection resident macrophages take up liposomes in large quantities and monocytes can be recruited from the general circulation [22, 23]. This could account for the persistent stimulation that we found in our study, after several days of DMPS in the peritoneal cavity. Perhaps the association of vesicular and lipoidal structures with host proteins could facilitate this strong stimulatory capacity. However the activity of "naked" DMPS should also be considered. Previous work support the stimulatory capacity of silicone in vitro without the influence of plasma proteins: when peritoneal macrophages are cultured on silicone-coated plates, their cytotoxic activity on cancer cells is markedly augmented and the activity of antigen presenting cell is enhanced .
The activation of macrophages is an important event involved in inflammation, T cell activation and adjuvanticity. Adhesion and co-stimulatory molecules are up-regulated with key implications on antigen presentation and T cell priming . In rats, strong stimulatory capacity for primary immune response is associated with the expression of the co-stimulatory ligands CD80 and CD86 . After DMPS injection in peritoneal macrophages the MFI for CD54, CD44 and CD86 increased significantly in all injected rats (24 h, 48 h and 45 days after injection) providing evidences of cellular activation status.
After activation, cytokines, reactive oxygen intermediates and NO that belong to the molecular repertoire of activated macrophages are up-regulated . The cytokine stimulating capacity of silicone has been already demonstrated . Macrophages layered on DMPS and silicone rubber with or without protein adsorption produce variable levels of IL-1β, IL-6 and TNF-α depending on the polymer and adsorbed protein . Moreover, chronic loading of macrophages with silicone particles derived of dialysis tubing results in augmented release of IL-1 .
Inappropriate stimulation of NADPH oxidase and NO pathways are associated with chronic inflammation. Here we showed the ability of DMPS to stimulate the production of reactive oxygen intermediates and NO up to 45 after injection. We found that silicone primed macrophages for the production of both H2O2 and NO. In fact we observed 1) enhanced production of H2O2 after PMA stimulation and 2) NO production beyond only constitutive levels present in control samples. Measurement of H2O2 by inflammatory cells adherent to the surface of silicone elastomer 2 or 7 days after the implantation has been used to evaluate biological reactions against biomaterials . On the other hand, our data are in agreement with a previous report showing that children breast fed by mothers with silicone implants have increased urinary excretion of NO metabolites and neopterine . Spontaneous NO release involves the in vivo activation of the NO synthase, as frequently observed in macrophages isolated from infected animals . Moreover, the NO production in macrophages grown on silicone in vitro is up to 60 % higher than controls .
With liposomes, the effective uptake and the initial activation of macrophages determine the prolonged stimulatory effect [22, 23, 30]. The similarities between silicone and lipid adjuvants could partly explain the results we described here. Considering the widespread exposure to silicone in the environment and the expanding use of this material in the world, basic research addressing the immunobiology of silicone will help to understand the effects of the interaction between silicone and the immune system and to define its role in health and disease.
In this work we examined early (24 or 48 h) or late (45 days) after the i.p. injection of the fluid compound DMPS, phenotypic and functional changes on rat peritoneal macrophages. We studied the expression of adhesion and co-stimulatory molecules and both the spontaneous and the stimulated production of reactive oxygen intermediates and NO. We show here that silicone induced a persistent recruitment of leukocytes at the site of the injection and that macrophage activation was still evident after 45 days of injection. Activated macrophages exhibited an increased expression of adhesion and co-stimulatory molecules and an enhanced production of oxidant metabolites and NO.
Materials and methods
8- to 12-week-old female Wistar rats were used in this study. Animals were housed and cared for at the Animal Resource Facilities, Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, in accordance with institutional guidelines.
PE-conjugated anti-rat CD11b, anti-rat CD44, anti-rat CD54, anti-rat CD80 and anti-ratCD86, and FITC-conjugated anti-rat MHC class II (IA) monoclonal antibodies were purchased from PharMingen (San Diego, CA). The isotyping control monoclonal antibodies were obtained from Sigma (MO, USA)
Silicone treatment and cell preparation
In each experiment rats were housed together and assigned to the 45 day, 48 h, 24 h and normal groups. Animals (n = 4/group) were injected i.p. with 1 ml of DMPS (viscosity (25°C) 5 centistokes, Sigma) or 1 ml of PBS (normal group). We started the treatment injecting the 45-day group; after 43 days of this injection, rats of the 48 h group received 1 ml of DMPS and 24 h later, 24 h and normal groups received 1 ml of DMPS or PBS respectively. The next day, all rats were killed by cervical dislocation, and peritoneal cells were harvested and prepared as described previously [10, 30]. Viability was assessed by Trypan blue exclusion test. Differential cell counting was assessed by microscopic observation of cytospin preparations stained with Giemsa. Experiments were performed two to three times.
After blocking with mouse serum, peritoneal cells were stained with conjugated mAb as described previously [10, 30]. All the staining steps were performed at 4°C in HBSS containing 5 mM EDTA and 1 % bovine serum albumin. After extensive washing cells were treated with 2% formaldehyde-PBS and 10.000 events per sample were analyzed using a Cytoron Absolute cytometer (Ortho Diagnostic System, Raritan, NJ). Debris was gated out on the basis of low forward scatter and low side angle scatter. Macrophages were selected and gated by light scatter characteristics.
DCFH oxidation assay by flow cytometry
Peritoneal cells (2 × 106 cells/ml) were loaded with 2,7-dichloro-dihydrofluorescein (DCFH, Sigma) (1 mM final concentration) in a water bath in the dark (15 min., 37°C). Loaded cells were incubated with or without phorbol myristate acetate (PMA, Sigma) for 15 min at 37°C . After the incubation, tubes were placed on ice and green fluorescence was measured on a Cytoron Absolute cytometer (Ortho Diagnostic System, Raritan, NJ).
Measurement of NO production
Peritoneal cells were washed twice, diluted with RPMI-5% heat-inactivated calf serum, plated in 96-well tissue culture plates (1 × 106 cells/well) and incubated for 2 h at 37°C. Non-adherent cells were removed by extensive washing with RPMI and adherent cells were cultured with medium alone, medium containing 1 mM aminoguanidine (AG, Sigma) to inhibit the NO synthase activity , medium with LPS (1 μg/ml, Sigma) or LPS (1 μg/ml) plus 1 mM aminoguanidine. After 48 h supernatants were collected and NO was measured as nitrite using the Griess reagent by a microplate assay .
Statistical analysis included descriptive statistics, Mann Whitney U-test, ANOVA test and Student-Neuman-Keuls post test comparisons.
Lane TH, Burns SA: Silica, silicon, and silicone...unraveling the mystery. Curr Top Microbiol Immunol. 1996, 210: 3-19.
Naim JO, Lanzafame RJ, van Oss CJ: The adjuvant effect of silicone-gel on antibody formation in rats. Immuno Investi. 1993, 22: 151-161.
Naim JO, Ippolito KML, van Oss CJ: Adjuvancy effects of different types of silicone gel. J Biomed Materi Res. 1997, 37: 534-547. 10.1002/(SICI)1097-4636(19971215)37:4<534::AID-JBM12>3.0.CO;2-8.
Sanchez-Guerrero J, Schur PH, Sergent JS, Liang MH: Silicone breast implants and rheumatic disease. Clinical, immunologic, and epidemiologic studies. Arthritis Rheum. 1994, 37: 158-168.
Yoshida SH, Swan S, Teuber SS, Gershiwn ME: Silicone breast implants: immunotoxic and epidemiologic issues. Life Sci. 1995, 56: 1299-1310. 10.1016/0024-3205(95)00081-X.
Abbondanzo SL, Young VL, Wei MQ, Miller FW: Silicone gel-filled breast and testicular implant capsules: a histologic and immunophenotypic study. Mod Pathol. 1999, 12: 706-713.
Andersson JM: Inflammatory response to implants. ASAIO Trans. 1988, 34: 101-107.
Goerdt S, Orfanos CE: Other functions, other genes: alternative activation of antigen-presenting cells. Immunity. 1999, 10: 137-142.
Grau V, Scriba A, Stehling O, Steininger B: Monocytes in the rat. Immunobiology. 2000, 202: 94-103.
Iribarren P, Correa SG, Riera CM: Induction of autoimmune prostatitis using liposomes is associated to peritoneal cells activation. Am J Reprod Immunol. 1997, 38: 343-349.
Naim JO, van Oss CJ, Ippolito KML, Zhang JW, Jin LP, Fortuna R, Buehner NA: In vitro activation of human monocytes by silicones. Colloids Surfaces B Biointerfaces. 1998, 11: 79-86. 10.1016/S0927-7765(98)00023-X.
Naim JO, Satoh M, Buehner NA, Ippolito KM, Yoshida H, Nusz D, Kurtelawicz L, Cramer SF, Reeves WH: Induction of hypergammaglobulinemia and macrophage activation by silicone gels and oils in female A.SW mice. Clin Diagn Lab Immunol. 2000, 7: 366-370. 10.1128/CDLI.7.3.366-370.2000.
Kereveur A, McIlroy D, Samri A, Oksenhendeler E, Clauvel JP, Autran B: Up-regulation of adhesion and MHC molecules on splenic monocyte/Mφ in adult haemophagocytic syndrome. Br J Haematol. 1999, 104: 871-877. 10.1046/j.1365-2141.1999.01247.x.
Spittler A, Winkler S, Gotzinger P, Oehler R, Willheim M, Tempfer C, Weigel G, Fugger R, Boltz-Nitulescu G, Roth E: Influence of glutamine on the phenotype and function of human monocytes. Blood. 1995, 86: 1564-1569.
Sterner-Kock A, Braun RK, van der Vliet A, Schrenzel MD, McDonald RJ, Kabbur MB, Vulliet PR, Hyde DM: Substance P primes the formation of hydrogen peroxide and nitric oxide in human neutrophils. J Leukoc Biol. 1999, 65: 834-840.
