Macrostate Data Clustering

We develop an effective nonhierarchical data clustering method using an analogy to the dynamic coarse graining of a stochastic system. Analyzing the eigensystem of an interitem transition matrix identifies fuzzy clusters corresponding to the metastable macroscopic states (macrostates) of a diffusive system. A "minimum uncertainty criterion" determines the linear transformation from eigenvectors to cluster-defining window functions. Eigenspectrum gap and cluster certainty conditions identify the proper number of clusters. The physically motivated fuzzy representation and associated uncertainty analysis distinguishes macrostate clustering from spectral partitioning methods. Macrostate data clustering solves a variety of test cases that challenge other methods.Comment: keywords: cluster analysis, clustering, pattern recognition, spectral graph theory, dynamic eigenvectors, machine learning, macrostates, classificatio

A web-based tool for eliciting probability distributions from experts

We present a web-based probability distribution elicitation tool: The MATCH Uncertainty Elicitation Tool. The Tool is designed to help elicit probability distributions about uncertain model parameters from experts, in situations where suitable data is either unavailable or sparse. The Tool is free to use, and offers five different techniques for eliciting univariate probability distributions. A key feature of the Tool is that users can log in from different sites and view and interact with the same graphical displays, so that expert elicitation sessions can be conducted remotely (in conjunction with tele- or videoconferencing). This will make probability elicitation easier in situations where it is difficult to interview experts in person. Even when conducting elicitation remotely, interviewers will be able to follow good elicitation practice, advise the experts, and provide instantaneous feedback and assistance

Researching the use of force: The background to the international project

This article provides the background to an international project on use of force by the police that was carried out in eight countries. Force is often considered to be the defining characteristic of policing and much research has been conducted on the determinants, prevalence and control of the use of force, particularly in the United States. However, little work has looked at police officers’ own views on the use of force, in particular the way in which they justify it. Using a hypothetical encounter developed for this project, researchers in each country conducted focus groups with police officers in which they were encouraged to talk about the use of force. The results show interesting similarities and differences across countries and demonstrate the value of using this kind of research focus and methodology

ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIVmac251SIV_{mac}251 Challenge

Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVΔnef, increased progressively over time, and was proportional to SIVΔnef replication. Persistent infection with SIVΔnef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against $SIV_{mac}251$ challenge, measures of ADCC activity were higher among the SIVΔnef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVΔnef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVΔnef

Physical activity and clustered cardiovascular disease risk factors in young children: a cross-sectional study (the IDEFICS study)

<p>Background The relevance of physical activity (PA) for combating cardiovascular disease (CVD) risk in children has been highlighted, but to date there has been no large-scale study analyzing that association in children aged ≤9 years of age. This study sought to evaluate the associations between objectively-measured PA and clustered CVD risk factors in a large sample of European children, and to provide evidence for gender-specific recommendations of PA.</p> <p>Methods Cross-sectional data from a longitudinal study in 16,224 children aged 2 to 9 were collected. Of these, 3,120 (1,016 between 2 to 6 years, 2,104 between 6 to 9 years) had sufficient data for inclusion in the current analyses. Two different age-specific and gender-specific clustered CVD risk scores associated with PA were determined. First, a CVD risk factor (CRF) continuous score was computed using the following variables: systolic blood pressure (SBP), total triglycerides (TG), total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c) ratio, homeostasis model assessment of insulin resistance (HOMA-IR), and sum of two skinfolds (score CRFs). Secondly, another CVD risk score was obtained for older children containing the score CRFs + the cardiorespiratory fitness variable (termed score CRFs + fit). Data used in the current analysis were derived from the IDEFICS (‘Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS’) study.</p> <p>Results In boys <6 years, the odds ratios (OR) for CVD risk were elevated in the least active quintile of PA (OR: 2.58) compared with the most active quintile as well as the second quintile for vigorous PA (OR: 2.91). Compared with the most active quintile, older children in the first, second and third quintiles had OR for CVD risk score CRFs + fit ranging from OR 2.69 to 5.40 in boys, and from OR 2.85 to 7.05 in girls.</p> <p>Conclusions PA is important to protect against clustering of CVD risk factors in young children, being more consistent in those older than 6 years. Healthcare professionals should recommend around 60 and 85 min/day of moderate-to-vigorous PA, including 20 min/day of vigorous PA.</p&gt

A Checklist for Medication Compliance and Persistence Studies Using Retrospective Databases

