Interpreting PPV and NPV of Diagnostic Tests with Uncertain Prevalence.

Objective: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease.

Gamified Closed-Loop Intervention Enhances Tic Suppression in Children: A Randomized Trial.

Background: Gamification of behavioral intervention for tic disorders (TDs) potentially enhances compliance and offers key clinical advantages. By delivering immediate positive feedback upon tic-suppression, games may counteract negative reinforcement, which presumably contribute to tic consolidation by relieving uncomfortable premonitory urges.

Objectives: We developed a gamified protocol (XTics), which leverages this potential by combining gamified tic-triggering with immediate feedback, and evaluated its clinical value in enhancing tic suppression.

Evidence and uncertainty: An info-gap analysis of uncertainty-augmenting evidence.

Decisions in many disciplines are based on understanding and evidence. More evidence is better than less when it enhances the decision-maker's understanding. This is achieved by reducing uncertainty confronting the decision-maker and reducing the potential for misunderstanding and failure.

The role for ambulatory electrocardiogram monitoring in the diagnosis and prognostication of Brugada syndrome: a sub-study of the Rare Arrhythmia Syndrome Evaluation (RASE) Brugada study.

Aims: Brugada syndrome (BrS) diagnosis and risk stratification rely on the presence of a spontaneous type 1 (spT1) electrocardiogram (ECG) pattern; however, its spontaneous fluctuations may lead to misdiagnosis and risk underestimation. This study aims to assess the role for repeat high precordial lead (HPL) resting and ambulatory ECG monitoring in identifying a spT1, and evaluate its prognostic role.

Methods And Results: HPL resting and ambulatory monitoring ECGs of BrS subjects were reviewed retrospectively, and the presence of a spT1 associated with ventricular dysrhythmias and sudden cardiac death (SCD).

Impact of movie and video game elements on tic manifestation in children.

Background And Purpose: Children in developed countries spend a significant portion of their waking hours engaging with audiovisual content and video games. The impact of media consumption on children's health and well-being has been widely studied, including its effects on tic disorders. Previous studies have shown that tic frequency can both increase and decrease during activities like gaming and television watching, resulting in mixed findings.

Continuous symmetry and chirality measures: approximate algorithms for large molecular structures.

Quantifying imperfect symmetry of molecules can help explore the sources, roles and extent of structural distortion. Based on the established methodology of continuous symmetry and chirality measures, we develop a set of three-dimensional molecular descriptors to estimate distortion of large structures. These three-dimensional geometrical descriptors quantify the gap between the desirable symmetry (or chirality) and the actual one.

Managing uncertainty in decision-making for conservation science.

Science-based decision-making is the ideal. However, scientific knowledge is incomplete, and sometimes wrong. Responsible science-based policy, planning, and action must exploit knowledge while managing uncertainty.

Forced Diuresis with Matched Isotonic Intravenous Hydration Prevents Renal Contrast Media Accumulation.

The accumulation of contrast media in the kidneys might lead to contrast-induced acute kidney injury. In this prospective, controlled observational study, we aimed to evaluate whether forced diuresis with matched isotonic intravenous hydration prevents the accumulation of contrast media in the kidneys of patients undergoing cardiac interventional procedures. We compared the intensity of contrast media accumulation as observed in nephrograms following these procedures, with and without peri-procedural controlled renal flushing.

Genetics of sudden cardiac death.

Purpose Of Review: Numerous cardiac diseases may cause sudden cardiac death (SCD), and a genetic basis for SCD has been established in the inherited cardiac conditions (ICCs). Previously, ICCs were thought to have a Mendelian inheritance pattern, wherein a rare pathogenic/likely pathogenic variant in a known diseasecausing gene conferred risk. This inheritance model, however, could not explain a large proportion of cases.

Generation and characterization of iPSC lines from two nuclear envelopathy patients with a homozygous nonsense mutation in the TOR1AIP1 gene.

LAP1 is an inner nuclear membrane protein encoded by TOR1AIP1. A homozygous c.961C > T loss of function mutation in TOR1AIP1 that affects both isoforms of LAP1 was recently described.

