Daily Papers

High-dimensional count data arise in applications such as single-cell RNA sequencing and neural spike trains, where mappings between distributions across successive batches or time points form critical components of data analysis. The recent success of diffusion- and flow-based deep generative models for images, video, and text motivates extending these ideas to count-valued settings, but many existing methods either treat each count as a categorical state or transform counts into a continuous space, neither of which is natural or efficient when the count range is large. We propose count-FM, a flow-matching framework for count data based on a continuous-time birth-death process with local unit jumps. Count-FM learns marginal transitions efficiently in count space through simulation-free training of conditional transition rates, allowing transport between arbitrary count-distributed source and target populations. In simulation, count-FM variants achieve strong sample quality while using substantially fewer parameters. We further apply count-FM to scRNA-seq and neural spike-train data for unconditional generation, transport, and conditional generation. Across these tasks, count-FM yields improved sample quality, greater modeling efficiency, and interpretable transport paths.

Human aging is marked by a steady rise in the risk of dying with age-a process demographers call senescence. Over the past century, life expectancy has risen dramatically, but is this because we are aging slower, or simply starting it later? Vaupel hypothesizes that the pace at which individuals age may be constant, with gains in longevity coming from the delayed onset of senescence rather than its slowing down. We test this idea using a new framework that decomposes the pace of senescence into three components: a biological baseline, a long-term trend, and the cumulative impact of period shocks. Applying this to cohort mortality data above age 80 from 12 countries, we find that once period shocks are accounted for, there is no statistical evidence of a long-term trend, consistent with Vaupel's hypothesis. Analyses using lower starting ages yield the same qualitative conclusion. Rather than indicating a change in the process that drives senescence, these variations are consistent with echoes of shared historical events. These results suggest that while longevity has shifted, the rhythm of human aging may be conserved.

High-dimensional count data are common in scientific applications, but most diffusion and flow models are designed for continuous or categorical data, and generation often requires many sequential model evaluations. We propose Count Flow Map, a generative model that learns finite-time transitions directly in count space for one- or few-step generation. Our model directly learns stochastic transitions over finite time intervals, using Poisson births and Binomial deaths to preserve nonnegative integer counts without a predefined maximum. These transition models are trained to match the underlying local birth--death dynamics and to maintain consistency across step sizes. We characterize the connection between local dynamics and finite-time transition consistency and derive a bound on the generation error. After validating Count Flow Map in several simulations, including a high-dimensional, high-count setting, we apply it to single-cell drug perturbation prediction and neural population forecasting, where it captures perturbation responses and supports forecasts of high-activity events with only one or a few model evaluations. Together, these experiments demonstrate that Count Flow Map enables high-quality generation directly in count space across inference budgets, from one-step to few-step generation, using a single trained model.

Scientific measurements such as single-cell RNA (scRNA) sequencing often take the form of nonnegative integer counts, whereas continuous-state diffusion models approximate this discrete structure using continuous coordinates. Building on stochastic chemical reaction networks (CRNs), a class of count-native Markov jump processes, we introduce CRNDiff, a structured framework that combines count-space diffusion with inference-time conditioning on rare subpopulations. An independent birth--death instantiation yields a closed-form transition kernel for forward noising. This kernel enables reverse sampling via forward-filtering backward-sampling (FFBS) and supports data-driven selection of the terminal noising time, eliminating the need for a validation sweep. This tractability also lets us introduce tilted Feynman--Kac (FK) steering, a method for sampling target subpopulations from a frozen generator without retraining. By tilting posterior marginals before FK particle correction, steering mitigates importance-weight concentration when the target population is rare. Using scRNA-seq data from the human heart cell atlas, we test the ability of CRNDiff to generate cell-type-specific distributions. Across the three evaluated target populations, CRNDiff achieves the highest conditional fidelity among the evaluated generative models, with larger mean purity margins for rarer target populations. Generated cells preserve marker-level differential-expression structure. Replacing real training cells for the target classes with generated cells yields downstream classification performance approaching that of the real-data reference.

In this paper, we suggest a novel method for detecting mortality deceleration. We focus on the gamma-Gompertz frailty model and suggest the subtraction of a penalty in the log-likelihood function as an alternative to traditional likelihood inference and hypothesis testing. Over existing methods, our method offers advantages, such as avoiding the use of a p-value, hypothesis testing, and asymptotic distributions. We evaluate the performance of our approach by comparing it with traditional likelihood inference on both simulated and real mortality data. Results have shown that our approach is more accurate in detecting mortality deceleration and provides more reliable estimates of the underlying parameters. The proposed method is a significant contribution to the literature as it offers a powerful tool for analyzing mortality patterns.

