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HIV treatment has benefits to the patient, but does it decrease community HIV transmission as well? In this community-randomized trial in Zambia and South Africa, universal HIV testing with linkage to care and antiretroviral treatment according to local guidelines decreased HIV incidence.

piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1 , GTSF1 , GPAT2, MAEL, TDRD1 , and DDX4 . In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells. piRNAs are small RNA molecules found primarily in the testes of mice and men. Stallmeyer et al. demonstrate that variants in specific genes can disrupt the formation of piRNAs, impairing spermatogenesis and causing human male infertility.

Prediction of resting energy expenditure (pREE) using standardized formulas or bodyweight calculations often correlates poorly with measured REE (mREE) [3]. [...]our aim was to assess longitudinal mREE via indirect calorimetry (IC) in intubated COVID-19 patients. [...]we demonstrate progressive hypermetabolism and considerable variation in REE throughout ICU stay. CAS Article Google Scholar Download references Acknowledgements The primary authors acknowledge the commitment and many hundreds of hours spent conducting this trial by the study research coordinators, respiratory therapists, dietitians, critical care attendings, nurses, and other ICU staff at Duke University Hospital that made the many daily measurements in critically ill COIVD-19 patients possible. Only the authors and investigators at Duke University participated in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Background Alternative models for sustainable antiretroviral treatment (ART) delivery are necessary to meet the increasing demand to maintain population-wide ART for all people living with HIV (PLHIV) in sub-Saharan Africa. We undertook a review of published literature comparing health facility-based care (HFBC) with non-health facility based care (nHFBC) models of ART delivery in terms of health outcomes; viral suppression, loss to follow-up, retention and mortality. Methods We conducted a systematic search of Medline, Embase and Global Health databases from 2010 onwards. UNAIDS reports, WHO guidelines and abstracts from conferences were reviewed. All studies measuring at least one of the following outcomes, viral load suppression, loss-to-follow-up (LTFU) and mortality were included. Data were extracted, and a descriptive analysis was performed. Risk of bias assessment was done for all studies. Pooled estimates of the risk difference (for viral suppression) and hazard ratio (for mortality) were made using random-effects meta-analysis. Results Of 3082 non-duplicate records, 193 were eligible for full text screening of which 21 published papers met the criteria for inclusion. The pooled risk difference of viral load suppression amongst 4 RCTs showed no evidence of a difference in viral suppression (VS) between nHFBC and HFBC with an overall estimated risk difference of 1% [95% CI -1, 4%]. The pooled hazard ratio of mortality amongst 2 RCTs and 4 observational cohort studies showed no evidence of a difference in mortality between nHFBC and HFBC with an overall estimated hazard ratio of 1.01 [95% CI 0.88, 1.16]. Fifteen studies contained data on LTFU and 13 studies on retention. Although no formal quantitative analysis was performed on these outcomes due to the very different definitions between papers, it was observed that the outcomes appeared similar between HFBC and nHFBC. Conclusions Review of current literature demonstrates comparable outcomes for nHFBC compared to HFBC ART delivery programmes in terms of viral suppression, retention and mortality. PROSPERO number CRD42018088194 .

Challenges exist for assessing the impacts of climate and climate change on the hydrological cycle on local and regional scales, and in turn on water resources, food, energy, and natural hazards. Potential evapotranspiration (PET) represents atmospheric demand for water, which is required at high spatial and temporal resolutions to compute actual evapotranspiration and thus close the water balance near the land surface for many such applications, but there are currently no available high-resolution datasets of PET. Here we develop an hourly PET dataset (hPET) for the global land surface at 0.1° spatial resolution, based on output from the recently developed ERA5-Land reanalysis dataset, over the period 1981 to present. We show how hPET compares to other available global PET datasets, over common spatiotemporal resolutions and time frames, with respect to spatial patterns of climatology and seasonal variations for selected humid and arid locations across the globe. We provide the data for users to employ for multiple applications to explore diurnal and seasonal variations in evaporative demand for water. Measurement(s) evapotranspiration Technology Type(s) computational modeling technique Factor Type(s) temporal interval Sample Characteristic - Environment climate system • hydrological process Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15060387

Strong positive Indian Ocean Dipole (pIOD) events like those in 1997 and 2019 caused significant flooding in East Africa. While future projections indicate an increase in pIOD events, limited historical data hinders a comprehensive understanding of these extremes, particularly for unprecedented events. To overcome this we utilize a large ensemble of seasonal reforecast simulations, which show that regional rainfall continues to increase with pIOD magnitude, with no apparent limit. In particular we find that extreme rain days are highly sensitive to the pIOD index and their seasonal frequency increases super-linearly with higher pIOD magnitudes. It is vital that socio-economic systems and infrastructure are able to handle not only the increasing frequency of events like 1997 and 2019 but also unprecedented seasons of extreme rainfall driven by as-yet-unseen pIOD events. Future studies should prioritize understanding the hydrological implications and population exposure to these unprecedented extremes in East Africa.