Robust Policy in Times of Pandemic.

The pandemic exposes policymakers to fundamental uncertainties about future economic scenarios. While policymakers have to act forcefully to mitigate the impact on the economy, these conditions call for policy strategies that are also robust to uncertainty. This article compares two concepts of robust strategies: robust control and robust satisficing.

Sex-Related Differences in Cardiac Channelopathies: Implications for Clinical Practice.

Sex-related differences in prevalence, clinical presentation, and outcome of cardiac channelopathies are increasingly recognized, despite their autosomal transmission and hence equal genetic predisposition among sexes. In congenital long-QT syndrome, adult women carry a greater risk for Torsades de pointes and sudden cardiac death than do men. In contrast, Brugada syndrome is observed predominantly in adult men, with a considerably higher risk of arrhythmic sudden cardiac death in adult men than in women.

Brugada syndrome and reduced right ventricular outflow tract conduction reserve: a final common pathway?

Brugada syndrome (BrS) was first described as a primary electrical disorder predisposing to the risk of sudden cardiac death and characterized by right precordial lead ST elevation. Early description of right ventricular structural abnormalities and of right ventricular outflow tract (RVOT) conduction delay in BrS patients set the stage for the current controversy over the pathophysiology underlying the syndrome: channelopathy or cardiomyopathy; repolarization or depolarization. This review examines the current understanding of the BrS substrate, its genetic and non-genetic basis, theories of pathophysiology, and the clinical implications thereof.

Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening.

Over the years, numerous groups have employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a superb human-compatible model for investigating the function and dysfunction of cardiomyocytes, drug screening and toxicity, disease modeling and for the development of novel drugs for heart diseases. In this review, we discuss the broad use of iPSC-CMs for drug development and disease modeling, in two related themes. In the first theme-drug development, adverse drug reactions, mechanisms of cardiotoxicity and the need for efficient drug screening protocols-we discuss the critical need to screen old and new drugs, the process of drug development, marketing and Adverse Drug reactions (ADRs), drug-induced cardiotoxicity, safety screening during drug development, drug development and patient-specific effect and different mechanisms of ADRs.

JingleBells: A Repository of Immune-Related Single-Cell RNA-Sequencing Datasets.

Recent advances in single-cell RNA-sequencing (scRNA-seq) technology increase the understanding of immune differentiation and activation processes, as well as the heterogeneity of immune cell types. Although the number of available immune-related scRNA-seq datasets increases rapidly, their large size and various formats render them hard for the wider immunology community to use, and read-level data are practically inaccessible to the non-computational immunologist. To facilitate datasets reuse, we created the JingleBells repository for immune-related scRNA-seq datasets ready for analysis and visualization of reads at the single-cell level (http://jinglebells.

Reasoned Decision Making Without Math? Adaptability and Robustness in Response to Surprise.

Many real-world planning and decision problems are far too uncertain, too variable, and too complicated to support realistic mathematical models. Nonetheless, we explain the usefulness, in these situations, of qualitative insights from mathematical decision theory. We demonstrate the integration of info-gap robustness in decision problems in which surprise and ignorance are predominant and where personal and collective psychological factors are critical.

A tunable silk-alginate hydrogel scaffold for stem cell culture and transplantation.

One of the major challenges in regenerative medicine is the ability to recreate the stem cell niche, which is defined by its signaling molecules, the creation of cytokine gradients, and the modulation of matrix stiffness. A wide range of scaffolds has been developed in order to recapitulate the stem cell niche, among them hydrogels. This paper reports the development of a new silk-alginate based hydrogel with a focus on stem cell culture.

A new multicriteria risk mapping approach based on a multiattribute frontier concept.

Invasive species risk maps provide broad guidance on where to allocate resources for pest monitoring and regulation, but they often present individual risk components (such as climatic suitability, host abundance, or introduction potential) as independent entities. These independent risk components are integrated using various multicriteria analysis techniques that typically require prior knowledge of the risk components' importance. Such information is often nonexistent for many invasive pests.