Temporal Analysis of the Honey Bee Microbiome Reveals Four Novel Viruses and Seasonal Prevalence of Known Viruses, Nosema, and Crithidia

Honey bees (Apis mellifera) play a critical role in global food production as pollinators of numerous crops. Recently, honey bee populations in the United States, Canada, and Europe have suffered an unexplained increase in annual losses due to a phenomenon known as Colony Collapse Disorder (CCD). Epidemiological analysis of CCD is confounded by a relative dearth of bee pathogen field studies. To identify what constitutes an abnormal pathophysiological condition in a honey bee colony, it is critical to have characterized the spectrum of exogenous infectious agents in healthy hives over time. We conducted a prospective study of a large scale migratory bee keeping operation using high-frequency sampling paired with comprehensive molecular detection methods, including a custom microarray, qPCR, and ultra deep sequencing. We established seasonal incidence and abundance of known viruses, Nosema sp., Crithidia mellificae, and bacteria. Ultra deep sequence analysis further identified four novel RNA viruses, two of which were the most abundant observed components of the honey bee microbiome (∼1011 viruses per honey bee). Our results demonstrate episodic viral incidence and distinct pathogen patterns between summer and winter time-points. Peak infection of common honey bee viruses and Nosema occurred in the summer, whereas levels of the trypanosomatid Crithidia mellificae and Lake Sinai virus 2, a novel virus, peaked in January

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Towards a realistic population of simulated galaxy groups and clusters

We present a new suite of large-volume cosmological hydrodynamical simulations called cosmo-OWLS. They form an extension to the OverWhelmingly Large Simulations (OWLS) project, and have been designed to help improve our understanding of cluster astrophysics and non-linear structure formation, which are now the limiting systematic errors when using clusters as cosmological probes. Starting from identical initial conditions in either the Planck or WMAP7 cosmologies, we systematically vary the most important ‘sub-grid’ physics, including feedback from supernovae and active galactic nuclei (AGN). We compare the properties of the simulated galaxy groups and clusters to a wide range of observational data, such as X-ray luminosity and temperature, gas mass fractions, entropy and density profiles, Sunyaev–Zel'dovich flux, I-band mass-to-light ratio, dominance of the brightest cluster galaxy and central massive black hole (BH) masses, by producing synthetic observations and mimicking observational analysis techniques. These comparisons demonstrate that some AGN feedback models can produce a realistic population of galaxy groups and clusters, broadly reproducing both the median trend and, for the first time, the scatter in physical properties over approximately two decades in mass (1013 M⊙ ≲ M500 ≲ 1015 M⊙) and 1.5 decades in radius (0.05 ≲ r/r500 ≲ 1.5). However, in other models, the AGN feedback is too violent (even though they reproduce the observed BH scaling relations), implying that calibration of the models is required. The production of realistic populations of simulated groups and clusters, as well as models that bracket the observations, opens the door to the creation of synthetic surveys for assisting the astrophysical and cosmological interpretation of cluster surveys, as well as quantifying the impact of selection effects

Evolution of species interactions determines microbial community productivity in new environments

Diversity generally increases ecosystem productivity over short timescales. Over longer timescales, both ecological and evolutionary responses to new environments could alter productivity and diversity–productivity relationships. In turn, diversity might affect how component species adapt to new conditions. We tested these ideas by culturing artificial microbial communities containing between 1 and 12 species in three different environments for ∼60 generations. The relationship between community yields and diversity became steeper over time in one environment. This occurred despite a general tendency for the separate yields of isolates of constituent species to be lower at the end if they had evolved in a more diverse community. Statistical comparisons of community and species yields showed that species interactions had evolved to be less negative over time, especially in more diverse communities. Diversity and evolution therefore interacted to enhance community productivity in a new environment

Physical and emotional development, appetite and body image in adolescents who failed to thrive as infants

Background: Previous studies suggest that failure to thrive in infancy may be associated with adverse sequelae in childhood. Although cognitive abilities have been extensively investigated, little systematic research is available on other aspects of development. Methods: Eighty-nine children who failed to thrive as infants and 91 controls were followed up when twelve years old and examined using anthropometric measurement, self-ratings of appetite and body image, the Dutch Eating Behaviour Questionnaire, the Self-perception Profile for Children, The Revised Children's Manifest Anxiety Scale, the parent and child form of the Mood and Feelings Questionnaire and the parent and teacher's form of the Child Behavior Checklist. Results: The children who failed to thrive were significantly shorter and lighter at twelve and had significantly lower BMIs, but they did not go into puberty any later. They were more likely to rate their appetite as lower than their best friend's, were generally more satisfied with their body shape, and had significantly lower restraint score on the Dutch Eating Behaviour Questionnaire. They were not significantly different from controls on any of the measures reflecting anxiety, depression or low self-esteem. Conclusions: Failure to thrive in infancy is not associated with adverse emotional development in childhood