Role of human infection challenge studies (HICs) in drug development for respiratory syncytial virus (RSV): systematic review and meta-analysis.

Background: Human infection challenge studies (HICs) are powerful in establishing early proof-of-concept for experimental drugs and understanding disease pathogenesis. A comprehensive assessment of HICs will allow to understand the viral load (VL) dynamics and symptom score kinetics of respiratory syncytial virus (RSV) and facilitate drug development for RSV.

Methods: In this study, we conducted a systematic search of double-blind, placebo-controlled RSV HICs using Biosis Previews, Embase, Ovid MEDLINE, PubMed, ClinicalTrials.

Transition to synchronization in the adaptive Sakaguchi-Kuramoto model with higher-order interactions.

We investigate the phenomenon of transition to synchronization in the Sakaguchi-Kuramoto model in the presence of higher-order interactions and global order parameter adaptation. The investigation is done by performing extensive numerical simulations and low-dimensional modeling of the system. Numerical simulations of the full system show both continuous (second-order) as well as discontinuous transitions.

Impact of phase lag on synchronization in frustrated Kuramoto model with higher-order interactions.

The study of first order transition (explosive synchronization) in an ensemble (network) of coupled oscillators has been the topic of paramount interest among the researchers for more than one decade. Several frameworks have been proposed to induce explosive synchronization in a network and it has been reported that phase frustration in a network usually suppresses first order transition in the presence of pairwise interactions among the oscillators. However, on the contrary, by considering networks of phase frustrated coupled oscillators in the presence of higher-order interactions (up to 2-simplexes) we show here, under certain conditions, phase frustration can promote explosive synchronization in a network.

Perfect synchronization in complex networks with higher-order interactions.

Achieving perfect synchronization in a complex network, specially in the presence of higher-order interactions (HOIs) at a targeted point in the parameter space, is an interesting, yet challenging task. Here we present a theoretical framework to achieve the same under the paradigm of the Sakaguchi-Kuramoto (SK) model. We analytically derive a frequency set to achieve perfect synchrony at some desired point in a complex network of SK oscillators with higher-order interactions.

Dimension reduction in higher-order contagious phenomena.

We investigate epidemic spreading in a deterministic susceptible-infected-susceptible model on uncorrelated heterogeneous networks with higher-order interactions. We provide a recipe for the construction of one-dimensional reduced model (resilience function) of the N-dimensional susceptible-infected-susceptible dynamics in the presence of higher-order interactions. Utilizing this reduction process, we are able to capture the microscopic and macroscopic behavior of infectious networks.

Estimating Burden of Mortality due to Excess Body Mass Index in the US Adult Population by Combining Evidence from a Mendelian Randomization Study and National Health Surveys.

Importance: Assessment of the burden of mortality due to excess body weight in a population and its subgroups is important for designing health policies for interventions. Mendelian randomization (MR) studies can provide an opportunity to correct for unmeasured confounding bias present in observational studies, but such evidence has not been used to assess population burden of mortality due to excess BMI.

Objective: Combine results from a recent Mendelian randomization (MR) study and data from the National Health Surveys to estimate preventable fraction (PF) of 10-year all-cause and cause-specific mortality by different degrees of BMI reduction in the US adult population and underlying risk strata.

Early warnings for multi-stage transitions in dynamics on networks.

Successfully anticipating sudden major changes in complex systems is a practical concern. Such complex systems often form a heterogeneous network, which may show multi-stage transitions in which some nodes experience a regime shift earlier than others as an environment gradually changes. Here we investigate early warning signals for networked systems undergoing a multi-stage transition.

Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common control subjects.

Genome-wide association studies (GWASs) have been performed to identify host genetic factors for a range of phenotypes, including for infectious diseases. The use of population-based common control subjects from biobanks and extensive consortia is a valuable resource to increase sample sizes in the identification of associated loci with minimal additional expense. Non-differential misclassification of the outcome has been reported when the control subjects are not well characterized, which often attenuates the true effect size.

Accuracy of a one-dimensional reduction of dynamical systems on networks.

Resilience is an ability of a system with which the system can adjust its activity to maintain its functionality when it is perturbed. To study resilience of dynamics on networks, Gao et al. [Nature (London) 530, 307 (2016)0028-083610.

Logistic regression analysis of two-phase studies using generalized method of moments.

Two-phase designs can reduce the cost of epidemiological studies by limiting the ascertainment of expensive covariates or/and exposures to an efficiently selected subset (phase-II) of a larger (phase-I) study. Efficient analysis of the resulting data set combining disparate information from phase-I and phase-II, however, can be complex. Most of the existing methods, including semiparametric maximum-likelihood estimator, require the information in phase-I to be summarized into a fixed number of strata.

Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3.

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations.