Committee on the safety of silicone breast implants: Immunology of silicone. Washington DC. 1999
Barker DE, Retsky MI, Schultz S: Bleeding of silicone from bag-gel breast implants, and its clinical relation to fibrous capsule reaction. Plast Reconstr Surg. 1978, 61: 836-841.
Anderson JM, Ziats NP, Azeez A, Brunstedt MR, Stack S, Bonfield TL: Protein adsorption and macrophage activation on polydimethylsiloxane and silicone rubber. J Biomater Sci Polymed. 1995, 7: 159-169.
Butler JE, Lu EP, Navarro P, Christiansen B: The adsorption of proteins on a polydimethyl-siloxane elastomer (PEP) and their antigenic behavior. Curr Top Microbiol Immunol. 1996, 210: 75-84.
Bonfield TL, Colton E, Anderson JM: Fibroblast stimulation by monocytes cultured on protein adsorbed biomedical polymers. I. Biomer and polydimethylsiloxane. J Biomed Mater Res. 1991, 25: 165-175.
Yoshida SH, Teuber SS, German JB, Gershwin ME: Immunotoxicity of silicone: implications of oxidant balance towards adjuvant activity. Food Chem Toxicol. 1994, 32: 1089-1100. 10.1016/0278-6915(94)90150-3.
Gregoriadis G: Immunological adjuvants: a role for liposomes. Immunol Today. 1990, 11: 89-97. 10.1016/0167-5699(90)90034-7.
Fortin A, Thérien HM: Mechanism of liposome adjuvanticity: An in vivo approach. Immunobiology. 1993, 188: 316-322.
Rhie JW, Han SB, Byeon JH, Ahn ST, Kim HM: Efficient in vitro model for immunotoxicologic assessment of mammary silicone implants. Plast Reconstr Surg. 1998, 102: 73-77. 10.1097/00006534-199807000-00011.
CDamoiseaux JGM, Yagita H, Okumura K, van Breda Vriesman PJC: Co-stimulatory molecules CD80 and CD86 in the rat; tissue distribution and expression by antigen-presenting cells. J Leukoc Biol. 1998, 64: 803-809.
Bommer J, Weinreich T, Lovett DH, Bouillon R, Ritz E, Gemsa D: Particles from dialysis tubing stimulate interleukin-1 secretion by Mφ. Nephrol Dial Transplant. 1990, 5: 208-213.
Krause TJ, Robertson FM, Greco RS: Measurement of intracellular hydrogen peroxide induced by biomaterials implanted in a rodent air pouch. J Biomed Mater Res. 1993, 27: 65-69.
Levine JJ, Ilowite NT, Pettei MJ, Trachtman H: Increased urinary NO3(-) + NO2- and neopterin excretion in children breast fed by mothers with silicone breast implants: evidence for macrophage activation. J Rheumatol. 1996, 23: 1083-1087.
Beckerman KP, Rogers HW, Corbett JA, Schreiber RD, McDaniel ML, Unanue ER: Release of nitric oxide during the T cell-independent pathway of macrophage activation. J Immunol. 1993, 150: 888-895.
Correa SG, Riera CM, Iribarren P: Involvement of peritoneal dendritic cells in the induction of autoimmune prostatitis. J Autoimmun. 1997, 10: 107-113. 10.1006/jaut.1996.0118.
Corbett JA, Tilton RG, Chang K, Hason KS, Ido Y, Wang JL, Sweetland MA, Lancaster JR, Williamson JR, McDaniel ML: Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes. 1992, 41: 552-556.
Tominaga K, Saito S, Matsuura M, Funatogawa K, Matsumura H, Nakano M: Role of IFN-γ on dissociation between nitric oxide and TNF/IL-6 production by murine peritoneal cells after restimulation with bacterial lipopolysaccharide. J Leukoc Biol. 1999, 66: 974-980.
This work was supported by grants from "Consejo Nacional de Investigaciones Científicas y Técnicas" (CONICET), "Consejo de Investigaciones Científicas y Tecnológicas de la Provincia de Córdoba" (CONICOR), "Secretaría de Ciencia y Técnica de la U.N.C" (SeCyT- UNC) and FONCYT.
P. I. , S. G. C. , and C. M. R. are career investigators from CONICET.
PI and SGC contributed equally to this work. NS participated in the cell isolation and differential counting of peritoneal cells. CMR actively participated in interpretation of data, writing and revision of the manuscript. PI and SGC conceived the study, participated in its design and coordination, including interpretation of data and drafted the manuscript. All the authors read and approved the final version.
About this article
Cite this article
Iribarren, P., Correa, S.G., Sodero, N. et al. Activation of macrophages by silicones: phenotype and production of oxidant metabolites. BMC Immunol 3, 6 (2002). https://doi.org/10.1186/1471-2172-3-6
- Nitric Oxide
- Peritoneal Macrophage
- Phorbol Myristate Acetate
- Mean Fluorescence Intensity | <urn:uuid:b1a15dd3-c7d7-4d4b-9cac-5238491e16aa> | CC-MAIN-2023-40 | https://bmcimmunol.biomedcentral.com/articles/10.1186/1471-2172-3-6 | 2023-09-28T16:44:22Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.876628 | 6,155 |
Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40
BMC Neurology volume 16, Article number: 217 (2016)
Alzheimer’s disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ42 ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ42) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers.
We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer’s Disease Research Center. We tested correlations between YKL-40 and CSF Tau/Aβ42 ratio, Aβ42, tau, and phosphorylated tau (ptau181). We used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts from the most significant locus to adjust YKL-40 values and tested the differences in correlations with CSF Tau/Aβ42 ratio, Aβ42, tau, and ptau181.
We found that genetic variants on the CH13L1 locus were significantly associated with CSF YKL-40 levels, but not AD risk, age at onset, or disease progression. The most significant variant is a reported expression quantitative trait locus for CHI3L1, the gene which encodes YKL-40, and explained 12.74 % of the variance in CSF YKL-40 in our study. YKL-40 was positively correlated with ptau181 (r = 0.521) and the strength of the correlation significantly increased with the addition of genetic information (r = 0.573, p = 0.006).
CSF YKL-40 levels are likely a biomarker for AD, but we found no evidence that they are an AD endophenotype. YKL-40 levels are highly regulated by genetic variation, and by including genetic information the strength of the correlation between YKL-40 and ptau181 levels is significantly improved. Our results suggest that studies of potential biomarkers may benefit from including genetic information.
Since it has been well demonstrated that Alzheimer’s disease (AD) pathology is present long before any clinical symptoms, emphasis has been on improving identification of those in this preclinical stage [1–3]. Studies have found that the ratio of cerebrospinal fluid (CSF) tau to Aβ42 is a better predictor of AD status and cognitive decline than either of these proteins individually and improves discrimination of AD from other dementias such as vascular dementia and frontotemporal lobar degeneration [4–6]. CSF levels of tau correlate with the amount of neurodegeneration, phosphorylated tau (ptau) levels correlate with tangle pathology, and Aβ42 levels inversely correlate with the amount of plaques, which makes these ideal biomarkers for AD pathology [3, 7]. Studies have focused on targeting Aβ, tau, or both proteins as potential treatments for AD, making it necessary to find alternative biomarkers that are not being directly targeted [8–11]. CSF levels of YKL-40 are a promising biomarker for AD; they are significantly higher in individuals with AD dementia than in cognitively normal individuals . CSF YKL-40 is also associated with cortical thinning in cognitively normal individuals with low levels of CSF Aβ42 who are at risk for AD, and highly correlates with CSF ptau . YKL-40 is a secreted glycoprotein, encoded by chitinase-3-like 1 protein (CHI3L1), expressed in astrocytes and associated with neuroinflammatory response. Although the exact function of YKL-40 is unknown, it has been associated with many immune and inflammatory diseases as well as several cancers [14, 15]. Studies have shown that CSF levels of YKL-40 can be used to distinguish AD from non-AD dementia, Parkinson’s disease, dementia with Lewy bodies, and to distinguish between mild cognitive impairment (MCI) that progresses to AD vs MCI not due to AD indicating that CSF YKL-40 is not simply a marker for inflammation due to neurodegeneration but may be specific enough for AD [16, 17]. However, due to individual variability and group overlap in these CSF protein levels, further studies are necessary to find ways to improve sensitivity and specificity for AD. We hypothesized that adding genetic information may provide a means to improve specificity and sensitivity of CSF YKL-40 as a biomarker for AD.
One key feature of endophenotypes is that they have a clear genetic connection with the trait of interest, and for a biomarker to be considered an endophenotype it has to be measureable, heritable, and segregate with status. The genetic connection between endophenotypes and complex traits has been demonstrated to provide power in genetic studies to identify novel variants and inform about possible underlying biology [18, 19]. CSF levels of tau, ptau181, Aβ42 are well-established AD endophenotypes and have allowed us to identify novel variants associated not only with tau and ptau181 levels but also with AD risk, tangle pathology, and cognitive decline . Recent research suggests that neuroinflammation is not merely a by-product of neurodegeneration in AD but may play a key role in pathology . Since CSF levels of YKL-40 can distinguish between AD and non-AD MCI, perhaps the unknown function of YKL-40 in neuroinflammation is involved in the progression of pathology. If polymorphisms regulating YKL-40 also contribute to some aspect of AD such as risk, age at onset, or cognitive decline then understanding their genetic regulation can help provide insights into biological mechanisms underlying AD, and can help to determine whether YKL-40 is really involved in the pathogenesis (endophenotype) or is just a biomarker for the disease.
First we performed single variant genetic analyses of CSF levels of YKL-40 to identify single nucleotide polymorphisms (SNPs) associated with YKL-40 levels. Next we analyzed whether genome-wide significant variants from our analyses were also associated with AD risk, age at onset, or progression. Finally, we tested correlations between YKL-40 and the CSF Tau/Aβ42 ratio, Aβ42, tau, and ptau181, before and after including genetic information for YKL-40 levels, to determine if adding genetic information can improve the correlation with other known biomarkers, especially ptau181.
