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The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2 SNP ) for European-American females of 29% that is similar to h2 SNP for schizophrenia and is substantially higher than h2 SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD--for both European- and African-American individuals--and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Digital health interventions could be a scalable approach to delivering at-home COVID-19 testing. SCALE-UP II aimed to investigate the effectiveness of three digital health interventions on the delivery of mailed at-home COVID-19 testing: text messaging (TM), automated chatbot (CA), and patient navigation upon request (PN). Pragmatic randomized controlled trial. Participants who self-reported that they had a smartphone were randomized in a 2x2x2 factorial design (Smartphone study) to receive (i) chatbot or TM; (ii) option to request PN; and (iii) intervention frequency every 10 or 30 days. All other participants were randomized in a 2x2 factorial design (Non-Smartphone study) to receive (i) option to request PN; and (ii) intervention frequency every 10 or 30 days. Study settings were safety net community health centers (CHCs) located across the state of Utah, USA. Eligible patients were >18 years old, with a primary care visit in the last three years, and a valid cellphone in the CHC electronic health record. The primary outcome was proportion of participants requesting at-home COVID-19 tests. The trial enrolled 2,117 in the Smartphone study and 31,439 in the Non-Smartphone study. In the Smartphone study, the proportion of participants who requested test kits in the Chatbot arm was lower than in TM (16.6% vs. 52.1%, aRR=0.317 [98.33% CI 0.27-0.38], P<.0001). In the Non-Smartphone study, the proportion of participants who requested test kits was higher if they were messaged every 10 days rather than every 30 days (5.5% vs 4.8%, aRR=1.144 [97.5% CI 1.03-1.28], P=.005). Yet, participants in the 10-day vs. 30-day condition were more likely to opt out of receiving study interventions (12.6% vs 7.3%, aRR=1.72 [97.5% CI 1.59-1.86], P<.0001). In the Non-Smartphone study, the proportion of participants who requested test kits was lower for those in the PN condition compared to No PN (4.3% vs 5.9%, aRR=0.729 [97.5% CI 0.65-0.81], P<.0001). Simple bidirectional TM was more effective than an interactive Web-based chatbot on the delivery of COVID-19 testing. Although messaging every 10 days was more effective than every 30 days, it also led to a larger opt-out rate. Digital health interventions based on automated bidirectional text messaging is a simple, scalable, and low-cost strategy to offer access to at-home COVID-19 testing. Similar approaches may be used to support public health response and other forms of at-home testing. Clinicaltrials.gov (NCT05533918 and NCT05533359). RR2-doi: 10.1136/bmjopen-2023-081455.

Observations and models agree that the Greenland Ice Sheet (GrIS) surface mass balance (SMB) has decreased since the end of the 1990s due to an increase in meltwater runoff and that this trend will accelerate in the future. However, large uncertainties remain, partly due to different approaches for modelling the GrIS SMB, which have to weigh physical complexity or low computing time, different spatial and temporal resolutions, different forcing fields, and different ice sheet topographies and extents, which collectively make an inter-comparison difficult. Our GrIS SMB model intercomparison project (GrSMBMIP) aims to refine these uncertainties by intercomparing 13 models of four types which were forced with the same ERA-Interim reanalysis forcing fields, except for two global models. We interpolate all modelled SMB fields onto a common ice sheet mask at 1 km horizontal resolution for the period 1980–2012 and score the outputs against (1) SMB estimates from a combination of gravimetric remote sensing data from GRACE and measured ice discharge; (2) ice cores, snow pits and in situ SMB observations; and (3) remotely sensed bare ice extent from MODerate-resolution Imaging Spectroradiometer (MODIS). Spatially, the largest spread among models can be found around the margins of the ice sheet, highlighting model deficiencies in an accurate representation of the GrIS ablation zone extent and processes related to surface melt and runoff. Overall, polar regional climate models (RCMs) perform the best compared to observations, in particular for simulating precipitation patterns. However, other simpler and faster models have biases of the same order as RCMs compared with observations and therefore remain useful tools for long-term simulations or coupling with ice sheet models. Finally, it is interesting to note that the ensemble mean of the 13 models produces the best estimate of the present-day SMB relative to observations, suggesting that biases are not systematic among models and that this ensemble estimate can be used as a reference for current climate when carrying out future model developments. However, a higher density of in situ SMB observations is required, especially in the south-east accumulation zone, where the model spread can reach 2 m w.e. yr−1 due to large discrepancies in modelled snowfall accumulation.