Individual and community-level risk for COVID-19 mortality in the United States.

Reducing COVID-19 burden for populations will require equitable and effective risk-based allocations of scarce preventive resources, including vaccinations. To aid in this effort, we developed a general population risk calculator for COVID-19 mortality based on various sociodemographic factors and pre-existing conditions for the US population, combining information from the UK-based OpenSAFELY study with mortality rates by age and ethnicity across US states. We tailored the tool to produce absolute risk estimates in future time frames by incorporating information on pandemic dynamics at the community level.

Quantifying the Predictive Performance of Objectively Measured Physical Activity on Mortality in the UK Biobank.

Background: Objective measures of physical activity (PA) derived from wrist-worn accelerometers are compared with traditional risk factors in terms of mortality prediction performance in the UK Biobank.

Method: A subset of participants in the UK Biobank study wore a tri-axial wrist-worn accelerometer in a free-living environment for up to 7 days. A total of 82 304 individuals over the age of 50 (439 707 person-years of follow-up, 1959 deaths) had both accelerometry data that met specified quality criteria and complete data on a set of traditional mortality risk factors.

Combined Utility of 25 Disease and Risk Factor Polygenic Risk Scores for Stratifying Risk of All-Cause Mortality.

While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.

Isolated Diastolic Hypertension in the UK Biobank: Comparison of ACC/AHA and ESC/NICE Guideline Definitions.

The 2017 American College of Cardiology/American Heart Association guideline defines hypertension as a blood pressure ≥130/80 mm Hg, whereas the 2018 European Society of Cardiology (ESC) and 2019 National Institute for Health and Care Excellence (NICE) guidelines use a ≥140/90 mm Hg threshold. Our objective was to study the associations between isolated diastolic hypertension (IDH), diagnosed using these 2 blood pressure thresholds, and cardiovascular disease (CVD) in a large cohort of UK adults. We analyzed data from UK Biobank, which enrolled participants between 2006 and 2010 with follow-up through March 2019.

Amplification of explosive width in complex networks.

We present an adaptive coupling strategy to induce hysteresis/explosive synchronization in complex networks of phase oscillators (Sakaguchi-Kuramoto model). The coupling strategy ensures explosive synchronization with significant explosive width enhancement. Results show the robustness of the strategy, and the strategy can diminish (by inducing enhanced hysteresis loop) the contrarian impact of phase frustration in the network, irrespective of the network structure or frequency distributions.

Case-Only Analysis of Gene-Environment Interactions Using Polygenic Risk Scores.

Investigations of gene (G)-environment (E) interactions have led to limited findings to date, possibly due to weak effects of individual genetic variants. Polygenic risk scores (PRS), which capture the genetic susceptibility associated with a set of variants, can be a powerful tool for detecting global patterns of interaction. Motivated by the case-only method for evaluating interactions with a single variant, we propose a case-only method for the analysis of interactions with a PRS in case-control studies.

Generalized meta-analysis for multiple regression models across studies with disparate covariate information.

Meta-analysis is widely popular for synthesizing information on common parameters of interest across multiple studies because of its logistical convenience and statistical efficiency. We develop a generalized meta-analysis approach to combining information on multivariate regression parameters across multiple studies that have varying levels of covariate information. Using algebraic relationships among regression parameters in different dimensions, we specify a set of moment equations for estimating parameters of a maximal model through information available from sets of parameter estimates for a series of reduced models from the different studies.

Diffusion dynamics of a conductance-based neuronal population.

We study the spatiotemporal dynamics of a conductance-based neuronal cable. The processes of one-dimensional (1D) and 2D diffusion are considered for a single variable, which is the membrane voltage. A 2D Morris-Lecar (ML) model is introduced to investigate the nonlinear responses of an excitable conductance-based neuronal cable.

Synchronization transition in Sakaguchi-Kuramoto model on complex networks with partial degree-frequency correlation.

We investigate transition to synchronization in the Sakaguchi-Kuramoto (SK) model on complex networks analytically as well as numerically. Natural frequencies of a percentage (f) of higher degree nodes of the network are assumed to be correlated with their degrees and that of the remaining nodes are drawn from some standard distribution, namely, Lorentz distribution. The effects of variation of f and phase frustration parameter α on transition to synchronization are investigated in detail.

Transition to synchrony in degree-frequency correlated Sakaguchi-Kuramoto model.

We investigate transition to synchrony in degree-frequency correlated Sakaguchi-Kuramoto (SK) model on complex networks both analytically and numerically. We analytically derive self-consistent equations for group angular velocity and order parameter for the model in the thermodynamic limit. Using the self-consistent equations we investigate transition to synchronization in SK model on uncorrelated scale-free (SF) and Erdős-Rényi (ER) networks in detail.