Evaluation of BCRP-Related DDIs Between Methotrexate and Cyclosporin A Using Physiologically Based Pharmacokinetic Modelling.

Background And Objective: This study provides a physiologically based pharmacokinetic (PBPK) model-based analysis of the potential drug-drug interaction (DDI) between cyclosporin A (CsA), a breast cancer resistance protein transporter (BCRP) inhibitor, and methotrexate (MTX), a putative BCRP substrate.

Methods: PBPK models for CsA and MTX were built using open-source tools and published data for both model building and for model verification and validation. The MTX and CsA PBPK models were evaluated for their application in simulating BCRP-related DDIs.

A Linguistic-Sensorimotor Model of the Basic-Level Advantage in Category Verification.

People are generally more accurate at categorizing objects at the basic level (e.g., dog) than at more general, superordinate categories (e.

Parametric analysis on the global design of flexible riser under different environmental conditions using OrcaFlex.

The application of flexible risers has led to increased production of fluid contents in the marine industry. This paper presents the design challenges of a flexible riser subjected to internal pressure under deep-water conditions, at a water depth of 2000 m. Parametric variations with extensive dynamic analysis were carried out.

Influence of age and sex on the diagnostic yield of inherited cardiac conditions in sudden arrhythmic death syndrome decedents.

Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods And Results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included.

SPE-CZE-MS quantifies zeptomole concentrations of phosphorylated peptides.

Capillary zone electrophoresis (CZE) is gaining attention in the field of single-cell proteomics for its ultra-low-flow and high-resolution separation abilities. Even more sample-limited yet rich in biological information are phosphoproteomics experiments, as the phosphoproteome composes only a fraction of the whole cellular proteome. Rapid analysis, high sensitivity, and maximization of sample utilization are paramount for single-cell analysis.

A Preplanned Multi-Stage Platform Trial for Discovering Multiple Superior Treatments With Control of FWER and Power.

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed superiority. In such trials, it can be important to ensure that error rates are controlled. This paper introduces a multi-stage design that enables the addition of new treatment arms, at any point, in a preplanned manner within a platform trial, while still maintaining control over the family-wise error rate.

Preliminary evidence that self-incentives uniquely promote smoking cessation in incarcerated populations: A pilot randomized controlled trial.

Introduction: Smoking prevalence rates in prison are typically four times higher than the rates found within community-based settings, increasing premature mortality. Encouraging smokers to self-administer incentives contingent on abstinence (i.e.

Decision-making about palliative sedation for patients with cancer: a qualitative study in five European countries linked to the Palliative sedation project.

Background: Palliative sedation refers to the proportional use of titrated medication which reduces consciousness with the aim of relieving refractory suffering related to physical and psychological symptoms and/or existential distress near the end of life. Palliative sedation is intended to be an end of life option that enables healthcare professionals to provide good patient care but there remains controversy on how it is used. Little is known about decision-making processes regarding this procedure.

Regulatory preparedness for multicomponent nanomaterials: Current state, gaps and challenges of REACH.

In 2018 the European Commission adopted revisions to the Annexes of Regulation (EC) No 1907/2006 concerning registration, evaluation, authorisation and restriction of chemicals (REACH) to introduce nanomaterial-specific clarifications and provisions. Multicomponent nanomaterial (MCNM) is a non-regulatory term that has been used in recent EU-funded projects to describe nanomaterials with a complex structure and/or composition and which are expected to be increasingly used in products in the near future. This paper examines the regulatory preparedness of REACH, and its revised Annexes, for MCNMs.

Cervical ripening at home or in hospital during induction of labour: the CHOICE prospective cohort study, process evaluation and economic analysis.

Background: Around one in three pregnant women undergoes induction of labour in the United Kingdom, usually preceded by in-hospital cervical ripening to soften and open the cervix.

Objectives: This study set out to determine whether cervical ripening at home is within an acceptable safety margin of cervical ripening in hospital, is effective, acceptable and cost-effective from both National Health Service and service user perspectives.

Design: The CHOICE study comprised a prospective multicentre observational cohort study using routinely collected data (CHOICE cohort), a process evaluation comprising a survey and nested case studies (qCHOICE) and a cost-effectiveness analysis.