In May 2013, a revised and updated version of the Centers for Disease Control and Prevention/National Institutes of Health/HIV Medicine Association Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents was released online. These guidelines, since their inception in 1989, have been widely accessed in the United States and abroad. These guidelines have focused on the management of HIV/AIDS-related opportunistic infections that occur in the United States. In other parts of the world, the spectrum of complications may be different and the resources available for diagnosis and management may not be identical to those in the United States. The sections that have been most extensively updated are those on immune reconstitution inflammatory syndrome, tuberculosis, hepatitis B, hepatitis C, human papillomavirus, and immunizations. The guidelines will not be published in hard copy form. This document will be revised as needed throughout each year as new data become available.

Background. The potential for aerosol transmission of infectious influenza virus (ie, in healthcare facilities) is controversial. We constructed a simulated patient examination room that contained coughing and breathing manikins to determine whether coughed influenza was infectious and assessed the effectiveness of an N95 respirator and surgical mask in blocking transmission. Methods. National Institute for Occupational Safety and Health aerosol samplers collected size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin, beside the mouth, and at 3 other locations in the room. Total recovered virus was quantitated by quantitative polymerase chain reaction and infectivity was determined by the viral plaque assay and an enhanced infectivity assay. Results. Infectious influenza was recovered in all aerosol fractions (5.0% in >4 μm aerodynamic diameter, 75.5% in 1—4 μm, and 19.5% in <1 μm; n = 5). Tightly sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked 64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious virus (n = 2). Conclusions. These results support a role for aerosol transmission and represent the first reported laboratory study of the efficacy of masks and respirators in blocking inhalation of influenza in aerosols. The results indicate that a poorly fitted respirator performs no better than a loosely fitting mask.

Between 15 and 19 March 2022, East Antarctica experienced an exceptional heat wave with widespread 30°–40°C temperature anomalies across the ice sheet. This record-shattering event saw numerous monthly temperature records being broken including a new all-time temperature record of −9.4°C on 18 March at Concordia Station despite March typically being a transition month to the Antarctic coreless winter. The driver for these temperature extremes was an intense atmospheric river advecting subtropical/midlatitude heat and moisture deep into the Antarctic interior. The scope of the temperature records spurred a large, diverse collaborative effort to study the heat wave’s meteorological drivers, impacts, and historical climate context. Here we focus on describing those temperature records along with the intricate meteorological drivers that led to the most intense atmospheric river observed over East Antarctica. These efforts describe the Rossby wave activity forced from intense tropical convection over the Indian Ocean. This led to an atmospheric river and warm conveyor belt intensification near the coastline, which reinforced atmospheric blocking deep into East Antarctica. The resulting moisture flux and upper-level warm-air advection eroded the typical surface temperature inversions over the ice sheet. At the peak of the heat wave, an area of 3.3 million km 2 in East Antarctica exceeded previous March monthly temperature records. Despite a temperature anomaly return time of about 100 years, a closer recurrence of such an event is possible under future climate projections. In Part II we describe the various impacts this extreme event had on the East Antarctic cryosphere.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Between 15 and 19 March 2022, East Antarctica experienced an exceptional heat wave with widespread 30°–40°C temperature anomalies across the ice sheet. In Part I, we assessed the meteorological drivers that generated an intense atmospheric river (AR) that caused these record-shattering temperature anomalies. Here, we continue our large collaborative study by analyzing the widespread and diverse impacts driven by the AR landfall. These impacts included widespread rain and surface melt that was recorded along coastal areas, but this was outweighed by widespread high snowfall accumulations resulting in a largely positive surface mass balance contribution to the East Antarctic region. An analysis of the surface energy budget indicated that widespread downward longwave radiation anomalies caused by large cloud-liquid water contents along with some scattered solar radiation produced intense surface warming. Isotope measurements of the moisture were highly elevated, likely imprinting a strong signal for past climate reconstructions. The AR event attenuated cosmic ray measurements at Concordia, something previously never observed. Last, an extratropical cyclone west of the AR landfall likely triggered the final collapse of the critically unstable Conger Ice Shelf while further reducing an already record low sea ice extent.