The Makeham term is a crucial element in mortality modeling, representing a constant additive hazard that addresses background mortality factors unrelated to aging. Widely used in mortality analysis, this term enables the capture of risks not linked to age-related decline. This paper aims to explore the relationship between Makeham mortality models and competing risk frameworks, investigating how Makeham models can be analyzed within the context of competing risks. It provides insights into the mathematical properties, interpretation, and applicability of Makeham models in modeling mortality risks associated with various causes of death. Additionally, it demonstrates that competing risk models can be represented as mixture models, enhancing understanding of mortality dynamics. The contribution lies in showing that Makeham mortality models, when represented as mixtures, offer a straightforward specification that can accommodate unobserved heterogeneity and distinguish between senescent and extrinsic mortality. By expressing Makeham models as a convex combination of probability distributions, the paper allows the estimation of premature mortality profiles, particularly at older ages, where most deaths are assumed to be senescent. It also facilitates the estimation of senescent mortality, which is crucial for studying the aging process.

This paper presents a novel approach for modeling mortality rates above age 70 by proposing a mixture-based model. This model is compared to four other widely used models: the Beard, Gompertz, Makeham, and Perks models. Our model can capture the complex behavior of mortality rates at all ages, providing a more accurate representation of the data. To evaluate the performance of our model, we applied it to two countries with different data quality: Japan and Brazil. Our results show that the proposed model outperforms the other models in both countries, particularly in Japan where it obtained an absolute mean percentage error of less than 7%, while the other models presented values greater than 30%. This highlights the ability of our model to adapt to different data quality and country-specific mortality patterns. In summary, this paper presents a mixture-based model that captures the behavior of mortality rates at all ages and outperforms other widely used models in both high- and low-quality data settings. This model can improve mortality prediction and inform public health policy.

Whether the risk of death keeps climbing at extreme ages or levels off has divided researchers for a century. We show this conflict reflects a moving target. Using cohort data from twelve low-mortality populations, we find that mortality deceleration and plateau onset shift steadily later across cohorts born from the mid-19th to the early-20th century. The data support a plateau across the full cohort range, though evidence weakens for the youngest, incompletely observed cohorts. In these younger cohorts, deceleration begins near age 100, and the fitted plateau begins beyond age 108. Because past studies focused on different cohorts and fixed age ranges, they sampled different phases of the exact same shift. The mortality plateau has no fixed age: it has been rescheduled.

Over the past decade, machine learning has revolutionized computers' ability to analyze text through flexible computational models. Due to their structural similarity to written language, transformer-based architectures have also shown promise as tools to make sense of a range of multi-variate sequences from protein-structures, music, electronic health records to weather-forecasts. We can also represent human lives in a way that shares this structural similarity to language. From one perspective, lives are simply sequences of events: People are born, visit the pediatrician, start school, move to a new location, get married, and so on. Here, we exploit this similarity to adapt innovations from natural language processing to examine the evolution and predictability of human lives based on detailed event sequences. We do this by drawing on arguably the most comprehensive registry data in existence, available for an entire nation of more than six million individuals across decades. Our data include information about life-events related to health, education, occupation, income, address, and working hours, recorded with day-to-day resolution. We create embeddings of life-events in a single vector space showing that this embedding space is robust and highly structured. Our models allow us to predict diverse outcomes ranging from early mortality to personality nuances, outperforming state-of-the-art models by a wide margin. Using methods for interpreting deep learning models, we probe the algorithm to understand the factors that enable our predictions. Our framework allows researchers to identify new potential mechanisms that impact life outcomes and associated possibilities for personalized interventions.

\noindent The modal age at death is an increasingly used measure for understanding longevity and mortality patterns. However, existing estimation methods focus on point estimates, overlooking the inherent variability and uncertainty in mortality data. This study addresses this gap by introducing a probabilistic framework for estimating the probability distribution of the modal age at death. Using a multinomial model for age-specific death counts and leveraging a Gaussian approximation, our methodology captures variability while aligning with the discrete nature of mortality data. Empirical examples are based on mortality data from six different countries. By quantifying uncertainty around the modal age at death and improving robustness to data fluctuations, this approach offers valuable insights for demographic research and policy planning.

Age-specific mortality improvements are non-uniform, neither across ages nor across time. We propose a two-step procedure to estimate the rates of mortality improvement (RMI) in age-specific death rates (ASDR) at ages 85 and above for ten European countries from 1950 to 2019. In the first step, we smooth the raw death counts and estimate ASDR using four different methods: one parametric (gamma-Gompertz-Makeham), two non-parametric (P-splines and PCLM), and a novel Bayesian procedure to handle fluctuations resulting from ages with zero death counts. We compare the goodness of fit of the four smoothing methods and calculate the year-to-year ASDR differences according to the best-fitting one. We fit a piecewise linear function to these differences in the second step. The slope in each linear segment captures the average RMI in the respective year range. For each age, we calculate the goodness of fit in the last linear segment to assess how informative the estimated RMI of current mortality change is. The estimated rates of mortality improvement or deterioration (RMI) can be used to make short-term social, health, and social planning, as well as more precise mortality forecasts.

A compartmental deterministic model that allows (1) immunity from two stages of infection and carriage, and (2) disease induced death, is used in studying the dynamics of meningitis epidemic process in a closed population. It allows for difference in the transmission rate of infection to a susceptible by a carrier and an infective. It is generalized to allow a proportion ({\phi}) of those susceptibles infected to progress directly to infectives in stage I. Both models are used in this study. The threshold conditions for the spread of carrier and infectives in stage I are derived for the two models. Sensitivity analysis is performed on the reproductive number derived from the next generation matrix. The case-carrier ratio profile for various parameters and threshold values are shown. So also are the graphs of the total number ever infected as influenced by {\epsilon} and {\phi}. The infection transmission rate (eta), the odds in favor of a carrier, over an infective, in transmitting an infection to a susceptible ({\epsilon}) and the carrier conversion rate ({\phi}) to an infective in stage I, are identified as key parameters that should be subject of attention for any control intervention strategy. The case-carrier ratio profiles provide evidence of a critical case-carrier ratio attained before the number of reported cases grows to an epidemic level. They also provide visual evidence of epidemiological context, in this case, epidemic incidence (in later part of dry season) and endemic incidence (during rainy season). Results from total proportion ever infected suggest that the model, in which {\phi}=0 obtained, can adequately represent, in essence, the generalized model for this study.

Neonatal death is still a concerning reality for underdeveloped and even some developed countries. Worldwide data indicate that 26.693 babies out of 1,000 births die, according to Macro Trades. To reduce this number, early prediction of endangered babies is crucial. Such prediction enables the opportunity to take ample care of the child and mother so that early child death can be avoided. In this context, machine learning was used to determine whether a newborn baby is at risk. To train the predictive model, historical data of 1.4 million newborns was used. Machine learning and deep learning techniques such as logical regression, K-nearest neighbor, random forest classifier, extreme gradient boosting (XGBoost), convolutional neural network, and long short-term memory (LSTM) were implemented using the dataset to identify the most accurate model for predicting neonatal mortality. Among the machine learning algorithms, XGBoost and random forest classifier achieved the best accuracy with 94%, while among the deep learning models, LSTM delivered the highest accuracy with 99%. Therefore, using LSTM appears to be the most suitable approach to predict whether precautionary measures for a child are necessary.

De-identification of electronic health records (EHR) is a vital step towards advancing health informatics research and maximising the use of available data. It is a two-step process where step one is the identification of protected health information (PHI), and step two is replacing such PHI with surrogates. Despite the recent advances in automatic de-identification of EHR, significant obstacles remain if the abundant health data available are to be used to the full potential. Accuracy in de-identification could be considered a necessary, but not sufficient condition for the use of EHR without individual patient consent. We present here a comprehensive review of the progress to date, both the impressive successes in achieving high accuracy and the significant risks and challenges that remain. To best of our knowledge, this is the first paper to present a complete picture of end-to-end automatic de-identification. We review 18 recently published automatic de-identification systems -designed to de-identify EHR in the form of free text- to show the advancements made in improving the overall accuracy of the system, and in identifying individual PHI. We argue that despite the improvements in accuracy there remain challenges in surrogate generation and replacements of identified PHIs, and the risks posed to patient protection and privacy.

The face is a rich source of information that can be utilized to infer a person's biological age, sex, phenotype, genetic defects, and health status. All of these factors are relevant for predicting an individual's remaining lifespan. In this study, we collected a dataset of over 24,000 images (from Wikidata/Wikipedia) of individuals who died of natural causes, along with the number of years between when the image was taken and when the person passed away. We made this dataset publicly available. We fine-tuned multiple Convolutional Neural Network (CNN) models on this data, at best achieving a mean absolute error of 8.3 years in the validation data using VGGFace. However, the model's performance diminishes when the person was younger at the time of the image. To demonstrate the potential applications of our remaining lifespan model, we present examples of using it to estimate the average loss of life (in years) due to the COVID-19 pandemic and to predict the increase in life expectancy that might result from a health intervention such as weight loss. Additionally, we discuss the ethical considerations associated with such models.