Sotatercept safety and effects on hemoglobin, bone, and vascular calcification

Introduction: Patients with end-stage kidney disease (ESKD) exhibit anemia, chronic kidney disease‒mineral bone disorder (CKD-MBD), and cardiovascular disease. The REN-001 and REN-002 phase II, multicenter, randomized studies examined safety, tolerability, and effects of sotatercept, an ActRIIA-IgG1 fusion protein trap, on hemoglobin concentration; REN-001 also explored effects on bone mineral density (BMD) and abdominal aortic vascular calcification. Methods: Forty-three patients were treated in REN-001 (dose range: sotatercept 0.3‒0.7 mg/kg or placebo subcutaneously [s.c.] for 200 days) and 50 in REN-002 (dose range: 0.1‒0.4 mg/kg i.v. and 0.13‒0.5 mg/kg s.c. for 99 days). Results: In REN-001, frequency of achieving target hemoglobin response (\u3e10 g/dl [6.21 mmol/l]) with sotatercept was dose-related and greater than placebo (0.3 mg/kg: 33.3%; 0.5 mg/kg: 62.5%; 0.7 mg/kg: 77.8%; 0.7 mg/kg [doses 1 and 2]/0.4 mg/kg [doses 3‒15]: 33.3%; placebo: 27.3%). REN-002 hemoglobin findings were similar (i.v.: 16.7%-57.1%; s.c.: 11.1%‒42.9%). Dose-related achievement of ≥2% increase in femoral neck cortical BMD was seen among only REN-001 patients receiving sotatercept (0.3‒0.7 mg/kg: 20.0%‒57.1%; placebo: 0.0%). Abdominal aortic vascular calcification was slowed in a dose-related manner, with a ≤15% increase in Agatston score achieved by more REN-001 sotatercept versus placebo patients (60%‒100% vs. 16.7%). The most common adverse events during treatment were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza observed in both treatment and placebo groups. Conclusion: In patients with ESKD, sotatercept exhibited a favorable safety profile and was associated with trends in dose-related slowing of vascular calcification. Less-consistent trends in improved hemoglobin concentration and BMD were observed

Using Multiple Unmanned Systems for a Site Security Task

Unmanned systems are often used to augment the ability of humans to perform challenging tasks. While the value of individual unmanned vehicles have been proven for a variety of tasks, it is less understood how multiple unmanned systems should be used together to accomplish larger missions such as site security. The purpose of this paper is to discuss efforts by researchers at the Idaho National Laboratory (INL) to explore the utility and practicality of operating multiple unmanned systems for a site security mission. This paper reviews the technology developed for a multi-agent mission and summarizes the lessons-learned from a technology demonstration

Save water or save wildlife? Water use and conservation in the central Sierran foothill oak woodlands of California, USA

More frequent drought is projected for California. As water supplies constrict, and urban growth and out-migration spread to rural areas, trade-offs in water use for agriculture, biodiversity conservation, fire hazard reduction, residential development, and quality of life will be exacerbated. The California Black Rail (Laterallus jamaicensis coturniculus), state listed as “Threatened,” depends on leaks from antiquated irrigation district irrigation systems for much of its remnant small wetland habitat in the north central Sierra Nevada foothills. Residents of the 1295 km² foothill habitat distribution of the Black Rail were surveyed about water use. Results show that the most Black Rail habitat is owned by those purchasing water to irrigate pasture, a use that commonly creates wetlands from leaks and tailwater. Promoting wildlife, agricultural production, and preventing wildfire are common resident goals that call for abundant and inexpensive water; social and economic pressures encourage reduction in water use and the repair of leaks that benefit wildlife and greenery. Broad inflexible state interventions to curtail water use are likely to create a multitude of unintended consequences, including loss of biodiversity and environmental quality, and alienation of residents as valued ecosystem services literally dry up. Adaptive and proactive policies are needed that consider the linkages in the social-ecological system, are sensitive to local conditions, prevent landscape dewatering, and recognize the beneficial use of water to support ecosystem services such as wildlife habitat. Much Black Rail habitat is anthropogenic, created at the nexus of local governance, plentiful water, agricultural practices, historical events, and changing land uses. This history should be recognized and leveraged rather than ignored in a rush to “save” water by unraveling the social-ecological system that created the landscape. Policy and governance needs to identify and prioritize habitat areas to maintain during drought.This project was funded as part of the NSF Coupled Human Natural Systems Program, Project Award Number 1115069, Wetlands in a Working Landscape, with Professor Steve Beissinger as Principal Investigator. J.L. Oviedo’s involvement in this study was also funded by the Salvador de Madariaga program (grant number PRX16/00452) of the Spanish Ministry of Education, Culture and Sports.Peer reviewe

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease