Conceptual framework and rationale

The sterile insect technique (SIT) has been shown to be an effective and sustainable genetic approach to control populations of selected major pest insects, when part of area-wide integrated pest management (AW-IPM) programmes. The technique introduces genetic sterility in females of the target population in the field following their mating with released sterile males. This process results in population reduction or elimination via embryo lethality caused by dominant lethal mutations induced in sperm of the released males. In the past, several field trials have been carried out for mosquitoes with varying degrees of success. New technology and experience gained with other species of insect pests has encouraged a reassessment of the use of the sterility principle as part of integrated control of malaria vectors. Significant technical and logistic hurdles will need to be overcome to develop the technology and make it effective to suppress selected vector populations, and its application will probably be limited to specific ecological situations. Using sterile males to control mosquito vector populations can only be effective as part of an AW-IPM programme. The area-wide concept entails the targeting of the total mosquito population within a defined area. It requires, therefore, a thorough understanding of the target pest population biology especially as regards mating behaviour, population dynamics, dispersal and level of reproductive isolation. The key challenges for success are: 1) devising methods to monitor vector populations and measuring competitiveness of sterile males in the field, 2) designing mass rearing, sterilization and release strategies that maintain competitiveness of the sterile male mosquitoes, 3) developing methods to separate sexes in order to release only male mosquitoes and 4) adapting suppression measures and release rates to take into account the high reproductive rate of mosquitoes. Finally, success in area-wide implementation in the field can only be achieved if close attention is paid to political, socio-economic and environmental sensitivities and an efficient management organization is established taking into account the interests of all potential stakeholders of an AW-IPM programme

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Physical properties of the WAIS Divide ice core

The WAIS (West Antarctic Ice Sheet) Divide deep ice core was recently completed to a total depth of 3405 m, ending ~50 m above the bed. Investigation of the visual stratigraphy and grain characteristics indicates that the ice column at the drilling location is undisturbed by any large-scale overturning or discontinuity. The climate record developed from this core is therefore likely to be continuous and robust. Measured grain-growth rates, recrystallization characteristics, and grain-size response at climate transitions fit within current understanding. Significant impurity control on grain size is indicated from correlation analysis between impurity loading and grain size. Bubble-number densities and bubble sizes and shapes are presented through the full extent of the bubbly ice. Where bubble elongation is observed, the direction of elongation is preferentially parallel to the trace of the basal (0001) plane. Preferred crystallographic orientation of grains is present in the shallowest samples measured, and increases with depth, progressing to a vertical-girdle pattern that tightens to a vertical single-maximum fabric. This single-maximum fabric switches into multiple maxima as the grain size increases rapidly in the deepest, warmest ice. A strong dependence of the fabric on the impurity- mediated grain size is apparent in the deepest samples

Safeguarding Asian tapir habitat in Sumatra, Indonesia

The Asian tapir Tapirus indicus is the only tapir species in Southeast Asia. It is declining across its range and is categorized as Endangered on the IUCN Red List. The forests of Sumatra are critical to Asian tapir conservation as they contain some of the last remaining populations of the species, yet conservation efforts are hindered by a lack of information on habitat suitability. We collated camera-trap data from nine landscapes across 69,500 km2 of Sumatran rainforest to help predict suitable habitat for Asian tapirs on the island. Predictions from Bayesian occupancy models demonstrated that tapir occupancy was greatest in forests below 600 m elevation and exclusively in forests with high aboveground biomass. Forests around the Barisan Mountains on the west of Sumatra provide the most suitable habitat for the species. Only 36% of the most critical habitat (i.e. the top 20th percentile of predicted occupancy) for tapirs is formally protected for conservation, with much of the remainder found in forests allocated to watershed protection (35%) or logging (23%). We highlight several key areas in Sumatra where tapir conservation could be bolstered, such as by leveraging existing conservation efforts for other charismatic flagships species on the island

Effectiveness of 20 years of conservation investments in protecting orangutans

Conservation strategies are rarely systematically evaluated, which reduces transparency, hinders the cost-effective deployment of resources, and hides what works best in different contexts. Using data on the iconic and critically endangered orangutan (Pongo spp.), we developed a novel spatiotemporal framework for evaluating conservation investments. We show that around USD 1 billion was invested between 2000 and 2019 into orangutan conservation by governments, non-governmental organizations, companies and communities. Broken down by allocation to different conservation strategies, we find that habitat protection, patrolling and public outreach had the greatest return-on-investment for maintaining orangutan populations. Given variability in threats, land-use opportunity costs, and baseline remunerations in different regions, there were differential benefits-per-dollar invested across conservation activities and regions. We show that, while challenging from a data and analysis perspective, it is possible to fully understand the relationships between conservation investments and outcomes, and the external factors that influence these outcomes. Such analyses can provide improved guidance towards more effective biodiversity conservation. Insights into the spatiotemporal interplays between the costs and benefits driving effectiveness can inform decisions about the most suitable orangutan conservation strategies for halting population declines. While our study focuses on the three extant orangutan species of Sumatra and Borneo, our findings have broad application for evidence-based conservation science and practice worldwide