What Drives Reproductive Maturity and Efficiency in Serotinous Boreal Conifers?

In boreal North America, much of the landscape is covered by fire-adapted forests dominated by serotinous conifers. For these forests, reductions in fire return interval could limit reproductive success, owing to insufficient time for stands to reach reproductive maturity i.e., to initiate cone production. Improved understanding of the drivers of reproductive maturity can provide important information about the capacity of these forests to self-replace following fire. Here, we assessed the drivers of reproductive maturity in two dominant and widespread conifers, semi-serotinous black spruce and serotinous jack pine. Presence or absence of female cones were recorded in approximately 15,000 individuals within old and recently burned stands in two distinct ecozones of the Northwest Territories (NWT), Canada. Our results show that reproductive maturity was triggered by a minimum tree size threshold rather than an age threshold, with trees reaching reproductive maturity at smaller sizes where environmental conditions were more stressful. The number of reproductive trees per plot increased with stem density, basal area, and at higher latitudes (colder locations). The harsh climatic conditions present at these higher latitudes, however, limited the recruitment of jack pine at the treeline ecotone. The number of reproductive black spruce trees increased with deeper soils, whereas the number of reproductive jack pine trees increased where soils were shallower. We examined the reproductive efficiency i.e., the number of seedlings recruited per reproductive tree, linking pre-fire reproductive maturity of recently burned stands and post-fire seedling recruitment (recorded up to 4 years after the fires) and found that a reproductive jack pine can recruit on average three times more seedlings than a reproductive black spruce. We suggest that the higher reproductive efficiency of jack pine can explain the greater resilience of this species to wildfire compared with black spruce. Overall, these results help link life history characteristics, such as reproductive maturity, to variation in post-fire recruitment of dominant serotinous conifers

Community engagement and population coverage in mass anti-malarial administrations: a systematic literature review

BACKGROUND: Mass anti-malarial administration has been proposed as a key component of the malaria elimination strategy in South East Asia. The success of this approach depends on the local malaria epidemiology, nature of the anti-malarial regimen and population coverage. Community engagement is used to promote population coverage but little research has systematically analysed its impact. This systematic review examines population coverage and community engagement in programmes of mass anti-malarial drug administration. METHODS: This review builds on a previous review that identified 3049 articles describing mass anti-malarial administrations published between 1913 and 2011. Further search and application of a set of criteria conducted in the current review resulted in 51 articles that were retained for analysis. These 51 papers described the population coverage and/or community engagement in mass anti-malarial administrations. Population coverage was quantitatively assessed and a thematic analysis was conducted on the community engagement activities. RESULTS: The studies were conducted in 26 countries: in diverse healthcare and social contexts where various anti-malarial regimens under varied study designs were administered. Twenty-eight articles reported only population coverage; 12 described only community engagement activities; and 11 community engagement and population coverage. Average population coverage was 83% but methods of calculating coverage were frequently unclear or inconsistent. Community engagement activities included providing health education and incentives, using community structures (e.g. existing hierarchies or health infrastructure), mobilizing human resources, and collaborating with government at some level (e.g. ministries of health). Community engagement was often a process involving various activities throughout the duration of the intervention. CONCLUSION: The mean population coverage was over 80% but incomplete reporting of calculation methods limits conclusions and comparisons between studies. Various community engagement activities and approaches were described, but many articles contained limited or no details. Other factors relevant to population coverage, such as the social, cultural and study context were scarcely reported. Further research is needed to understand the factors that influence population coverage and adherence in mass anti-malarial administrations and the role community engagement activities and approaches play in satisfactory participation

Patterns of Ecosystem Structure and Wildfire Carbon Combustion Across Six Ecoregions of the North American Boreal Forest

