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We discuss probabilistic neural networks with a fixed internal representation as models for machine understanding. Here understanding is intended as mapping data to an already existing representation which encodes an {\em a priori} organisation of the feature space. We derive the internal representation by requiring that it satisfies the principles of maximal relevance and of maximal ignorance about how different features are combined. We show that, when hidden units are binary variables, these two principles identify a unique model -- the Hierarchical Feature Model (HFM) -- which is fully solvable and provides a natural interpretation in terms of features. We argue that learning machines with this architecture enjoy a number of interesting properties, like the continuity of the representation with respect to changes in parameters and data, the possibility to control the level of compression and the ability to support functions that go beyond generalisation. We explore the behaviour of the model with extensive numerical experiments and argue that models where the internal representation is fixed reproduce a learning modality which is qualitatively different from that of traditional models such as Restricted Boltzmann Machines.

Alzheimer's disease has an increasing prevalence in the population world-wide, yet current diagnostic methods based on recommended biomarkers are only available in specialized clinics. Due to these circumstances, Alzheimer's disease is usually diagnosed late, which contrasts with the currently available treatment options that are only effective for patients at an early stage. Blood-based biomarkers could fill in the gap of easily accessible and low-cost methods for early diagnosis of the disease. In particular, immune-based blood-biomarkers might be a promising option, given the recently discovered cross-talk of immune cells of the central nervous system with those in the peripheral immune system. With the help of machine learning algorithms and mechanistic modeling approaches, such as agent-based modeling, an in-depth analysis of the simulation of cell dynamics is possible as well as of high-dimensional omics resources indicative of pathway signaling changes. Here, we give a background on advances in research on brain-immune system cross-talk in Alzheimer's disease and review recent machine learning and mechanistic modeling approaches which leverage modern omics technologies for blood-based immune system-related biomarker discovery.

We study the severity of conflict-related violence in Colombia at an unprecedented granular scale in space and across time. Splitting the data into different geographical regions and different historically-relevant eras, we uncover variations in the patterns of conflict severity which we then explain in terms of local conflict actors' different collective behaviors and/or conditions using a simple mathematical model of conflict actors' grouping dynamics (coalescence and fragmentation). Specifically, variations in the approximate scaling values of the distributions of event lethalities can be explained by the changing strength ratio of the local conflict actors for distinct conflict periods and organizational regions. In this way, our findings open the door to a new granular spectroscopy of human conflicts in terms of local conflict actor strength ratios for any armed conflict.

It is becoming increasingly emphasis on the importance of LLM participating in clinical diagnosis decision-making. However, the low specialization refers to that current medical LLMs can not provide specific medical advice, which are more like a medical Q\&A. And there is no suitable clinical guidance tree data set that can be used directly with LLM. To address this issue, we first propose LLM-executavle clinical guidance tree(CGT), which can be directly used by large language models, and construct medical diagnostic decision-making dataset (MedDM), from flowcharts in clinical practice guidelines. We propose an approach to screen flowcharts from medical literature, followed by their identification and conversion into standardized diagnostic decision trees. Constructed a knowledge base with 1202 decision trees, which came from 5000 medical literature and covered 12 hospital departments, including internal medicine, surgery, psychiatry, and over 500 diseases.Moreover, we propose a method for reasoning on LLM-executable CGT and a Patient-LLM multi-turn dialogue framework.

Dynamic treatment regimes (DTRs) formalize medical decision-making as a sequence of rules for different stages, mapping patient-level information to recommended treatments. In practice, estimating an optimal DTR using observational data from electronic medical record (EMR) databases can be complicated by covariates that are missing not at random (MNAR) due to informative monitoring of patients. Since complete case analysis can result in consistent estimation of outcome model parameters under the assumption of outcome-independent missingness \citep{Yang_Wang_Ding_2019}, Q-learning is a natural approach to accommodating MNAR covariates. However, the backward induction algorithm used in Q-learning can introduce complications, as MNAR covariates at later stages can result in MNAR pseudo-outcomes at earlier stages, leading to suboptimal DTRs, even if outcome variables are fully observed. To address this unique missing data problem in DTR settings, we propose two weighted Q-learning approaches where inverse probability weights for missingness of the pseudo-outcomes are obtained through estimating equations with valid nonresponse instrumental variables or sensitivity analysis. Asymptotic properties of the weighted Q-learning estimators are derived and the finite-sample performance of the proposed methods is evaluated and compared with alternative methods through extensive simulation studies. Using EMR data from the Medical Information Mart for Intensive Care database, we apply the proposed methods to investigate the optimal fluid strategy for sepsis patients in intensive care units.