The Washington University Institutional Review Board approved this study. Written informed consent was obtained from participants or their family members.
All 379 individuals with measured CSF levels of YKL-40 were from the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (Knight-ADRC; Table 1). Dementia severity was determined using the Clinical Dementia Rating (CDR) where 0 indicates cognitive normality, 0.5 is defined as very mild dementia, 1 is mild dementia, 2 is moderate dementia, and 3 is severe dementia . There were 80 cases, defined as individuals with CDR > 0 at lumbar puncture, and 299 cognitively normal controls (CDR = 0 at lumbar puncture; Table 1). Neuropsychological and clinical assessments were collected for all participants and CSF was collected in the morning after an overnight fast, processed, and stored at -80 °C, as described previously . Individuals were evaluated by Clinical Core personnel at Washington University.
Genotyping and quality control
The samples were genotyped with the Illumina 610 or Omniexpress chip. Stringent quality control criteria were applied to each genotyping array separately before combining data. A ≤98 % call rate was applied for single nucleotide polymorphisms (SNPs) and individuals. SNPs not in Hardy-Weinberg equilibrium (p < 1 × 10-6) or with MAF <0.02 were excluded. X-chromosome SNPs were analyzed to verify gender identification. Pairwise genome-wide estimates of proportion identity-by-descent were used to find duplicate and related individuals which were eliminated from the analysis. Principal components were calculated using EIGENSTRAT to confirm ethnicity of each sample. Imputation was performed as described previously . Briefly, BEAGLE v3.3.1 software and the 1,000 genome data were used to impute up to 6 million SNPs. There were 5,986,883 imputed and genotyped SNPs after removing SNPs with a call rate <95 % or a BEAGLE r2 ≤ 0.3.
Analyte measurements and quality control
The Knight-ADRC Biomarker Core measured CSF levels of Aβ42, tau, and ptau181 using single-analyte enzyme-linked immunosorbent assays (ELISA) as described previously . CSF YKL-40 levels were measured using the MicroVue ELISA (Quidel) as described previously .
Log-transformed, standardized values for CSF YKL-40 levels were tested for normality using the Shapiro-Wilk test. We used R v3.2.1 to perform linear regression to determine if CSF levels of YKL-40 were influenced by age, gender, or sample batch (Additional file 1: Table S1). Age, gender, and sample batch were used as covariates to test association of YKL-40 with cognitive status. Correlations of CSF levels of YKL-40 with CSF Aβ42, tau, ptau181, and Tau/Aβ42 ratio were calculated using Pearson’s correlation.
Genetic association with CSF levels of YKL-40 were tested using an additive model in PLINK v1.9 (http://www.cog-genomics.org/plink2) . Covariates used were sample batch, age, gender, and two principal component factors for population structure. Statistical significance for single variant association was defined as p < 5 × 10-8 based on the commonly used threshold considered appropriate for the likely number of independent tests with Bonferroni correction. The threshold of p < 1 × 10-5 was defined for suggestive association. The genomic inflation factor for association with YKL-40 levels was 1, suggesting no evidence of inflation due to population stratification. SNP annotation was performed using ANNOVAR version 2015-06-17 and the NCBI Database of Single Nucleotide Polymorphisms (dbSNP) Build ID: 142 (http://www.ncbi.nlm.nih.gov/SNP) . RegulomeDB v1.1 (http://regulome.stanford.edu/index) was used to determine if SNPs of interest were potential regulatory elements. The Genotype-Tissue Expression (GTEx) Analysis Release V6, dbGaP Accession phs000424.v6.p1 (http://www.gtexportal.org) was used to determine if SNPs of interest were potential expression quantitative trait loci (eQTLs).
Disease progression was modeled as the change in CDR Sum of Boxes (CDR-SB) per year. A total of 1,646 individuals from longitudinal studies of AD patients with ≥3 clinical assessments over 1.5 years after being diagnosed with AD were included in the analysis. A mixed-model repeated measure framework was used to account for correlation between repeated measures in the same individual. Age, sex, baseline CDR, follow-up time, level of education, site, and PCs were included as covariates. The appropriate optimal variance-covariance structure that minimizes the Akaike Information Criterion for testing the null model AR1 was selected .
To estimate the proportion of variance in CSF levels of YKL-40 explained by genetic variants we used the coefficient of determination (R2) of a linear model of the log-transformed, standardized CSF protein levels and the additive reference allele counts of the top genome-wide associated SNP (rs10399931) with sample batch, age, and gender as covariates and subtracted the R2 of a linear model with the log-transformed, standardized CSF protein levels and the covariates in the null model. To adjust CSF levels of YKL-40 for genetic effect, we used studentized residuals from a linear regression model of the log-transformed, standardized protein levels and the additive reference allele counts of rs10399931. Age, gender, and sample batch were used as covariates to test association of the adjusted levels of YKL-40 with AD status. Correlations of the adjusted levels of YKL-40 with CSF Aβ42, tau, ptau181, and tau/Aβ42 ratio were determined using Pearson’s correlation (r). The R package cocor version 1.1-1 was used to compare correlations between CSF Aβ42, tau, ptau181, and tau/Aβ42 ratio and adjusted or unadjusted CSF protein levels. We reported the results using the Meng Z-test model , but the results for all models reported by cocor were comparable.
See Additional file 2: Supplementary Methods and Results for gene ontology over-representation and tissue-specific expression analyses.
CSF levels of YKL-40 in AD cases vs controls
After applying stringent quality control, our dataset contained CSF levels of YKL-40 for 379 individuals from the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (Knight-ADRC; Table 1). We used logistic regression including age, gender, and sample batch as covariates to test whether levels of YKL-40 were associated with AD status defined by CDR. Cases (defined by CDR at lumbar puncture >0) had significantly higher CSF levels of YKL-40 than controls (cases: 366.37 ± 136.48 ng/mL; controls: 290.18 ± 92.44 ng/mL; p = 0.015, β = 0.698; Additional file 3: Figure S1). We used linear regression to test if APOE genotype influenced YKL-40 and found there was no effect on YKL-40 levels (p = 0.704). Several studies indicate that CSF Tau/Aβ42 ratio is a better predictor of disease status than clinical assessment [5, 6]. We tested the correlation between CSF Tau/Aβ42 ratio and YKL-40. Levels of YKL-40 were positively correlated with CSF Tau/Aβ42 ratio (p = 2.61 × 10-8, r = 0.318), most likely due to the positive correlation with tau (p = 7.06 × 10-22, r = 0.522) since tau and Tau/Aβ42 ratio are highly correlated (p = 3.99 × 10-52, r = 0.736) and although there is a high negative correlation between Tau/Aβ42 ratio and Aβ42 levels (p = 3.07 × 10-64, r = -0.788), YKL-40 was not correlated with Aβ42 (p = 0.838, r = 0.012; Table 2 and Additional file 4: Figure S2).
Single variant analysis of CSF YKL-40 levels
To determine whether genetic variants are associated with levels of YKL-40, we used linear regression to test the additive genetic model of each single nucleotide polymorphism (SNP) for association with CSF protein levels using age, gender, sample batch, and two principal component factors for population stratification as covariates. We found 14 genome-wide significant SNPs associated with YKL-40, all in the CHI3L1 locus. The most significant SNP was rs10399931, a variant <200 bp upstream of the transcription start site for CHI3L1 (genotyped, p = 1.76 × 10-14, β = -0.575, minor allele frequency (MAF) = 0.244; Fig. 1 and Additional file 5: Table S2). We did not find any additional genome-wide significant loci when we ran the analysis conditioned on rs10399931. Data from RegulomeDB indicates that rs10399931 is likely to affect binding and gene expression; two RNA-Seq studies and the Genotype-Tissue Expression (GTEx) database have reported rs10399931 is an eQTL for CHI3L1 (whole blood: p = 1.7 × 10-11, β = -0.35; transformed fibroblasts: p = 3.1 × 10-11, β = -0.37; thyroid: p = 5.7 × 10-10, β = -0.42; lung: p = 6.7 × 10-9, β = -0.37; tibial nerve: p = 8.1 × 10-9, β = -0.33; subcutaneous adipose: p = 5.5 × 10-7, β = -0.28; tibial artery: p = 2.4 × 10-6, β = -0.26) [30, 34, 35]. CHI3L1 variants have been associated with YKL-40 levels in serum previously , but to our knowledge this is the first time it has been reported to be associated with CSF levels of YKL-40. We calculated what proportion of variance in CSF YKL-40 levels was explained by rs10399931. Age, gender, and sample batch explained 14.89 % of the variance in YKL-40 levels, and addition of the rs10399931 effect explained another 12.74 % of the variance. As a comparison, a previous GWAS study of CSF levels of tau and ptau181 estimated that the genetic effect of the genome-wide significant association located in apolipoprotein E (APOE) explained only 0.25–0.29 % of the variability of tau and ptau181 levels . Additionally, we found a signal in chromosome 13 (rs78081700, p = 6.26 × 10-8, β = 0.636, Fig. 1 and Additional file 5: Table S2) that almost reached genome-wide significance and another eight loci with suggestive p values (Fig. 1 and Additional file 5: Table S2), indicating that additional loci/genes could be associated with CSF YKL-40, although a larger sample size would be needed to confirm this hypothesis.
