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Overall the process model contains 106 tasks and 78 decision points across all domains, with the largest number appearing in the circulation domain, followed by airway and breathing. A total of 34 deviations were observed across all 25 videos, and a maximum of 3 deviations were observed per video.

Overall, our data offered validity support for the blunt trauma primary survey process model. This process model was an important first step for the use of ABSM for the support of trauma care operations and team-based processes.

Overall, our data offered validity support for the blunt trauma primary survey process model. This process model was an important first step for the use of ABSM for the support of trauma care operations and team-based processes.

HIV self-testing (HIVST) offers a promising approach to increase HIV diagnosis and advance progress towards the UNAIDS 95-95-95 targets. We aimed to understand patterns of HIVST awareness and utilization in nine sub-Saharan African (SSA) countries, with the goal of identifying populations to target in disseminating this technology.

A cross-sectional study.

We pooled individual-level population-based data from nine Demographic and Health Surveys (DHS) in SSA conducted 2015-2019 (Burundi, Cameroon, Guinea, Malawi, Senegal, Sierra Leone, South Africa, Zambia, Zimbabwe). Primary outcomes were HIVST awareness and utilization. We used logistic regression with survey fixed effects to explore the relationship between sociodemographic characteristics and these outcomes. Adaptaquin Models were adjusted for sex, age, rural/urban residence, education, wealth, and marital status. We accounted for complex survey design.

The study sample included 177 572 people (66.0% women, mean age 29 ± 10 years), of whom 86.6% [95% confidence interval (95% CI) 86.4-86.7] were unaware of HIVST, 11.7% (95% CI 11.6-11.9) were aware of but never used HIVST, and 1.7% (95% CI 1.6-1.8) had used HIVST. In adjusted models, women were less likely to be aware of HIVST [odds ratio (OR) 0.75, 95% CI 0.71-0.79], but more likely to have used HIVST (OR 1.17, 95% CI 1.03-1.32) compared with men. Rural residents, those who were least educated, and poorest were less likely to have heard of or used HIVST.

HIVST awareness and uptake were low. Rural, less educated, and lower income populations were least likely to have heard of or used HIVST. Efforts to scale-up HIVST in these settings should aim to reach these less advantaged groups.

HIVST awareness and uptake were low. Rural, less educated, and lower income populations were least likely to have heard of or used HIVST. Efforts to scale-up HIVST in these settings should aim to reach these less advantaged groups.

Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV).

We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses.

Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4-15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses.

Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment.

Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment.

To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV.

We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS).

FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/μl, antiretroviral therapy, and HIV viral load.

There inform clinical practices of screening for frailty.

To evaluate the relationship between plasma biomarkers of systemic inflammation and incident age-related macular degeneration (AMD) in persons with the AIDS.

Case-control study.

Participants with incident intermediate-stage AMD (N = 26) in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and controls (N = 60) without AMD. Cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), and intestinal fatty acid-binding protein (I-FABP).

After adjustment for age, sex, and race/ethnicity, baseline mean ± standard deviation (SD) log10(mg/ml) plasma levels of CRP (0.52 ± 0.60 vs. 0.20 ± 0.43; P = 0.01) and mean ± SD log10(pg/ml) plasma levels of sCD14 (6.31 ± 0.11 vs. 6.23 ± 0.14; P = 0.008) were significantly higher among cases (incident AMD) than among controls (no AMD). There was a suggestion that mean ± SD baseline log10(pg/ml) plasma IL-6 levels (0.24 ± 0.33 vs. 0.11 ± 0.29; P = 0.10) might be higher among cases than controls. In a separate analysis of 548 participants in LSOCA, elevated baseline levels of plasma inflammatory biomarkers were associated with a greater risk of mortality but not with an increased risk of incident cataract.

These data suggest that systemic inflammatory biomarkers are associated with incident AMD but not incident cataract in persons with AIDS, and that systemic inflammation may play a role in the pathogenesis of AMD.

These data suggest that systemic inflammatory biomarkers are associated with incident AMD but not incident cataract in persons with AIDS, and that systemic inflammation may play a role in the pathogenesis of AMD.The relative susceptibility of people with HIV (PWH) to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is debated. Numerous studies have been published with apparently contradictory findings, but comparisons are difficult because they have been conducted in populations with different characteristics (e.g. age, prevalence comorbidities) and have used different comparison groups (e.g. HIV-negative cohorts, coronavirus disease 2019 (COVID-19) hospitalized patients, general population), and because of challenges to measure the most important confounders. Here, we review the evidence regarding risk and severity of SARS-CoV-2 infection in PWH compared with persons without HIV. Publications originate largely from high-income settings where the majority of the PWH are on antiretroviral therapy (ART). Despite early evidence supporting higher frequency of SARS-CoV-2 testing in PWH on ART, HIV infection is not associated with SARS-CoV-2 infection, once confounding by socioeconomic characteristic is taken into account. Most publications identify increased COVID-19 severity in PWH compared with people without HIV from the general population or compared with COVID-19 hospitalized patients. The only study with an adequate comparison group to reduce confounding, has not identified differences in COVID-19 disease severity by HIV. Publications consistently identify that COVID-19 severity in PWH is not homogeneous and increases with age and baseline comorbidities. As PWH have a higher prevalence of comorbidities than people without HIV, examining their respective contribution to poor health outcomes is not straight forward as comorbidities could mediate the effect of HIV on COVID-19 outcomes.Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger with an essential role in neuronal function. cAMP synthesis by adenylyl cyclases (AC) is controlled by G protein-coupled receptor (GPCR) signaling systems. However, the network of molecular players involved in the process is incompletely defined. Here, we used CRISPR/Cas9-based screening to identify that members of the potassium channel tetradimerization domain (KCTD) family are major regulators of cAMP signaling. Focusing on striatal neurons, we show that the dominant isoform KCTD5 exerts its effects through an unusual mechanism that modulates the influx of Zn2+ via the Zip14 transporter to exert unique allosteric effects on AC. We further show that KCTD5 controls the amplitude and sensitivity of stimulatory GPCR inputs to cAMP production by Gβγ-mediated AC regulation. Finally, we report that KCTD5 haploinsufficiency in mice leads to motor deficits that can be reversed by chelating Zn2+ Together, our findings uncover KCTD proteins as major regulators of neuronal cAMP signaling via diverse mechanisms.Planktonic organic matter forms the base of the marine food web, and its nutrient content (CNPorg) governs material and energy fluxes in the ocean. Over Earth history, CNPorg had a crucial role in marine metazoan evolution and global biogeochemical dynamics, but the geologic history of CNPorg is unknown, and it is often regarded constant at the "Redfield" ratio of ∼106161. We calculated CNPorg through Phanerozoic time by including nutrient- and temperature-dependent CNPorg parameterizations in a model of the long-timescale biogeochemical cycles. We infer a decrease from high Paleozoic CPorg and NPorg to present-day ratios, which stems from a decrease in the global average temperature and an increase in seawater phosphate availability. These changes in the phytoplankton's growth environment were driven by various Phanerozoic events specifically, the middle to late Paleozoic expansion of land plants and the Triassic breakup of the supercontinent Pangaea, which increased continental weatherability and the fluxes of weathering-derived phosphate to the oceans.

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