The United States opioid crisis contributed to 80,411 fatalities in 2021. It has strained hospitals, treatment facilities, and law enforcement agencies due to the enormous resources and procedures needed to respond to the crisis. As a result, many individuals who use opioids never receive or finish the treatment they need and instead have many interactions with hospitals or the criminal justice system. This paper introduces a discrete event simulation model that evaluates three opioid use disorder treatment policies: arrest diversion, re-entry case management, and overdose diversion. Publicly available data from 2011 to 2019 in Dane County, Wisconsin, was used to forecast opioid-related outcomes through 2032. Through analyzing a variety of policy-mix implementations, the study offers a versatile framework for evaluating policies at various implementation levels. The results demonstrate that treatment policies that create new pathways and programming by utilizing treatment services and successfully divert at least 20% of eligible individuals can lead to more opioid-resilient communities. The benefits increase when more policies are enacted and/or are offered to more individuals. We assume communities invest in increasing treatment capacity to meet increased treatment demand. In policy-mixes where societal savings from decreased opioid use, hospital encounters, and opioid-related arrests outweigh the costs of opioid use disorder treatment, the 2032 total savings range from $7.04 to $29.73 million. To reverse the opioid crisis within a community, treatment policies may need to be combined with other strategies, such as harm reduction, supply reduction, and use prevention.

We consider a setting where a population of artificial learners is given, and the objective is to optimize aggregate measures of performance, under constraints on training resources. The problem is motivated by the study of peer learning in human educational systems. In this context, we study natural knowledge diffusion processes in networks of interacting artificial learners. By `natural', we mean processes that reflect human peer learning where the students' internal state and learning process is mostly opaque, and the main degree of freedom lies in the formation of peer learning groups by a coordinator who can potentially evaluate the learners before assigning them to peer groups. Among else, we empirically show that such processes indeed make effective use of the training resources, and enable the design of modular neural models that have the capacity to generalize without being prone to overfitting noisy labels.

Diabetic retinopathy (DR) is a growing health problem worldwide and is a leading cause of visual impairment and blindness, especially among working people aged 20-65. Its incidence is increasing along with the number of diabetes cases, and it is more common in developed countries than in developing countries. Recent research in the field of diabetic retinopathy diagnosis is using advanced technologies, such as analysis of images obtained by ophthalmoscopy. Automatic methods for analyzing eye images based on neural networks, deep learning and image analysis algorithms can improve the efficiency of diagnosis. This paper describes an automatic DR diagnosis method that includes processing and analysis of ophthalmoscopic images of the eye. It uses morphological algorithms to identify the optic disc and lesions characteristic of DR, such as microaneurysms, hemorrhages and exudates. Automated DR diagnosis has the potential to improve the efficiency of early detection of this disease and contribute to reducing the number of cases of diabetes-related visual impairment. The final step was to create an application with a graphical user interface that allowed retinal images taken at cooperating ophthalmology offices to be uploaded to the server. These images were then analyzed using a developed algorithm to make a diagnosis.

Spatio-temporal pathogen spread is often partially observed at the metapopulation scale. Available data correspond to proxies and are incomplete, censored and heterogeneous. Moreover, representing such biological systems often leads to complex stochastic models. Such complexity together with data characteristics make the analysis of these systems a challenge. Our objective was to develop a new inference procedure to estimate key parameters of stochastic metapopulation models of animal disease spread from longitudinal and spatial datasets, while accurately accounting for characteristics of census data. We applied our procedure to provide new knowledge on the regional spread of \emph{Mycobacterium avium} subsp. \emph{paratuberculosis} (\emph{Map}), which causes bovine paratuberculosis, a worldwide endemic disease. \emph{Map} spread between herds through trade movements was modeled with a stochastic mechanistic model. Comprehensive data from 2005 to 2013 on cattle movements in 12,857 dairy herds in Brittany (western France) and partial data on animal infection status in 2,278 herds sampled from 2007 to 2013 were used. Inference was performed using a new criterion based on a Monte-Carlo approximation of a composite likelihood, coupled to a numerical optimization algorithm (Nelder-Mead Simplex-like). Our criterion showed a clear superiority to alternative ones in identifying the right parameter values, as assessed by an empirical identifiability on simulated data. Point estimates and profile likelihoods allowed us to establish the initial state of the system, identify the risk of pathogen introduction from outside the metapopulation, and confirm the assumption of the low sensitivity of the diagnostic test. Our inference procedure could easily be applied to other spatio-temporal infection dynamics, especially when ABC-like methods face challenges in defining relevant summary statistics.

Breast cancer remains a global challenge, causing over 1 million deaths globally in 2018. To achieve earlier breast cancer detection, screening x-ray mammography is recommended by health organizations worldwide and has been estimated to decrease breast cancer mortality by 20-40%. Nevertheless, significant false positive and false negative rates, as well as high interpretation costs, leave opportunities for improving quality and access. To address these limitations, there has been much recent interest in applying deep learning to mammography; however, obtaining large amounts of annotated data poses a challenge for training deep learning models for this purpose, as does ensuring generalization beyond the populations represented in the training dataset. Here, we present an annotation-efficient deep learning approach that 1) achieves state-of-the-art performance in mammogram classification, 2) successfully extends to digital breast tomosynthesis (DBT; "3D mammography"), 3) detects cancers in clinically-negative prior mammograms of cancer patients, 4) generalizes well to a population with low screening rates, and 5) outperforms five-out-of-five full-time breast imaging specialists by improving absolute sensitivity by an average of 14%. Our results demonstrate promise towards software that can improve the accuracy of and access to screening mammography worldwide.