Following childbirth, women need to stay sufficiently long in health facilities to receive adequate care. Little is known about length of stay following childbirth in low- and middle-income countries or its determinants. We described length of stay after facility delivery in 92 countries. We then created a conceptual framework of the main drivers of length of stay, and explored factors associated with length of stay in 30 countries using multivariable linear regression. Finally, we used multivariable logistic regression to examine the factors associated with stays that were \"too short\" (<24 h for vaginal deliveries and <72 h for cesarean-section deliveries). Across countries, the mean length of stay ranged from 1.3 to 6.6 d: 0.5 to 6.2 d for singleton vaginal deliveries and 2.5 to 9.3 d for cesarean-section deliveries. The percentage of women staying too short ranged from 0.2% to 83% for vaginal deliveries and from 1% to 75% for cesarean-section deliveries. Our conceptual framework identified three broad categories of factors that influenced length of stay: need-related determinants that required an indicated extension of stay, and health-system and woman/family dimensions that were drivers of inappropriately short or long stays. The factors identified as independently important in our regression analyses included cesarean-section delivery, birthweight, multiple birth, and infant survival status. Older women and women whose infants were delivered by doctors had extended lengths of stay, as did poorer women. Reliance on factors captured in secondary data that were self-reported by women up to 5 y after a live birth was the main limitation. Length of stay after childbirth is very variable between countries. Substantial proportions of women stay too short to receive adequate postnatal care. We need to ensure that facilities have skilled birth attendants and effective elements of care, but also that women stay long enough to benefit from these. The challenge is to commit to achieving adequate lengths of stay in low- and middle-income countries, while ensuring any additional time is used to provide high-quality and respectful care.

All women should have access to high quality maternity services—but what do we know about the health care available to and used by women? With a focus on low-income and middle-income countries, we present data that policy makers and planners can use to evaluate whether maternal health services are functioning to meet needs of women nationally, and potentially subnationally. We describe configurations of intrapartum care systems, and focus in particular on where, and with whom, deliveries take place. The necessity of ascertaining actual facility capability and providers' skills is highlighted, as is the paucity of information on maternity waiting homes and transport as mechanisms to link women to care. Furthermore, we stress the importance of assessment of routine provision of care (not just emergency care), and contextualise this importance within geographic circumstances (eg, in sparsely-populated regions vs dense urban areas). Although no single model-of-care fits all contexts, we discuss implications of the models we observe, and consider changes that might improve services and accelerate response to future challenges. Areas that need attention include minimisation of overintervention while responding to the changing disease burden. Conceptualisation, systematic measurement, and effective tackling of coverage and configuration challenges to implement high quality, respectful maternal health-care services are key to ensure that every woman can give birth without risk to her life, or that of her baby.

The University of British Columbia Nepal Expedition took place over several months in the fall of 2016 and was comprised of an international team of 37 researchers. This paper describes the objectives, study characteristics, organization and management of this expedition, and presents novel blood gas data during acclimatization in both lowlanders and Sherpa. An overview and framework for the forthcoming publications is provided. The expedition conducted 17 major studies with two principal goals-to identify physiological differences in: 1) acclimatization; and 2) responses to sustained high-altitude exposure between lowland natives and people of Tibetan descent. We performed observational cohort studies of human responses to progressive hypobaric hypoxia (during ascent), and to sustained exposure to 5050 m over 3 weeks comparing lowlander adults (n = 30) with Sherpa adults (n = 24). Sherpa were tested both with (n = 12) and without (n = 12) descent to Kathmandu. Data collected from lowlander children (n = 30) in Canada were compared with those collected from Sherpa children (n = 57; 3400-3900m). Studies were conducted in Canada (344m) and the following locations in Nepal: Kathmandu (1400m), Namche Bazaar (3440m), Kunde Hospital (3480m), Pheriche (4371m) and the Ev-K2-CNR Research Pyramid Laboratory (5050m). The core studies focused on the mechanisms of cerebral blood flow regulation, the role of iron in cardiopulmonary regulation, pulmonary pressures, intra-ocular pressures, cardiac function, neuromuscular fatigue and function, blood volume regulation, autonomic control, and micro and macro vascular function. A total of 335 study sessions were conducted over three weeks at 5050m. In addition to an overview of this expedition and arterial blood gas data from Sherpa, suggestions for scientists aiming to perform field-based altitude research are also presented. Together, these findings will contribute to our understanding of human acclimatization and adaptation to the stress of residence at high-altitude.

Equatorial East Africa (EEA) suffers from significant flood risks. These can be mitigated with preemptive action; however, currently available early warnings are limited to a few days’ lead time. Extending warnings using subseasonal climate forecasts could open a window for more extensive preparedness activity. However, before these forecasts can be used, the basis of their skill and relevance for flood risk must be established. Here we demonstrate that subseasonal forecasts are particularly skillful over EEA. Forecasts can skillfully anticipate weekly upper-quintile rainfall within a season, at lead times of 2 weeks and beyond. Wedemonstrate the link between the Madden–Julian oscillation (MJO) and extreme rainfall events in the region, and confirm that leading forecast models accurately represent the EEA teleconnection to the MJO. The relevance of weekly rainfall totals for fluvial flood risk in the region is investigated using a long record of streamflow from the Nzoia River in western Kenya. Both heavy rainfall and high antecedent rainfall conditions are identified as key drivers of flood risk, with upper-quintile weekly rainfall shown to skillfully discriminate flood events. We additionally evaluate GloFAS global flood forecasts for the Nzoia basin. Though these are able to anticipate some flooding events with several weeks lead time, analysis suggests action based on these would result in a false alarm more than 50% of the time. Overall, these results build on the scientific evidence base that supports the use of subseasonal forecasts in EEA, and activities to advance their use are discussed.