Association of GWAS hits and pathways with AD risk, age at onset, and disease progression
To determine if our genome-wide significant SNPs were also associated with risk for AD we searched the results from a GWAS previously published by the International Genomics of Alzheimer’s Project (I-GAP) consisting of a total 25,580 AD cases and 48,466 controls . None of our genome-wide significant SNPs had significant p-values in the I-GAP results (rs10399931: p = 0.763, β = 0.006; Table 3). Based on analyses of data from a previously published GWAS investigating genetic variants associated with age at onset for AD our genome-wide significant SNPs did not appear to be associated with age at onset (rs10399931: p = 0.197, β = 0.026; Table 3). We also found that our genome-wide significant SNPs were not significantly associated with advancement in CDR (rs10399931: p = 0.142, β = -0.072; Table 3). Recently the I-GAP published results from a study of biological pathways and gene expression networks associated with AD . None of the gene ontology terms that were enriched in our gene ontology analyses of GWAS results for YKL-40 (Additional file 6: Table S3) were found in the I-GAP report . Together these data suggest that YKL-40 may be a promising biomarker for AD, but probably not an endophenotype.
Improving CSF biomarkers and CSF YKL-40 utility by including genetic information
Because the genome-wide significant SNPs are not associated with disease status but explain a large proportion of the CSF levels of YKL-40, we hypothesized that by accounting for genetic information, it would be possible to improve the efficacy of these measures as biomarkers. Levels of YKL-40 have been reported to be correlated with CSF levels of tau and ptau181 but not Aβ42, and this was replicated in our analyses (Table 2 and Additional file 4: Figure S2) [12, 15].
We decided to focus on CSF ptau181 and YKL-40 since these were highly correlated and the results were similar for tau. First we used linear regression to determine whether rs10399931 genotype influenced ptau181 levels (p = 0.782, R2 = -0.005). Then we included the additive model for rs10399931 in YKL-40 levels and re-analyzed the correlation with ptau181. The correlation coefficient for the adjusted values of CSF YKL-40 levels and ptau181 was higher than the unadjusted values (adjusted: p = 2.82 × 10-26, r = 0.573 vs. unadjusted: p = 8.98 × 10-22, r = 0.521; Table 2). We used the R package cocor and determined that this change in correlation was statistically significant (p = 0.006, 95 % CI: -0.116, -0.020; Table 2). Similar results were found for tau (Table 2). As expected, we did not find any significant difference in the correlation between Aβ42 and the corrected or uncorrected YKL-40 values (Table 2). For CSF Tau/Aβ42 ratio, which is a powerful predictor for AD and progression, we found a marginally significant improvement when the genetic information was included (adjusted: r = 0.357 vs. unadjusted: r = 0.318; p = 0.071, 95 % CI: -0.083, 0.003, Table 2).
AD pathology is present long before any clinical symptoms [5, 21, 40–45], and multiple clinical trials are being performed in pre-symptomatic individuals. However, it is necessary to have reliable biomarkers to identify these individuals and to monitor the efficacy of new treatments. CSF ptau181 and Aβ42 have emerged as the most promising biochemical biomarkers for AD risk and progression . Although these CSF biomarker levels are highly associated with AD, there is large inter-individual variability, and a relatively large overlap in the absolute CSF levels between cases and controls. Additionally, if treatments directly target tau proteins or Aβ42, the CSF levels may no longer be an informative biomarker because the treatment could affect those levels separately from disease state. Therefore, the identification of surrogates for Aβ42 and tau and novel approaches to improve accuracy of CSF biomarkers that can control for the individual inter-variability can have a large impact on clinical trials as well as in the general practice.
CSF YKL-40 has emerged as a novel potential biomarker for AD, as it is higher in individuals with AD than in cognitively normal individuals and is highly correlated with CSF ptau181 levels [2, 12, 13, 15]. However, it is not clear whether CSF YKL-40 is simply a biomarker or also an endophenotype for AD. Biomarkers are measurable biological characteristics that can be used as indicators of complex traits, but don’t necessarily provide information about the biology of the trait. They may simply be influenced by the same biological processes rather than being part of those processes. Endophenotypes are biomarkers that are heritable traits with a genetic connection with disease, can be measured in all individuals regardless of disease status, and therefore can be highly informative about the biological causes of the disease.
In this study, we used genomic approaches to determine whether CSF YKL-40 is an endophenotype for AD, and whether CSF YKL-40 becomes more informative by adding genetic information. Here we reported for the first time a genetic analysis for CSF YKL-40 levels. We found a genome-wide significant signal on CHI3L1, which encodes YKL-40 (rs10399931: p = 1.76 × 10-14, MAF = 0.24), and multiple suggestive signals on other chromosomes. Interestingly, rs10399931 alone explains almost as much of the variance in YKL-40 levels (R2 = 0.127) as both age and gender combined (R2 = 0.149). Neither this variant or any of the suggestive variants were associated with AD risk, age at onset, or disease progression, indicating that CSF YKL-40 is probably not an endophenotype for AD.
Because of the large proportion of CSF YKL-40 variability explained by rs10399931, we analyzed whether the correlation with CSF ptau181 improves when including the genotypic information for this variant. We hypothesize that in order to use genetic information to improve biomarker efficacy, the genetic association must be strong and replicable. We also predict that the improvement of the efficacy of the biomarker could be correlated with the proportion of biomarker level variability explained by the genetic variant. Additionally, if multiple loci are significantly associated with biomarker levels, a polygenic risk score should provide better performance than single locus analyses. As hypothesized, we found a significant increase in the correlation of CSF YKL-40 with tau and ptau181 when genetic information for rs10399931 was included in the model. The correlation with the Tau/Aβ42 ratio also improved, although it did not reach statistical significance. Based on these results, we hypothesize that the addition of genotypic information could significantly increase the sensitivity and specificity of biomarkers, but strong genetic associations are needed. When multiple loci are associated with biomarker levels, genetic risk scores would probably provide better results.
Additionally, we think this approach for improving biomarker efficacy by adjusting for genetic effect would only be effective for biomarkers, as may be the case for YKL-40, and not for informative endophenotypes such as CSF levels of Aβ42 and tau. Genetic variants associated with endophenotype values are very likely to be associated with disease risk as well, as has been found previously in the case of AD endophenotypes [18, 47]. Therefore, correcting for genetic variants associated with endophenotype levels would generate a co-linearity problem and not improve, but actually worsen, the biomarker performance in that case.
Our genetic analyses indicate that although CSF YKL-40 levels are a promising biomarker for AD, there is no evidence they are an AD endophenotype. Genetic variation highly regulates CSF YKL-40 levels, and by including genetic information, the correlations with CSF tau and ptau181 levels increase. Although additional studies are needed to confirm our hypothesis, our results suggest that studies of potential biomarkers for complex traits may benefit from correction of genetic effects on biomarker levels. This could be particularly important when using biomarkers as surrogate endpoints in clinical trials.
Amyloid beta (1-42)
Clinical dementia rating
CDR Sum of Boxes
Enzyme-linked immunosorbent assay
Expression quantitative trait locus
Genome-wide association study
Charles F. and Joanne Knight Alzheimer’s Disease Research Center
Minor allele frequency
Phosphorylated tau (181)
Single nucleotide polymorphism
Tarawneh R, Head D, Allison S, Buckles V, Fagan AM, Ladenson JH, Morris JC, Holtzman DM. Cerebrospinal fluid markers of neurodegeneration and rates of brain atrophy in early Alzheimer disease. JAMA Neurol. 2015;72(6):656–65.
Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE, Roe CM, Peskind ER, Li G, Galasko DR, et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease. PLoS One. 2011;6(1):e16032.
Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease. Ann Neurol. 1999;45(3):358–68.
de Jong D, Jansen RW, Kremer BP, Verbeek MM. Cerebrospinal fluid amyloid beta42/phosphorylated tau ratio discriminates between Alzheimer's disease and vascular dementia. J Gerontol A Biol Sci Med Sci. 2006;61(7):755–8.
Harari O, Cruchaga C, Kauwe JS, Ainscough BJ, Bales K, Pickering EH, Bertelsen S, Fagan AM, Holtzman DM, Morris JC, et al. Phosphorylated tau-Abeta42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid. Biol Psychiatry. 2014;75(9):723–31.
Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid (42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007;64(3):343–9.
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.
Lansdall CJ. An effective treatment for Alzheimer’s disease must consider both amyloid and tau. Bioscience Horizons. 2014;7: hzu002 doi:10.1093/biohorizons/hzu002. published online June 17, 2014.
Gotz J, Ittner A, Ittner LM. Tau-targeted treatment strategies in Alzheimer’s disease. Br J Pharmacol. 2012;165(5):1246–59.
Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer’s disease: focused on considerations targeting Aβ and tau. Transl Neurodegener. 2012;1(1):1–12.
Wischik CM, Harrington CR, Storey JMD. Tau-aggregation inhibitor therapy for Alzheimer’s disease. Biochem Pharmacol. 2014;88(4):529–39.
Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ, Mintun MA, Peskind ER, Li G, Galasko DR, et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry. 2010;68(10):903–12.
Alcolea D, Vilaplana E, Pegueroles J, Montal V, Sanchez-Juan P, Gonzalez-Suarez A, Pozueta A, Rodriguez-Rodriguez E, Bartres-Faz D, Vidal-Pineiro D, et al. Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer’s disease. Neurobiol Aging. 2015;36(6):2018–23.
Bonneh-Barkay D, Wang G, Starkey A, Hamilton RL, Wiley CA. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. J Neuroinflammation. 2010;7:34.
Antonell A, Mansilla A, Rami L, Llado A, Iranzo A, Olives J, Balasa M, Sanchez-Valle R, Molinuevo JL. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis. 2014;42(3):901–8.
Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P, Blennow K, Kornhuber J, Maler JM, Zetterberg H, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther. 2015;7(1):74.
Wennstrom M, Surova Y, Hall S, Nilsson C, Minthon L, Hansson O, Nielsen HM. The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer's but Not Parkinson's disease or dementia with lewy bodies. PLoS One. 2015;10(8):e0135458.
Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM, Benitez BA, Jeng AT, Skorupa T, Carrell D, et al. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer’s disease. Neuron. 2013;78(2):256–68.
Cruchaga C, Kauwe JS, Nowotny P, Bales K, Pickering EH, Mayo K, Bertelsen S, Hinrichs A, Alzheimer's Disease Neuroimaging I, Fagan AM, et al. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer’s disease. Hum Mol Genet. 2012;21(20):4558–71.