Finding order in chaos: influences of environmental complexity and predictability on development.

Environments are dynamic and complex. Some children experience more predictable early life environments than others. Here, we consider how moment-by-moment complexity and predictability in our early environments influence development.

Response of South Asia PM pollution to ammonia emission changes and associated impacts on human health.

Countries in South Asia are suffering severe PM pollution with rapid economic development, impacting human health and the environment. Whilst much attention has been given to understanding the contribution of primary emissions, the contribution of agriculture to PM concentrations, especially from agricultural ammonia (NH) emissions, remains less explored. Using an advanced regional atmospheric chemistry and transport modelling system (WRF-EMEP) with a new estimate of anthropogenic NH emissions inputs, we estimate the influence of agricultural NH emissions on surface PM in South Asia and evaluate the health impacts and the economic losses attributable to PM in 2018.

Creation of root cause analysis and action (RCA) standard work by a multidisciplinary team to prevent harm, reduce bias, and improve safety culture.

This project aimed to (1) develop a multidisciplinary team to rapidly conduct event analysis, (2) create tools to standardize event communication, (3) expand resiliency support provided to staff, and (4) decrease cycle time between event occurrence and action implementation. A multidisciplinary team was created to investigate safety events. The team developed standard work including key stakeholder notification of the event, a huddle to facilitate immediate mitigation of risk, staff resiliency support, a consistent interview approach, analysis of investigation data, and an accountability meeting to ensure consensus on steps required to prevent future harm.

SARTAB, a scalable system for automated real-time behavior detection based on animal tracking and Region Of Interest analysis: validation on fish courtship behavior.

Methods from Machine Learning (ML) and Computer Vision (CV) have proven powerful tools for quickly and accurately analyzing behavioral recordings. The computational complexity of these techniques, however, often precludes applications that require real-time analysis: for example, experiments where a stimulus must be applied in response to a particular behavior or samples must be collected soon after the behavior occurs. Here, we describe SARTAB (Scalable Automated Real-Time Analysis of Behavior), a system that achieves automated real-time behavior detection by continuously monitoring animal positions relative to behaviorally relevant Regions Of Interest (ROIs).

Unraveling Hydration Shell Dynamics and Viscosity Effects Around Cyanamide Probes via 2D IR Spectroscopy.

Hydration dynamics and solvent viscosity play critical roles in the structure and function of biomolecules. An overwhelming body of evidence suggests that protein and membrane fluctuations are closely linked to solvent fluctuations. While extensive research exists on the use of vibrational probes to detect local interactions and solvent dynamics, fewer studies have explored how the behavior of these reporters changes in response to bulk viscosity.

Dynamic human gut microbiome and immune shifts during an immersive psychosocial intervention program.

Background: Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

Method: To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 52 participants (M = 49.56, SD = 13.

Factors affecting women's access to primary care in the United States since the Affordable Care Act: A mixed-methods systematic review.

Background: In the United States, the Affordable Care Act (ACA) expanded public and private health coverage, increased health insurance affordability, reduced healthcare costs, and improved healthcare quality for many. Despite ACA provisions, lack of insurance and other factors continue to affect working-age women's access to primary care services.

Methods: We conducted a mixed-method systematic review to identify factors that affect women's access to primary care services since the ACA.

An Estimate of Preventable Harms Associated With Screening Colonoscopy Overuse in the U.S.

Introduction: Screening colonoscopy is often performed on patients who are younger or older than the ages specified in national guidelines or at shorter intervals than recommended. The annual incidence of harms associated with overuse of screening colonoscopy in the U.S.

Health impacts of climate change in the UK: A qualitative synthesis detailing the conjuncture of social structure, extreme weather, and mental health.

This qualitative synthesis explores the experiences of UK communities facing growing health risks from climate change and extreme weather. The eight included studies show the profound impacts of extreme weather events such as floods on mental health, including challenges to self-identity and anxiety from the fear of flooding returning. Included data reveal individual and household impacts of extreme weather are mediated by a complex interaction of institutional support, community support, gender inequalities and personal agency.