A study of the pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed pregnant women with HIV.

OBJECTIVE: The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy. DESIGN: An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1. METHODS: Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates ( n  = 29) were followed from birth to 4-8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated. RESULTS: Mean areas under the concentration-time curve over the dosing interval (AUC tau ) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUC tau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUC tau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission. CONCLUSION: Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.

Emergency powers and the pandemic: Reflecting on state legislative reforms and the future of public health response.

The first 2 years of combatting the COVID-19 pandemic necessitated an unprecedented use of emergency powers. States responded with an equally unprecedented flurry of legislative changes to the legal underpinnings of emergency response and public health authorities. In this article, we provide a brief background on the framework and use of governors and state health officials' emergency powers. We then analyze several key themes, including both the enhancement and restriction of powers, emerging from emergency management and public health legislation introduced in state and territorial legislatures. During the 2020 and 2021 state and territorial legislative sessions, we tracked legislation related to the emergency powers of governors and state health officials. Legislators introduced hundreds of bills impacting these powers, some enhancing and others restricting emergency powers. Enhancements included increasing vaccine access and expanding the pool of eligible medical professions that could administer vaccinations, strengthening public health investigation and enforcement authority for state agencies, and preclusion of local orders by orders at the state level. Restrictions included establishing oversight mechanisms for executive actions, limits on the duration of the emergency, limiting the scope of emergency powers allowed during a declared emergency, and other restraints. By -describing these legislative trends, we hope to inform governors, state health officials, -policymakers, and emergency managers about how changes in the law may impact future public health and emergency response capabilities. Understanding this new legal landscape is critical to effectively preparing for future threats.

Architecture of a Data Portal for Publishing and Delivering Open Data for Atmospheric Measurement.

Atmospheric data are collected by researchers every day. Campaigns such as GOAmazon 2014/2015 and the Amazon Tall Tower Observatory collect essential data on aerosols, gases, cloud properties, and meteorological parameters in the Brazilian Amazon basin. These data products provide insights and essential information for analyzing and predicting natural processes. However, in Brazil, it is estimated that more than 80% of the scientific data collected are not published due to the lack of web portals that collect and store these data. This makes it difficult, or even impossible, to access and integrate the data, which can result in the loss of significant amounts of information and significantly affect the understanding of the overall data. To address this problem, we propose a data portal architecture and open data deployment that enable Big Data processing, human interaction, and download-oriented approaches with tools that help users catalog, publish and visualize atmospheric data. Thus, we describe the architecture developed, based on the experience of the Atmospheric Radiation Measurement Data Center, which incorporates the principles of FAIR, the infrastructure and content management system for managing scientific data. The portal partial results were tested with environmental data from contaminated areas at the University of São Paulo. Overall, this data portal creates more shared knowledge about atmospheric processes by providing users with access to open environmental data.

The mediating role of vaccine hesitancy in the relations of COVID-19 conspiracy beliefs and vaccination outcomes: Which dimensions matter?

COVID-19 conspiracy beliefs have a powerful detrimental influence on COVID-19 vaccine perceptions and behaviors. We investigate an expanded range of outcomes for COVID-19 conspiracy beliefs, and we test which vaccine hesitancy dimensions mediate these relations. Our results show that COVID-19 conspiracy beliefs relate to COVID-19 vaccination willingness and receipt, flu vaccination willingness and receipt, as well as vaccine word-of-mouth. Many of these relations are mediated by vaccine hesitancy dimensions that represent perceptions that vaccines pose health risks as well as perceptions that vaccines are not needed because the respondent is healthy. Our discussion identifies directions for future research.

Increased nitrogen use efficiency in crop production can provide economic and environmental benefits.