Nazem A, Sankowski R, Bacher M, Al-Abed Y. Rodent models of neuroinflammation for Alzheimer’s disease. J Neuroinflammation. 2015;12:74.
Morris JC, Price JL. Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer’s disease. J Mol Neurosci. 2001;17(2):101–18.
Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, LaRossa GN, Spinner ML, Klunk WE, Mathis CA, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006;59(3):512–9.
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet. 2006;38(8):904–9.
Browning BL, Browning SR. Efficient multilocus association testing for whole genome association studies using localized haplotype clustering. Genet Epidemiol. 2007;31(5):365–75.
R Core Team: R: A language and environment for statistical computing. In. Vienna, Austria: R Foundation for Statistical Computing; 2015.
Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38(16):e164.
Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–11.
Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S, et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012;22(9):1790–7.
GTEx Consortium. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015;348(6235):648–60.
Cruchaga C, Kauwe JS, Mayo K, Spiegel N, Bertelsen S, Nowotny P, Shah AR, Abraham R, Hollingworth P, Harold D, et al. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer’s disease. PLoS Genet. 2010;6(9):e1001101.
Diedenhofen B, Musch J. cocor: a comprehensive solution for the statistical comparison of correlations. PLoS One. 2015;10(3):e0121945.
Meng XL, Rosenthal R, Rubin DB. Comparing correlated correlation-coefficients. Psychol Bull. 1992;111(1):172–5.
Veyrieras JB, Kudaravalli S, Kim SY, Dermitzakis ET, Gilad Y, Stephens M, Pritchard JK. High-resolution mapping of expression-QTLs yields insight into human gene regulation. Plos Genetics. 2008;4(10):e1000214.
Pickrell JK, Marioni JC, Pai AA, Degner JF, Engelhardt BE, Nkadori E, Veyrieras JB, Stephens M, Gilad Y, Pritchard JK. Understanding mechanisms underlying human gene expression variation with RNA sequencing. Nature. 2010;464(7289):768–72.
Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, et al. Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function. N Engl J Med. 2008;358(16):1682–91.
Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452–8.
Naj AC, Jun G, Reitz C, Kunkle BW, Perry W, Park YS, Beecham GW, Rajbhandary RA, Hamilton-Nelson KL, Wang LS, et al. Effects of multiple genetic loci on age at onset in late-onset Alzheimer disease: a genome-wide association study. JAMA Neurol. 2014;71(11):1394–404.
International Genomics of Alzheimer's Disease C. Convergent genetic and expression data implicate immunity in Alzheimer’s disease. Alzheimers Dement. 2015;11(6):658–71.
Gomez-Isla T, Price JL, McKeel Jr DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer’s disease. J Neurosci. 1996;16(14):4491–500.
Hulette CM, Welsh-Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM. Neuropathological and neuropsychological changes in “normal” aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol. 1998;57(12):1168–74.
Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001;58(9):1395–402.
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR. Neuropathologic substrate of mild cognitive impairment. Arch Neurol. 2006;63(1):38–46.
Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack Jr CR, Kaye J, Montine TJ, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92.
Aschenbrenner AJ, Balota DA, Fagan AM, Duchek JM, Benzinger TL, Morris JC. Alzheimer disease cerebrospinal fluid biomarkers moderate baseline differences and predict longitudinal change in attentional control and episodic memory composites in the adult children study. J Int Neuropsychol Soc. 2015;21(8):573–83.
Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367(9):795–804.
Kauwe JS, Cruchaga C, Bertelsen S, Mayo K, Latu W, Nowotny P, Hinrichs AL, Fagan AM, Holtzman DM, Alzheimer’s Disease Neuroimaging I, et al. Validating predicted biological effects of Alzheimer's disease associated SNPs using CSF biomarker levels. J Alzheimers Dis. 2010;21(3):833–42.
We appreciate all the patients, control subjects, and their families for their participation in or support of this study.
This work was supported by grants from the National Institutes of Health (R01-AG044546, P01-AG003991, RF1AG053303, R01-AG035083, and R01-NS085419), and the Alzheimer’s Association (NIRG-11-200110). This research was conducted while CC was a recipient of a New Investigator Award in Alzheimer’s disease from the American Federation for Aging Research. CC is a recipient of a BrightFocus Foundation Alzheimer’s Disease Research Grant (A2013359S). The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681, P01 AG03991, and P01 AG026276. Some of the samples used in this study were genotyped by the ADGC and GERAD. ADGC is supported by grants from the NIH (#U01AG032984) and GERAD from the Wellcome Trust (GR082604MA) and the Medical Research Council (G0300429).
This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders and the Departments of Neurology and Psychiatry at Washington University School of Medicine.
Availability of data and materials
The phenotypic and genetic data for the Knight-ADRC are available to qualified investigators through http://knightadrc.wustl.edu/Research/ResourceRequest.htm.
YD analyzed data and wrote the manuscript. KB and DC performed genotyping. JLD-A, YC, SB, MVF, JB, SM, BS, and BH prepared genetic data: performed imputation, cleaning, and calculated principal components. CLS, and RT measured CSF levels of YKL-40. AMF, DH, JCM, KH, and AG provided data. JDD contributed conceptually to the analysis. CC prepared manuscript and supervised the project. All authors read and approved the final version of this manuscript.
JCM reported having participated in or currently participating in clinical trials of antidementia drugs sponsored by Janssen Immunotherapy, Pfizer, Eli Lilly and Co/Avid Radiopharmaceuticals, SNIFF (Study of Nasal Insulin to Fight Forgetfulness), and A4 Study (Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease) and serving as a consultant for Lilly USA, ISIS Pharmaceuticals, and the Charles Dana Foundation. DMH reported being a cofounder of C2N Diagnostics LLC; serving on the scientific advisory boards of AstraZeneca, Genentech, Neurophage, and C2N Diagnostics; and serving as a consultant for Eli Lilly and Co. Washington University receives grants to the laboratory of DMH from the Tau Consortium, Cure Alzheimer’s Fund, the JPB Foundation, Eli Lilly and Co, Janssen, and C2N Diagnostics. AMF reported serving on the scientific advisory boards of IBL International and Roche and serving as a consultant for AbbVie and Novartis. The other co-authors reported no potential conflicts of interest.
Consent for publication
Not applicable – this manuscript does not contain any individual person’s data.
Ethics approval and consent to participate
This research was approved by the Washington University Institutional Review Board. Written informed consent was obtained from participants and their family members by the Clinical and Genetics Core of the Knight-ADRC. The approval number for the Knight-ADRC Genetics Core family studies is 201104178.
Covariate associations with CSF YKL-40. Results (p-value and adjusted R2) from regression of potentially confounding covariates: age at lumbar puncture, gender, and sample batch. Only age appeared significantly associated with CSF levels of YKL-40 (p = 1.19 × 10-18, R2 = 0.184). (DOCX 16 kb)
Supplementary Methods and Results. Methods and results for the gene ontology over-representation analyses of top SNPs from the single variant analysis of CSF YKL-40 levels. 70 genes mapped to the top SNPs (p < 1 × 10-4) were significantly enriched in human brain and pituitary tissue at all levels of specificity. Figure illustrates the different human tissues with expression data available with Benjamini-Hochberg corrected p < 0.10 in the enrichment analysis and the Table shows the results for all tissues with uncorrected p < 0.05 in at least one specificity index. The specificity index represents how specific a set of genes are to a particular tissue. (DOCX 163 kb)
Beeswarm plot of the normalized CSF YKL-40 levels in cases (defined as CDR > 0 at time of lumbar puncture) compared to controls (CDR = 0 at time of lumbar puncture). p = 0.015. (DOCX 119 kb)
Scatterplots of correlations between normalized values of CSF YKL-40 and Tau/Aβ42 ratio, levels of Aβ42, ptau181, and tau. Pearson’s correlation (r). CSF YKL-40 positively correlated with Tau/Aβ42 ratio (a), ptau181 (c), and tau (d), but was not correlated with Aβ42 (b). (DOCX 89 kb)
YKL-40 single variant analysis top loci (p < 1 × 10-5). Chr = chromosome, bp position = base pair position, SNP = rs ID for single nucleotide polymorphism, MAF = minor allele frequency (also effect allele), Gene = nearest gene. Chromosome and base pair position based on Build 37 of reference genome. (DOCX 14 kb)
Top gene ontology categories (p < 0.05) in both CPDB and PANTHER over-representation analyses of YKL-40 GWAS results (p < 1 × 10-4). GO ID = Identification number from the Gene Ontology Consortium, CPDB = Consensus Path Database, PANTHER = Protein Analysis Through Evolutionary Relationships. Thirteen gene ontology terms had p < 0.05 in both analyses. (DOCX 13 kb)
About this article
Cite this article
Deming, Y., Black, K., Carrell, D. et al. Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40. BMC Neurol 16, 217 (2016). https://doi.org/10.1186/s12883-016-0742-9
- Cerebrospinal fluid
- Alzheimer disease | <urn:uuid:78ab1a1c-10f9-4a2e-8d88-8c97e87a3d36> | CC-MAIN-2023-40 | https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0742-9 | 2023-09-28T18:16:22Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.886636 | 10,873 |
Temporal reciprocal relationships among anxiety, depression, and posttraumatic stress disorder for family surrogates from intensive care units over their first two bereavement years
BMC Psychiatry volume 23, Article number: 412 (2023)
Bereaved family surrogates from intensive care units (ICU) are at risk of comorbid anxiety, depression, and post-traumatic stress disorder (PTSD), but the temporal reciprocal relationships among them have only been examined once among veterans. This study aimed to longitudinally investigate these never-before-examined temporal reciprocal relationships for ICU family members over their first two bereavement years.