The increasing number of retrospective database studies related to medication compliance and persistence (C&P), and the inherent variability within each, has created a need for improvement in the quality and consistency of medication C&P research. This article stems from the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) efforts to develop a checklist of items that should be either included, or at least considered, when a retrospective database analysis of medication compliance or persistence is undertaken. This consensus document outlines a systematic approach to designing or reviewing retrospective database studies of medication C&P. Included in this article are discussions on data sources, measures of C&P, results reporting, and even conflict of interests. If followed, this checklist should improve the consistency and quality of C&P analyses, which in turn will help providers and payers understand the impact of C&P on health outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75562/1/j.1524-4733.2006.00139.x.pd

Nasal Host Response-Based Screening for Undiagnosed Respiratory Viruses: A Pathogen Surveillance and Detection Study

BACKGROUND: Symptomatic patients who test negative for common viruses are an important possible source of unrecognised or emerging pathogens, but metagenomic sequencing of all samples is inefficient because of the low likelihood of finding a pathogen in any given sample. We aimed to determine whether nasopharyngeal CXCL10 screening could be used as a strategy to enrich for samples containing undiagnosed viruses. METHODS: In this pathogen surveillance and detection study, we measured CXCL10 concentrations from nasopharyngeal swabs from patients in the Yale New Haven health-care system, which had been tested at the Yale New Haven Hospital Clinical Virology Laboratory (New Haven, CT, USA). Patients who tested negative for a panel of respiratory viruses using multiplex PCR during Jan 23-29, 2017, or March 3-14, 2020, were included. We performed host and pathogen RNA sequencing (RNA-Seq) and analysis for viral reads on samples with CXCL10 higher than 1 ng/mL or CXCL10 testing and quantitative RT-PCR (RT-qPCR) for SARS-CoV-2. We used RNA-Seq and cytokine profiling to compare the host response to infection in samples that were virus positive (rhinovirus, seasonal coronavirus CoV-NL63, or SARS-CoV-2) and virus negative (controls). FINDINGS: During Jan 23-29, 2017, 359 samples were tested for ten viruses on the multiplex PCR respiratory virus panel (RVP). 251 (70%) were RVP negative. 60 (24%) of 251 samples had CXCL10 higher than 150 pg/mL and were identified for further analysis. 28 (47%) of 60 CXCL10-high samples were positive for seasonal coronaviruses. 223 (89%) of 251 samples were PCR negative for 15 viruses and, of these, CXCL10-based screening identified 32 (13%) samples for further analysis. Of these 32 samples, eight (25%) with CXCL10 concentrations higher than 1 ng/mL and sufficient RNA were selected for RNA-Seq. Microbial RNA analysis showed the presence of influenza C virus in one sample and revealed RNA reads from bacterial pathobionts in four (50%) of eight samples. Between March 3 and March 14, 2020, 375 (59%) of 641 samples tested negative for 15 viruses on the RVP. 32 (9%) of 375 samples had CXCL10 concentrations ranging from 100 pg/mL to 1000 pg/mL and four of those were positive for SARS-CoV-2. CXCL10 elevation was statistically significant, and a distinguishing feature was found in 28 (8%) of 375 SARS-CoV-2-negative samples versus all four SARS-CoV-2-positive samples (p=4·4 × 10 INTERPRETATION: These results confirm CXCL10 as a robust nasopharyngeal biomarker of viral respiratory infection and support host response-based screening followed by metagenomic sequencing of CXCL10-high samples as a practical approach to incorporate clinical samples into pathogen discovery and surveillance efforts. FUNDING: National Institutes of Health, the Hartwell Foundation, the Gruber Foundation, Fast Grants for COVID-19 research from the Mercatus Center, and the Huffman Family Donor Advised Fund

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)

Although considerable improvement has occurred in the process of care for patients with ST-elevation myocardial infarction (STEMI), room for improvement exists (1–3). The purpose of the present guideline is to focus on the numerous advances in the diagnosis and management of patients with STEMI since 1999. This is reflected in the changed name of the guideline: “ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.” The final recommendations for indications for a diagnostic procedure, a particular therapy, or an intervention in patients with STEMI summarize both clinical evidence and expert opinion (Table 1).To provide clinicians with a set of recommendations that can easily be translated into the practice of caring for patients with STEMI, this guideline is organized around the chronology of the interface between the patient and the clinician. The full guideline is available at http://www.acc.org/clinical/guidelines/stemi/index.htm

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)