New approach methodologies to confirm developmental toxicity of pharmaceuticals based on weight of evidence.

The aim of embryo-fetal developmental toxicity assessments for pharmaceuticals is to inform potential risk of adverse pregnancy outcome, which has traditionally relied on studies in pregnant animals. Recent updates to international safety guidelines (ICH S5R3) have incorporated information on how to use weight of evidence and alternative assays to reduce animal use while still informing risk of fetal harm. Uptake of these alternative approaches has been slow due to limitations in understanding how alternative assays translate to in vivo effects and then relevance to human exposure.

Understanding the factors that influence stroke survivors to begin or resume exercise: a qualitative exploration.

Background: Exercise after stroke has the potential to increase survivors' physical function and decrease disability. However, despite health professional reporting they recommend exercise to stroke survivors, the majority are physically inactive. Stroke survivors have previously expressed a lack of adequate knowledge and skills to engage in exercise.

Brain Point of Care Ultrasound in Young Children Receiving Computed Tomography in the Emergency Department: A Proof of Concept Study.

: Point of Care Ultrasound (POCUS) is an important tool in pediatric emergency medicine. In neonatal intensive care medicine ultrasound is often used to evaluate the brains of sick neonates. In theory, POCUS could be used in the ED in young children to evaluate the brain for abnormal pathology.

Barriers to a Timely Diagnosis of Endometriosis: A Qualitative Systematic Review.

Objective: The diagnosis of endometriosis, a common gynecologic condition, is characterized by delays of up to 11 years. During this time, women may experience persistent symptoms that affect their quality of life, productivity, and relationships, and the disease may progress. It is therefore a priority to understand the factors that contribute to this delay to help improve the diagnostic pathway.

Preclinical Efficacy of the Antibody-Drug Conjugate CLDN6-23-ADC for the Treatment of CLDN6-Positive Solid Tumors.

Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6-23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker.

Incidence and risk factors for patellofemoral dislocation in adults with Charcot-Marie-Tooth disease: An observational study.

Background And Purpose: Patellofemoral (PF) dislocation is frequently encountered in clinical practice among people with Charcot-Marie-Tooth disease (CMT), but the frequency and risk factors for PF dislocation in adults with CMT are unknown. This study aimed to establish the incidence of PF dislocation in adults with CMT and to explore the risk factors associated with PF dislocation.

Methods: This is a cross-sectional study involving adults with a diagnosis of CMT, attending their outpatient clinics at a specialist neuromuscular centre in the United Kingdom.

Psychopathy and substance use predict recidivism in women: A 7-year prospective study.

Recidivism places a significant burden on society and efforts aimed at reducing cyclical criminal justice involvement are needed. This prospective study tested the utility of psychopathic traits in predicting general, felony, and substance-related rearrest in women following release from a correctional facility. The extent to which psychopathic traits offered incremental utility in predicting outcomes, above and beyond other established risk factors, including substance use disorder, was examined.

Functional delta residuals and applications to simultaneous confidence bands of moment based statistics.

Given a functional central limit (fCLT) for an estimator and a parameter transformation, we construct random processes, called functional delta residuals, which asymptotically have the same covariance structure as the limit process of the functional delta method. An explicit construction of these residuals for transformations of moment-based estimators and a multiplier bootstrap fCLT for the resulting functional delta residuals are proven. The latter is used to consistently estimate the quantiles of the maximum of the limit process of the functional delta method in order to construct asymptotically valid simultaneous confidence bands for the transformed functional parameters.

Acute appendicitis presenting with MIS-C secondary to COVID-19.

Acute Appendicitis (AA) is among the most common causes of abdominal pain in children. Several physical exam findings, scoring systems, and imaging studies, such as ultrasonography and computed tomography, exist to assist clinicians in diagnosing acute appendicitis. Despite multiple tools for assessing suspected acute appendicitis, it remains a challenge to diagnose acute appendicitis in the pediatric population.

Interventions for the prevention or treatment of epidural-related maternal fever: a systematic review and meta-analysis.

Background: Epidural-related maternal fever in women in labour has consequences for the mother and neonate. There has been no systematic review of preventive strategies.

Methods: RCTs evaluating methods of preventing or treating epidural-related maternal fever in women in active labour were eligible.

The expected behaviour of random fields in high dimensions: contradictions in the results of Bansal and Peterson [].

Bansal and Peterson (2018) found that in simple stationary Gaussian simulations Random Field Theory incorrectly estimates the number of clusters of a Gaussian field that lie above a threshold. Their results contradict the existing literature and appear to have arisen due to errors in their code. Using reproducible code we demonstrate that in their simulations Random Field Theory correctly predicts the expected number of clusters and therefore that many of their results are invalid.