In this prospective, longitudinal, observational study, symptoms of anxiety, depression, and PTSD were assessed among 321 family surrogates of ICU decedents from 2 academically affiliated hospitals in Taiwan by the anxiety and depression subscales of the Hospital Anxiety and Depression Scale, and the Impact of Event Scale-Revised, respectively at 1, 3, 6, 13, 18, and 24 months postloss. Cross-lagged panel modeling was conducted to longitudinally examine the temporal reciprocal relationships among anxiety, depression, and PTSD.
Examined psychological-distress levels were markedly stable over the first 2 bereavement years: autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585–0.770, 0.546–0.780, and 0.440–0.780, respectively. Cross-lag coefficients showed depressive symptoms predicted PTSD symptoms in the first bereavement year, whereas PTSD symptoms predicted depressive symptoms in the second bereavement year. Anxiety symptoms predicted symptoms of depression and PTSD at 13 and 24 months postloss, whereas depressive symptoms predicted anxiety symptoms at 3 and 6 months postloss while PTSD symptoms predicted anxiety symptoms during the second bereavement year.
Different patterns of temporal relationships among symptoms of anxiety, depression, and PTSD over the first 2 bereavement years present important opportunities to target symptoms of specific psychological distress at different points during bereavement to prevent the onset, exacerbation, or maintenance of subsequent psychological distress.
Death and dying in intensive care units (ICUs) is common [1, 2] and increasing worldwide and even more so given COVID-19 deaths often occur in ICUs . The uncertain terminal trajectory of critical illness, the frightening nature of aggressive, life-prolonging care that threatens the patient’s bodily integrity , and ultimately the loved one’s frequently unexpected death predispose family members to increased risks for post-intensive care syndrome (PICS-F) during bereavement, including symptoms of anxiety [7,8,9,10,11,12,13,14,15,16], depression [7,8,9,10,11,12,13,14,15,16,17,18,19,20], and post-traumatic stress disorder (PTSD) [7, 9,10,11,12,13,14,15,16,17,18,19,20,21]. Grief reactions may reciprocally interfere with one another . Psychological distress commonly co-occurs as depression and anxiety ; depression and PTSD ; or anxiety, depression, and PTSD to synergistically impair physical and mental-health functioning [23, 24, 26, 27], survival , and treatment outcomes . Therefore, recognizing the potential of comorbid psychological distress and identifying modifiable risks precipitating their co-occurrence, trajectories, and future onset is paramount for improving psychological well-being of ICU decedents’ family members.
One potential mechanism for comorbid psychological distress is that preexisting psychological distress increases the risk of subsequent other psychological distress . Knowledge about the temporal relationships among anxiety, depression, and PTSD elucidates how comorbidity evolves and has important clinical implications for prevention or treatments/management of those types of psychological distress [30, 31]. However, only one study was found to investigate the temporal reciprocal relationships on how symptoms of anxiety, depression, and PTSD influence each other over time among war veterans . Therefore, the purpose of this study was to longitudinally determine the temporal reciprocal relationships among symptoms of anxiety, depression, and PTSD of ICU decedents’ family surrogates over their first two bereavement years to examine the potential mechanism of comorbidity of these three types of psychological distress.
Materials and methods
Study design/setting/study participants
This study is part of a longitudinal, observational study on associations between quality of end-of-life care in ICUs and family surrogates’ bereavement outcomes, including symptoms of anxiety , depression , and PTSD . Sampling strategy and characteristics of the study settings were reported [32, 33]. Family surrogates of critically ill patients at high risk of death (APACHE II scores > 20) were recruited consecutively from level III medical ICUs staffed by intensivists in two academically affiliated hospitals in Taiwan from January 2018 to March 2020 and followed through December 2021. Family surrogates were defined as those who self-identified as legally authorized to be the patient’s surrogate for his/her medical decisions. Each surrogate signed informed consent for participation and for allowing review of the patient’s medical record. This study was approved by the research ethics committee of the study site (Chang Gung Memorial Foundation, Institute Review Board, 201700343B0).
Participant demographics and preexisting comorbidities were recorded at enrollment. Surrogates were phone interviewed to assess their psychological distress at 1, 3, 6, 13, 18, and 24 months postloss to comply with the duration criterion for PTSD ≥ 1 month and to avoid measuring the anniversary effect at 12 months postloss.
Anxiety and depressive symptoms were measured by the Hospital Anxiety and Depression Scale (HADS) . Seven HADS items measure anxiety (HADS-A subscale) and depression (HADS-D subscale), respectively, and each has a total score ranging from 0 to 21.
PTSD symptoms were measured by the 22-item Impact of Event Scale-Revised (IES-R) . The IES-R cannot diagnose PTSD but acts as a screening instrument for PTSD symptoms and is widely used with ICU bereaved family members [7, 9, 11,12,13, 19,20,21]. The IES-R has three subscales: intrusion, avoidance, and hyperarousal. Each item is rated for its PTSD-related symptom-distress level during the preceding week on a 0 (not at all)-4 (extremely) Likert scale.
To examine the temporal reciprocal relationship between anxiety, depression, and PTSD longitudinally, we conducted a cross-lagged panel modeling (CLPM; also known as autoregressive cross-lagged modeling) to simultaneously assess whether the prior measure of each psychological-distress type predicts the subsequent measure of the same construct, and whether the prior measure of specific psychological distress (e.g., symptoms of PTSD) predicts the subsequent measurement of the other two psychological-distress types (e.g., symptoms of anxiety and depression) in the first two bereavement years by structural equation modeling in Mplus 8.6. CLPM is one of the most popular approaches for addressing temporal reciprocal relationships in medical research . In CLPM, two relations among constructs across time are of interest [37, 39]: the autoregressive and cross-lagged relations. The autoregression component of the CLPM indicates the extent to which the later measure of a construct is predicted by an immediate earlier measure of the same construct to provide information on the stability of that specific construct; whereas the cross-lagged component denotes to what extent the prior scores of one variable relate to subsequent scores of the other variables. The advantage of analyzing cross-lagged effects is to assess the strength of prediction among variables (cross-lag coefficients) while controlling for each variable’s immediate prior time score (autoregressive coefficients) to inform temporal precedence (or causal relationship) among constructs across time . Of note, despite the advantages of using CLPM to illustrate temporal reciprocal relationships among symptoms of anxiety, depression, and PTSD, the CLPM is criticized as unable to conclusively address the reciprocal relationships because it cannot distinguish within- and between-person sources of variance . However, the goal of modeling development processes (as within a personal growth pattern) should be kept separate from the goal of causal inference (as temporal relationships between variables). If the goal is to examine the causal inference of temporal reciprocal relationships between variables as in this study, use of traditional CLPM by estimating cross-lagged effects is still recommended . Model fit was assessed by the following fit indices: comparative fit index (CFI) > 0.90 , Tucker-Lewis index (TLI) > 0.90 , root mean square error of approximation (RMSEA) < 0.10 , and standardized root mean square residual (SRMR) < 0.10 .
Among the 353 patients who died in the ICUs, 321 family surrogates (90.9%) participated in bereavement surveys and constituted the study sample; 310, 304, 292, 278, 268, and 243 surrogates completed surveys at 1, 3, 6, 13, 18, and 24 months post-loss, respectively (Fig. 1). Detailed reasons for attrition from bereavement surveys are in Fig. 1. Patients of family surrogates who declined participation in (Table 1), skipped, or withdrew from bereavement surveys (Supplemental Table 1) did not differ by sociodemographics or clinical characteristics from patients of family surrogates who completed all assessments. Enrolled family surrogates who declined participation in (Table 2), skipped, or withdrew from bereavement surveys did not differ by sociodemographics or clinical characteristics (Supplemental Table 2) nor by prior wave of psychological distress (Supplemental Table 3) from those who completed all assessments. Characteristics of patients, the 321 study participants, and participant assessments of their psychological distress during bereavement are in Tables 1 and 2 and Supplemental Tables 3, respectively.
Longitudinal relationships between symptoms of anxiety, depression, and PTSD
The model fit the data fairly well: CFI = 0.955, TLI = 0.924, RMSEA = 0.097, and SRMR = 0.067. Analyses of the autoregressive coefficients showed that examined psychological-distress levels were markedly stable over the first 2 bereavement years (Fig. 2): autoregressive coefficients for symptoms of anxiety, depression, and PTSD were 0.585–0.770, 0.546–0.780, and 0.440–0.780, respectively.
Analyses of the cross-lagged coefficients showed symptoms of depression consistently predicted symptoms of PTSD above and beyond the autoregressive effects over the first bereavement year, but not vice versa (Fig. 2). However, an opposite relationship was shown for the second bereavement year: symptoms of PTSD consistently predicted symptoms of depression, but not vice versa. Further, symptoms of anxiety predicted symptoms of PTSD at 13 and 24 months postloss, whereas symptoms of PTSD consistently predicted symptoms of anxiety during the second bereavement year. Symptoms of PTSD and anxiety are bidirectionally related between 18 and 24 months postloss.
For the reciprocal relationships between symptoms of anxiety and depression, analyses of the cross-lagged coefficients showed that symptoms of depression only predicted symptoms of anxiety at 3 and 6 months postloss (Fig. 2), whereas symptoms of anxiety predicted symptoms of depression at 3, 13, and 24 months postloss. Symptoms of anxiety and depression are bidirectionally related between 1 and 3 months postloss.
We observed that examined psychological-distress levels were markedly stable over the first 2 bereavement years in line with a report for war veterans over their first two years post war . Further, we found different patterns of temporal relationships between symptoms of depression and PTSD over the first 2 bereavement years. Depressive symptoms shortly postloss predicted PTSD symptoms over the first bereavement year, whereas long-lasting PTSD symptoms predicted prolonged depressive symptoms beyond the first bereavement year. The latter result was supported by a report that PTSD at 1 year post war predicted depression at 2 years post war among veterans, but not vice versa. Furthermore, Glad and colleagues found that PTSD symptoms within the first bereavement year do not predict later grief, whereas beyond this first year, more pervasive PTSD symptoms predict grief at 30–32 months postloss. Both studies [25, 44] confirmed that long-lasting PTSD symptoms disrupt the normal grief process and precipitate prolonged depressive (grief) symptoms beyond the first bereavement year.