Potential economic and environmental benefits of increasing nitrogen-use efficiency (NUE) are widely recognized but scarcely quantified. This study quantifies the effects of increased NUE on 1) the national agricultural economy using a simulation model of US agriculture and 2) regional water quality effects using a biogeochemical model for the Arkansas-White-Red river basin. National economic effects are reported for NUE improvement scenarios of 10%, 20%, 50%, and 100%, whereas regional water quality effects are estimated for a 20% NUE improvement scenario in the Arkansas-White-Red river basin. Simulating a 20% increase in NUE in row crops is shown to reduce N requirements by 1.4 million tonnes y-1 and increase farmer net profits by 1.6% ($743 million) per year by 2026 over the baseline simulation for the same period. For each 10% increase in NUE, annual farm revenues for commodity crops increased over the baseline by approximately $350 million per year by 2026. Changes in crop prices and land-use relative to the baseline were less than 2%. This suggests a net benefit even though fertilizer cost savings can result in increased cultivation of land, i.e., 'Jevon's paradox'. Results from the biogeochemical model of the Arkansas-White-Red river basin suggest that a 20% increase in NUE corresponds to a 5.72% reduction in nitrate loadings to freshwaters, with higher reductions in agricultural watersheds. The value of these reductions was estimated as $43 ha-1, for a total of $15.3 to 136.7 million yr-1 in avoided water treatment costs. After estimating the social value of increased NUE, we conclude with a discussion of potential strategies to increase efficiency and the research needed to achieve this goal. These include perennialization of the agricultural landscape, genetic crop improvement, targeted fertilizer application, and manipulation of the plant-root microbiome.

Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status.

BACKGROUND: Asthma prevalence is 339 million globally. 'Severe asthma' (SA) comprises subjects with uncontrolled asthma despite proper management. OBJECTIVES: To compare asthma from diverse ethnicities and environments. METHODS: A cross-sectional analysis of two adult cohorts, a Brazilian (ProAR) and a European (U-BIOPRED). U-BIOPRED comprised of 311 non-smoking with Severe Asthma (SAn), 110 smokers or ex-smokers with SA (SAs) and 88 mild to moderate asthmatics (MMA) while ProAR included 544 SA and 452 MMA. Although these projects were independent, there were similarities in objectives and methodology, with ProAR adopting operating procedures of U-BIOPRED. RESULTS: Among SA subjects, age, weight, proportion of former smokers and FEV1 pre-bronchodilator were similar. The proportion of SA with a positive skin prick tests (SPT) to aeroallergens, the scores of sino-nasal symptoms and quality of life were comparable. In addition, blood eosinophil counts (EOS) and the % of subjects with EOS > 300 cells/µl were not different. The Europeans with SA however, were more severe with a greater proportion of continuous oral corticosteroids (OCS), worse symptoms and more frequent exacerbations. FEV1/FVC pre- and post-bronchodilator were lower among the Europeans. The MMA cohorts were less comparable in control and treatment, but similar in the proportion of allergic rhinitis, gastroesophageal reflux disease and EOS >3%. CONCLUSIONS: ProAR and U-BIOPRED cohorts, with varying severity, ethnicity and environment have similarities, which provide the basis for global external validation of asthma phenotypes. This should stimulate collaboration between asthma consortia with the aim of understanding SA, which will lead to better management.

Child Support Conviction and Recidivism: A Statistical Interaction Pattern by Race.

An estimated 50,000 parents are behind bars on average daily for child support nonpayment, but information about these fathers and their recidivism rates are lacking. Using a jail sample (N = 16,382), multinomial logistics regression method was utilized; subgroup analysis was used to investigate differential beta weights of predictor variables. Informed by Critical Race Theory, findings showed that fathers incarcerated for arrears had significantly higher rates of recidivism than other jailed men, but had an interaction effect with race. After controlling for age, education, and prior attendance at 12-step meetings, Black fathers but NOT White fathers showed significant post-release recidivism. Implications are discussed.

Multiple opportunities for creating sanctuary.

This article describes the experience of five change agents from a diverse group of settings: two residential treatment programs for children and adolescents, a group home for disturbed adolescents, a residential substance abuse program for urban women, and an acute care psychiatric inpatient unit. What all of these innovators share is a willingness to engage in the challenging and complex process of changing their systems to better address the needs of the traumatized children, adolescents, and adults who populate their various programs. Using the Sanctuary Model as originally applied to a specialty inpatient psychiatric program for adult survivors of childhood abuse as their guide, the leaders of each of these organizations discuss the process of change that they are directing.