Understanding mental health outcomes related to compassion fatigue in parents of children diagnosed with intellectual disability.

Background: Parenting a child diagnosed with intellectual disability includes a variety of stressors. The degree to which stress affects these parents has been given little emphasis. Compassion fatigue includes experiencing an emotional response to being unable to relieve the suffering of a loved one, burnout, strain and stress on the caregiver.

Inhibition of Acetyl-CoA Carboxylase Causes Malformations in Rats and Rabbits: Comparison of Mammalian Findings and Alternative Assays.

Acetyl-CoA carboxylase (ACC) is an enzyme within the de novo lipogenesis (DNL) pathway and plays a role in regulating lipid metabolism. Pharmacologic ACC inhibition has been an area of interest for multiple potential indications including oncology, acne vulgaris, metabolic diseases such as type 2 diabetes mellitus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. A critical role for ACC in de novo synthesis of long-chain fatty acids during fetal development has been demonstrated in studies in mice lacking Acc1, where the absence of Acc1 results in early embryonic lethality.

Impact of fibroblast growth factor receptor 1 (FGFR1) amplification on the prognosis of breast cancer patients.

Purpose: Various aberrations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3 are found in different cancers, including breast cancer (BC). This study analyzed the impact of FGFR amplification on the BC prognosis.

Methods: The study included 894 BC patients.

Assessment of the impact of implementation of a zero blood alcohol concentration law in Uruguay on moderate/severe injury and fatal crashes: a quasi-experimental study.

Background And Aims: Debates regarding lowering the blood alcohol concentration (BAC) limit for drivers are intensifying in the United States and other countries, and the World Health Organization recommends that the limit for adults should be 0.05%. In January 2016, Uruguay implemented a law setting a zero BAC limit for all drivers.

Associations between extracurricular activity participation and health-related variables in underrepresented children.

Background: Children from underrepresented populations exhibit low levels of physical activity (PA), diet quality, and health-related quality of life (QoL), but participation in extracurricular activities may positively impact these health outcomes.

Purpose: To examine differences in PA, dietary behavior, and QoL in underrepresented children by extracurricular activity dose (0, 1, ≥2) and type (sports, dance/martial arts, art/music).

Methods: Children (N = 754; Grades 4-6) completed the Physical Activity Questionnaire for Children, KidsScreen-27 (QoL), and the School Physical Activity and Nutrition Survey and self-reported extracurricular activity participation.

Long-Term Effects of Copper Nanopesticides on Soil and Sediment Community Diversity in Two Outdoor Mesocosm Experiments.

The use of novel pesticides containing nanomaterials (nanopesticides) is growing and is considered a promising approach to reduce the impacts of agriculture on the environment and human health. However, the environmental effects of these novel agrochemicals are not fully characterized, and more research is needed to determine the benefits and risks they confer. Here, we assessed the impacts of repeated exposures to a Cu(OH) nanopesticide on the soil and sediment biodiversity of target (terrestrial) and nontarget (wetland) ecosystems by performing long-term outdoor mesocosm experiments.

Locating Medical and Recreational Cannabis Outlets for Research Purposes: Online Methods and Observational Study.

Background: An increasing number of states have laws for the legal sale of recreational and medical cannabis out of brick-and-mortar storefront locations. Given the proliferation of cannabis outlets and their potential for impact on local economies, neighborhood structures, and individual patterns of cannabis use, it is essential to create practical and thorough methods to capture the location of such outlets for research purposes. However, methods used by researchers vary greatly between studies and often do not include important information about the retailer's license status and storefront signage.

Assessing Risk Among Correctional Community Probation Populations: Predicting Reoffense With Mobile Neurocognitive Assessment Software.

We seek to address current limitations of forensic risk assessments by introducing the first mobile, self-scoring, risk assessment software that relies on neurocognitive testing to predict reoffense. This assessment, run entirely on a tablet, measures decision-making via a suite of neurocognitive tests in less than 30 minutes. The software measures several cognitive and decision-making traits of the user, including impulsivity, empathy, aggression, and several other traits linked to reoffending.

Selective peak inference: Unbiased estimation of raw and standardized effect size at local maxima.

The spatial signals in neuroimaging mass univariate analyses can be characterized in a number of ways, but one widely used approach is peak inference: the identification of peaks in the image. Peak locations and magnitudes provide a useful summary of activation and are routinely reported, however, the magnitudes reflect selection bias as these points have both survived a threshold and are local maxima. In this paper we propose the use of resampling methods to estimate and correct this bias in order to estimate both the raw units change as well as standardized effect size measured with Cohen's d and partial R.

Price and product variation in Washington's recreational cannabis market.

Background: Ten U.S. states, Canada, and Uruguay have passed laws to legalize the production and sale of cannabis for non-medical purposes.