The temporal relationships among psychological-distress symptoms observed in this study can be understood through the theoretical frameworks of multidimensional grief theory, stress sensitivity, and the internalizing dimension of PTSD. Multidimensional grief theory characterizes grief reactions as adaptive or maladaptive responses across three content domains: separation distress, existential/identity distress, and circumstance-related distress [22, 45]. Separation distress is characterized by missing the deceased, sadness from persistent separation, and sorrow over the deceased’s failure to physically reunite with oneself. Losing a longstanding relationship during ICU care and starting a future without the patient trigger separation distress and predispose family surrogates to suffering depressive symptoms and separation anxiety.
Because these grief reactions typically recede over time , we draw from the theory of stress sensitivity to explain why subsequent PTSD symptoms emerge among individuals with symptoms of depression. Stress sensitivity proposes that individuals vulnerable to psychopathology may be more psychologically sensitive to stress and more susceptible to perceive stressful events as highly traumatic. Therefore, the psychological struggle among depressed family surrogates shortly after the death of their loved one may sensitize them to heightened negative responses towards proximal stressors during bereavement like loss reminders (i.e., cues that evoke memories of the deceased, their eternal absence) and traumatic memories of the ICU-care experience . Sensitization to bereavement stressors may explain PTSD symptoms ensuing from depressive symptoms over the first bereavement year.
These PTSD symptoms may remain stable during bereavement due to maladaptive manifestations of separation distress [22, 45]. Separation distress has been theorized to manifest from loss reminders and to be exacerbated by maladaptive coping with loss reminders . As an example of maladaptive coping, excessive behavioral or cognitive avoidance of loss reminders can interfere with remembering, reminiscing, and accepting the reality of the patient’s death , leading to long-lasting PTSD symptoms beyond the first bereavement year.
Co-occurrence of PTSD with major depressive and anxiety disorders has been explained by the internalizing dimension of PTSD . Internalized trauma may also explain why PTSD symptoms precede subsequent anxiety and depressive symptoms in the second bereavement year. When bereaved family surrogates suffer from long-lasting PTSD symptoms, they may internalize their traumatic bereavement to manifest the existential/identity distress proposed by multidimensional grief theory [22, 45]. In other words, they may feel excessive guilt about the death, blame themselves for the occurrence of the death (self-denigration), and may not find meaning in the patient’s death, leading to negative beliefs about themselves, hopelessness, despair, a sense of a future blighted by the death, or a disparaged worldview [22, 45]. Therefore, when bereaved family surrogates internalize their long-lasting PTSD symptoms, they may suffer prolonged depressive symptoms subsequently in the second bereavement year. The same speculation can be applied to the associations between the prior wave of PTSD symptoms with subsequent heighted anxiety symptoms (e.g., like distress, disgust, and anger) in the second bereavement year.
We found that symptoms of anxiety in the prior wave of assessment consistently predicted symptoms of depression and PTSD at the first and second anniversary of bereavement (Fig. 2). For bereaved with anxiety symptoms , loss reminders as the anniversary of the patient’s death approached may evoke circumstance-related distress, or intrusive distressing memories of the traumatic circumstances under which their loved one died [22, 45]. Marked avoidance of such distressing intrusive memories of the loss may be elicited. Circumstance-related distress also involves feelings of helplessness, guilt, regret, or anger over not being able to save their loved one at the time of his/her death or the horrific circumstances under which the patient died. Exposure to loss reminders near the anniversary of the patient’s death also evokes bereaved caregivers’ separation distress [22, 45] to trigger their depressive symptoms as previously discussed. Therefore, bereaved family surrogates who had higher symptoms of anxiety in the prior wave of assessment suffered higher depressive and PTSD symptoms in the subsequent anniversary of bereavement.
Symptoms of depression in the prior wave of assessment predicted symptoms of anxiety at both 3 and 6 months postloss during the first bereavement year, whereas symptoms of anxiety predicted symptoms of depression at 3 months postloss only. Therefore, a bidirectional relationship between symptoms of anxiety and depression was observed between 1 and 3 months postloss. Our results confirmed the conclusion from a meta-analysis that anxiety and depression are bidirectional risk factors for one another at early bereavement. Furthermore, symptoms of depression at 3 months postloss continuously predicted symptoms of anxiety at 6 months postloss. As previously highlighted, the psychological struggle among depressed family surrogates shortly after the death of their loved one may sensitize them to a wide range of negative emotional responses like fear, distress, disgust, and anger toward the patient’s dying process and the permanent separation from their beloved, thereby suffering heighted symptoms of anxiety.
Several limitations of our study are acknowledged. Whether our findings can be generalized to (inter)national populations beyond the sampled hospitals, family surrogates of ICU patients who died within 3 days of admission, or family surrogates who did not participate in or withdrew from bereavement surveys warrants further validation. Measuring symptoms of anxiety, depression, and PTSD by screening rather than diagnostic tools likely overestimates bereaved family surrogates’ psychological distress but avoids overlooking their need for emotional support. Factors that are associated with, mediate, or moderate the interrelationships between symptoms of anxiety, depression, and PTSD have not yet been explored. Further investigation is warranted.
Symptoms of anxiety, depression, and PTSD are highly stable over the first 2 bereavement year. Symptoms of depression shortly after the death of a loved one predict symptoms of PTSD in the first bereavement year, whereas long-lasting symptoms of PTSD interfere with the grief process leading to prolonged symptoms of anxiety and depression at the second bereavement year. Heightened anxiety symptoms in the previous wave of assessment predict symptoms of depression and PTSD at the subsequent first and second anniversaries of bereavement. With the remarkably high stability of anxiety, depression, and PTSD symptoms over the first 2 bereavement years, appearance of psychological distress shortly after the patient’s death should alert healthcare professionals to prevent persistent psychological suffering over time. Knowledge about the temporal relationships among symptoms of anxiety, depression, and PTSD has important implications for healthcare professionals working with bereaved family members of ICU decedents: targeting symptoms of specific psychological distress at different points during bereavement may prevent the development, exacerbation, or maintenance of subsequent psychological distress. This knowledge supplements our previous conclusions that improving quality of end-of-life care in ICUs might mitigate bereaved family surrogates’ symptoms of anxiety , depression , and PTSD .
The sharing of anonymized data from this study is restricted due to ethical and legal constrictions. Data contains sensitive personal health information, which is protected under The Personal Data Protection Act, thus making all data requests subject to Institutional Review Board (IRB) approval. Per Chang Gung Memorial Hospital (CGMH) IRB, the data that support the findings of this study are restricted for transmission to those outside the primary investigative team. Data sharing with investigators outside the team requires IRB approval. All requests for anonymized data will be reviewed by the research team and then submitted to the CGMH IRB for approval. Any requests for data should be directed to Dr Siew Tzuh Tang at email@example.com.
Specifications for MPlus codes for statistical analyses are available from the first and corresponding authors upon reasonable request.
Acute Physiology and Chronic Health Evaluation
Comparative fit index
Cross-lagged panel modeling
Hospital Anxiety and Depression Scale
HADS anxiety subscale
HADS depression subscale
Intensive care unit
Impact of Event Scale-Revised
Post-traumatic stress disorder
Root mean square error of approximation
Standardized root mean square residual
Bekelman JE, Halpern SD, Blankart CR, et al. Comparison of site of death, health care utilization, and hospital expenditures for patients dying with cancer in 7 developed countries. JAMA. 2016;315:272–83.
Chaudhuri D, Tanuseputro P, Herritt B, D’Egidio G, Chalifoux M, Kyeremanteng K. Critical care at the end of life: a population-level cohort study of cost and outcomes. Crit Care. 2017;21:124.
Teno JM, Gozalo P, Trivedi AN, et al. Site of death, place of care, and health care transitions among US Medicare beneficiaries, 2000–2015. JAMA. 2018;320:264–71.
Armstrong RA, Kane AD, Kursumovic E, Oglesby FC, Cook TM. Mortality in patients admitted to intensive care with COVID-19: an updated systematic review and meta-analysis of observational studies. Anaesthesia. 2021;76:537–48.
Johnson CC, Suchyta MR, Darowski ES, et al. Psychological sequelae in family caregivers of critically ill intensive care unit patients. A systematic review. Ann Am Thorac Soc. 2019;16:894–909.
Davidson JE, Jones C, Bienvenu OJ. Family response to critical illness: postintensive care syndrome-family. Crit Care Med. 2012;40:618–24.
Azoulay E, Pochard F, Kentish-Barnes N, et al. Risk of posttraumatic stress symptoms in family members of intensive care unit patients. Am J Respir Crit Care Med. 2005;171:987–94.
Siegel MD, Hayes E, Vanderwerker LC, Loseth DB, Prigerson HG. Psychiatric illness in the next of kin of patients who die in the intensive care unit. Crit Care Med. 2008;36:1722–8.
Anderson WG, Arnold RM, Angus DC, Bryce CL. Posttraumatic stress and complicated grief in family members of patients in the intensive care unit. J Gen Intern Med. 2008;23:1871–6.
Kentish-Barnes N, Chaize M, Seegers V, et al. Complicated grief after death of a relative in the intensive care unit. Eur Respir J. 2015;45:1341–52.
Hartog CS, Schwarzkopf D, Riedemann NC, et al. End-of-life care in the intensive care unit: a patient-based questionnaire of intensive care unit staff perception and relatives’ psychological response. Palliat Med. 2015;29:336–45.
Jensen HI, Gerritsen RT, Koopmans M, et al. Families’ experiences of intensive care unit quality of care: development and validation of a european questionnaire (euroQ2). J Crit Care. 2015;30:884–90.