Increases in fire frequency, extent, and severity are expected to strongly impact the structure and function of boreal forest ecosystems. An important function of the boreal forest is its ability to sequester and store carbon (C). Increasing disturbance from wildfires, emitting large amounts of C to the atmosphere, may create a positive feedback to climate warming. Variation in ecosystem structure and function throughout the boreal forest is important for predicting the effects of climate warming and changing fire regimes on C dynamics. In this study, we compiled data on soil characteristics, stand structure, pre-fire C pools, C loss from fire, and the potential drivers of these C metrics from 527 sites distributed across six ecoregions of North America’s western boreal forests. We assessed structural and functional differences between these fire-prone ecoregions using data from 417 recently burned sites (2004–2015) and estimated ecoregion-specific relationships between soil characteristics and depth from 167 of these sites plus an additional 110 sites (27 burned, 83 unburned). We found that northern boreal ecoregions were generally older, stored and emitted proportionally more belowground than aboveground C, and exhibited lower rates of C accumulation over time than southern ecoregions. We present ecoregion-specific estimates of depth-wise soil characteristics that are important for predicting C combustion from fire. As climate continues to warm and disturbance from wildfires increases, the C dynamics of these fire-prone ecoregions are likely to change with significant implications for the global C cycle and its feedbacks to climate change

GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health.

Funder: Department of HealthMosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04-11.81], p = 1.3 × 10-10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51-10.61], p = 1.8 × 10-12), 4 kg higher fat mass (p = 1.3 × 10-4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10-4) and 4.5 kg lower handgrip strength (p = 4.7 × 10-7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD:results on cardiovascular safety from the IMPACT trial

BACKGROUND: This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. METHODS: IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. RESULTS: Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. CONCLUSIONS: In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10-11% and 1-3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. TRIAL REGISTRATION: NCT02164513 (GSK study number CTT116855)

Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.

The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor whose disruption causes obesity. We functionally characterized 61 MC4R variants identified in 0.5 million people from UK Biobank and examined their associations with body mass index (BMI) and obesity-related cardiometabolic diseases. We found that the maximal efficacy of β-arrestin recruitment to MC4R, rather than canonical Gαs-mediated cyclic adenosine-monophosphate production, explained 88% of the variance in the association of MC4R variants with BMI. While most MC4R variants caused loss of function, a subset caused gain of function; these variants were associated with significantly lower BMI and lower odds of obesity, type 2 diabetes, and coronary artery disease. Protective associations were driven by MC4R variants exhibiting signaling bias toward β-arrestin recruitment and increased mitogen-activated protein kinase pathway activation. Harnessing β-arrestin-biased MC4R signaling may represent an effective strategy for weight loss and the treatment of obesity-related cardiometabolic diseases

Extended-spectrum β-lactamase-producing Escherichia coli in human-derived and foodchain-derived samples from England, Wales, and Scotland: an epidemiological surveillance and typing study

Background: Escherichia coli isolates producing extended-spectrum βlactamases (‘ESBL-E. coli’) cause >5000 bacteraemias annually in the UK. The contribution of the food chain to this challenge is debated. Methods: Selective media were used to seek ESBL-E. coli in routinely-submitted human faeces, sewage, farm slurry, and retail foodstuffs in London, East Anglia, Northwest England, Scotland and Wales. Recovered isolates were sequenced and compared with 293 bloodstream and 83 veterinary surveillance ESBL-E. coli isolates from the same regions. Findings: 10.7% (2157/20243) of human faeces contained ESBL-E. coli, rising to 17.0% (678/3995) in London. ESBL-E. coli also were frequent in sewage and present in 65.4% (104/159) of retail chicken, but rare in other meats and absent from plant-based foods. Sequence Type (ST) 131 dominated among ESBL-E. coli from human blood (188/293, 64.2%), faeces (128/360, 35.6%) and sewage (14/65, 21.5%) with STs 38 and 648 also widespread; CTX-M-15 was the predominant ESBL in these lineages. By contrast, STs 602, 23, 117 - mostly with CTX-M-1 ESBL - dominated among food and veterinary isolates, with only two ST131 organisms recovered. ST10 occurred in both animals and humans: being frequent in surveillance bovines and representing 4.2% (15/360) of human faecal isolates (but only 1% [3/293] from bacteraemias); however both human and animal ST10 isolates were diverse in serotype. Interpretation: Most human bacteraemias with ESBL-E. coli in the UK involve successful human-associated STs, particularly ST131; non-human reservoirs made little contribution to invasive human disease. Funding: NIHR Policy Research

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179