Kentish-Barnes N, Seegers V, Legriel S, et al. CAESAR: a new tool to assess relatives’ experience of dying and death in the ICU. Intensive Care Med. 2016;42:995–1002.
Robert R, Le Gouge A, Kentish-Barnes N, et al. Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study). Intensive Care Med. 2017;43:1793–807.
Wendlandt B, Ceppe A, Choudhury S, et al. Risk factors for post-traumatic stress disorder symptoms in surrogate decision-makers of patients with chronic critical illness. Ann Am Thorac Soc. 2018;15:1451–8.
Petrinec AB, Martin BR. Post-intensive care syndrome symptoms and health-related quality of life in family decision-makers of critically ill patients. Palliat Support Care. 2018;16:719–24.
Gries CJ, Engelberg RA, Kross EK, et al. Predictors of symptoms of posttraumatic stress and depression in family members after patient death in the ICU. Chest. 2010;137:280–7.
Kross EK, Engelberg RA, Gries CJ, et al. ICU care associated with symptoms of depression and posttraumatic stress disorder among family members of patients who die in the ICU. Chest. 2011;139:795–801.
Probst DR, Gustin JL, Goodman LF, et al. ICU versus non-ICU hospital death: family member complicated grief, posttraumatic stress, and depressive symptoms. J Palliat Med. 2016;19:387–93.
Downar J, Koo E, des Ordons AR, et al. Prevalence and predictors of severe grief reactions and desire for support following a death in the intensive care unit: a multicentre observational study. Intensive Care Med. 2018;44:521–2.
Trevick SA, Lord AS. Post-traumatic stress disorder and complicated grief are common in caregivers of neuro-ICU patients. Neurocrit Care. 2017;26:436–43.
Layne CM, Kaplow JB, Oosterhoff B, Hill R, Pynoos RS. The interplay between posttraumatic stress and grief reactions in traumatically bereaved adolescents: when trauma, bereavement, and adolescence converge. Adolesc Psychiatry. 2017;7:220–39.
Ter Meulen WG, Draisma S, van Hemert AM, et al. Depressive and anxiety disorders in concert-A synthesis of findings on comorbidity in the NESDA study. J Affect Disord. 2021;284:85–97.
Kang B, Xu H, McConnell ES. Neurocognitive and psychiatric comorbidities of posttraumatic stress disorder among older veterans: a systematic review. Int J Geriatr Psychiatry. 2019;34:522–38.
Ginzburg K, Ein-Dor T, Solomon Z. Comorbidity of posttraumatic stress disorder, anxiety and depression: a 20-year longitudinal study of war veterans. J Affect Disord. 2010;123:249–57.
Nichter B, Norman S, Haller M, Pietrzak RH. Physical health burden of PTSD, depression, and their comorbidity in the U.S. veteran population: morbidity, functioning, and disability. J Psychosom Res. 2019;124:109744.
Nichter B, Norman S, Haller M, Pietrzak RH. Psychological burden of PTSD, depression, and their comorbidity in the U.S. veteran population: suicidality, functioning, and service utilization. J Affect Disord. 2019;256:633–40.
Roberts AL, Kubzansky LD, Chibnik LB, Rimm EB, Koenen KC. Association of posttraumatic stress and depressive symptoms with mortality in women. JAMA Netw Open. 2020;3:e2027935.
Kline AC, Cooper AA, Rytwinski NK, Feeny NC. The effect of concurrent depression on PTSD outcomes in trauma-focused psychotherapy: a meta-analysis of randomized controlled trials. Behav Ther. 2021;52:250–66.
Stander VA, Thomsen CJ, Highfill-McRoy RM. Etiology of depression comorbidity in combat-related PTSD: a review of the literature. Clin Psychol Rev. 2014;34:87–98.
Littlefield AK, King KM, Acuff SF, Foster KT, Murphy JG, Witkiewitz K. Limitations of cross-lagged panel models in addiction research and alternative models: an empirical example using project MATCH. Psychol Addict Behav. 2021 Jun;3. https://doi.org/10.1037/adb0000750. Epub ahead of print.
Tang ST, Huang CC, Hu TH, Lo ML, Chou WC, Chuang LP, Chiang MC. End-of-life-care quality in intensive care units is associated with family surrogates’ severe anxiety- and depressive symptoms during their first 6 months of bereavement. Crit Care Med. 2021;49:27–37.
Tang ST, Huang CC, Hu TH, Chou WC, Chuang LP, Chiang MC. Course and predictors of posttraumatic stress-related symptoms among family members of deceased ICU patients during the first year of bereavement. Crit Care. 2021;25:282.
McAdam JL, Dracup KA, White DB, Fontaine DK, Puntillo KA. Symptom experiences of family members of intensive care unit patients at high risk for dying. Crit Care Med. 2010;38:1078–85.
Weiss DS, Marmar CR. The impact of event scale—revised. In: Wilson JP, Keane TM, editors. Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. pp. 399–411.
Zigmond AS, Snaith PR. The hospital anxiety and depression scale (HADS). Acta Psychiatr Scand. 1983;67:361–71.
Usami S, Todo N, Murayama K. Modeling reciprocal effects in medical research: critical discussion on the current practices and potential alternative models. PLoS ONE. 2019;14:e0209133.
Burant CJ. A methodological note: an introduction to autoregressive models. Int J Aging Hum Dev. 2021 Dec;6:914150211066554. https://doi.org/10.1177/00914150211066554. Epub ahead of print.
Biesanz JC. Autoregressive longitudinal models. In: Hoyle RH, editor. Handbook of structural equation modeling. New York: Guilford Press; 2012. pp. 459–71.
Asendorpf JB. (2021). Modeling developmental processes. In J. R. Rauthmann, editor, Handbook of personality dynamics and processes. pp. 815–835. London, UK.
Hu L, Bentler PM. Evaluating model fit. In: Hoyle RH, editor. Structural equation modeling: concepts, issues, and applications. Thousand Oaks, CA: Sage; 1995. pp. 76–99.
Browne MW, Cudeck R. Alternative ways of assessing model fit. In: Bollen K, Long J, editors. Testing structural equation models. Newbury Park, CA: Sage; 1993. pp. 136–62.
Kline RB. Principles and practices of structural equation modeling. New York, NY: Guilford Press; 2005.
Glad KA, Stensland S, Czajkowski NO, Boelen PA, Dyb G. The longitudinal association between symptoms of posttraumatic stress and complicated grief: a random intercepts cross-lag analysis. Psychol Trauma. 2022;14(3):386–92.
Kaplow JB, Layne CM, Saltzman WR, Cozza SJ, Pynoos RS. Using multidimensional grief theory to explore the effects of deployment, reintegration, and death on military youth and families. Clin Child Fam Psychol Rev. 2013;16:322–40.
Maciejewski PK, Zhang B, Block SD, Prigerson HG. An empirical examination of the stage theory of grief. JAMA. 2007;297:716–23.
Hammen C. Stress and depression. Annu Rev Clin Psychol. 2005;1:293–319.
Boelen PA, Eisma MC. Anxious and depressive avoidance behavior in post-loss psychopathology: a longitudinal study. Anxiety Stress Coping. 2015;28:587–600.
Flory JD, Yehuda R. Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations. Dialogues Clin Neurosci. 2015;17:141–50.
Chow AYM. Anticipatory anniversary effects and bereavement: development of an integrated explanatory model. J Loss Trauma. 2009;15:54–68.
Jacobson NC, Newman MG. Anxiety and depression as bidirectional risk factors for one another: a meta-analysis of longitudinal studies. Psychol Bull. 2017;143:1155–200.
Van Ameringen M. Comorbid anxiety and depression in adults: Epidemiology, clinical manifestations, and diagnosis. UpToDate. 2022. https://www.uptodate.com/contents/comorbid-anxiety-and-depression-in-adults-epidemiology-clinical-manifestations-and-diagnosis. Accessed on 2023/4/21.
The authors acknowledge Erica Light as language editor.
National Health Research Institutes (NHRI-EX111-10704PI) with partial support from Ministry of Science and Technology (MOST 110-2314-B-182-009-MY3) and Chang Gung Memorial Hospital (BMRP888). No funding sources had any role in designing and conducting the study; collecting, managing, analyzing, and interpreting the data; preparing, reviewing, or approving the article; and in the decision to submit the report for publication. The views expressed in this article do not communicate an official position of the funding sources.
The authors declare no financial or other conflict of interest.
Ethics approval and consent to participate
This study was conducted with the approval for human subject research of the central Institutional Review Board of the study sites (Chang Gung Medical Foundation, Institutional Review Board; approval number: No: 201700343B0). All methods (study procedures and reporting of the study findings) were carried out in accordance with relevant guidelines and regulations (Declaration of Helsinki). Each family surrogate signed informed consent for participation.
Consent for publication
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
. Comparisons of patient characteristics across participation status during bereavement follow-ups (N = 289)a. Supplemental Table 2. Comparisons of family characteristics across participation status during bereavement follow-ups (N = 289)a. Supplemental Table 3. Comparisons of psychological distress of family characteristics across participation status during bereavement follow-ups (N=321)a
About this article
Cite this article
Wen, FH., Juang, YY., Prigerson, H.G. et al. Temporal reciprocal relationships among anxiety, depression, and posttraumatic stress disorder for family surrogates from intensive care units over their first two bereavement years. BMC Psychiatry 23, 412 (2023). https://doi.org/10.1186/s12888-023-04916-4
- Temporal relationships
- ICU care
- End-of-life care
- Family members | <urn:uuid:6528ff93-f2fe-4dc0-9592-5aaa69f4af4c> | CC-MAIN-2023-40 | https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-04916-4 | 2023-09-28T18:38:50Z | s3://commoncrawl/crawl-data/CC-MAIN-2023-40/segments/1695233510427.16/warc/CC-MAIN-20230928162907-20230928192907-00199.warc.gz | en | 0.881182 | 7,769 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.