The global proportion and volume of unrecorded alcohol in 2015.

Alcohol consumption is associated with elevated risks of disease and injury, and the best indicator of the level of consumption in a country is total alcohol per capita (APC) consumption among adults which comprises recorded consumption and unrecorded consumption. While recorded consumption can be assessed with small measurement bias via taxation or other governmental records, unrecorded consumption is more difficult to assess. The objectives of this study were to estimate the country-specific proportion and volume of unrecorded APC in 2015, to identify main sources of unrecorded alcohol and to assess to what extent experts perceive unrecorded alcohol as a public health, social, and financial problem. Estimates of unrecorded APC were based on a multilevel fractional response regression model using data from World Health Organization's (WHO) STEPwise approach to surveillance surveys (16 countries, 66 188 participants), estimates from the routine WHO reporting on key indicators of alcohol use (189 countries), and a nominal group expert assessment (42 countries, 129 experts). Expert assessments also included data on the sources of unrecorded alcohol and the perception of unrecorded alcohol as a public health, social, and financial problem. The volume of global unrecorded APC was 1.6 L pure alcohol, representing 25% of the total APC. The volume of unrecorded APC was highest in Europe (2.1 L per capita), while the proportion of unrecorded APC was highest in the WHO Eastern Mediterranean region (57% of the total alcohol). In countries with available data, homemade alcohol was identified as a major source of unrecorded alcohol. The majority of experts considered unrecorded alcohol to be a public health (62%), social (60%), and financial problem (54%). High volumes of unrecorded alcohol are consumed globally; however, the volumes consumed and the sources of the unrecorded alcohol exhibit large geographical variation

Detecting ground level enhancements using soil moisture sensor networks

Ground level enhancements (GLEs) are space weather events that pose a potential hazard to the aviation environment through single event effects in avionics and increased dose to passengers and crew. The existing ground level neutron monitoring network provides continuous and well-characterized measurements of the radiation environment. However, there are only a few dozen active stations worldwide, and there has not been a UK-based station for several decades. Much smaller neutron detectors are increasingly deployed throughout the world with the purpose of using secondary neutrons from cosmic rays to monitor local soil moisture conditions (COSMOS). Space weather signals from GLEs and Forbush decreases have been identified in COSMOS data. Monte Carlo simulations of atmospheric radiation propagation show that a single COSMOS detector is sufficient to detect the signal of a medium-strength (10%–100% increase above background) GLE at high statistical significance, including at fine temporal resolution. Use of fine temporal resolution would also provide a capability to detect Terrestrial Gamma Ray Flashes (via secondary neutrons) which are produced by certain lightning discharges and which can provide a hazard to aircraft, particularly in tropical regions. We also show how the COsmic-ray Soil Moisture Observing System-UK detector network could be used to provide warnings at the International Civil Aviation Organization “Moderate” and “Severe” dose rate thresholds at aviation altitudes, and how multiple-detector hubs situated at strategic UK locations could detect a small GLE at high statistical significance and infer crucial information on the nature of the primary spectrum

The toxicity of angiotensin converting enzyme inhibitors to larvae of the disease vectors Aedes aegypti and Anopheles gambiae

The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3rd instars showing greater resistance. Mortality was also high within 24 h of exposure of 1st, 2nd and 3rd instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1st instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides

Biogeochemical and climate drivers of wetland phosphorus and nitrogen release: implications for nutrient legacies and eutrophication risk

The dynamics and processes of nutrient cycling and release were examined for a lowland wetland‐pond system, draining woodland in southern England. Hydrochemical and meteorological data were analyzed from 1997 to 2017, along with high‐resolution in situ sensor measurements from 2016 to 2017. The results showed that even a relatively pristine wetland can become a source of highly bioavailable phosphorus (P), nitrogen (N), and silicon (Si) during low‐flow periods of high ecological sensitivity. The drivers of nutrient release were primary production and accumulation of biomass, which provided a carbon (C) source for microbial respiration and, via mineralization, a source of bioavailable nutrients for P and N co‐limited microorganisms. During high‐intensity nutrient release events, the dominant N‐cycling process switched from denitrification to nitrate ammonification, and a positive feedback cycle of P and N release was sustained over several months during summer and fall. Temperature controls on microbial activity were the primary drivers of short‐term (day‐to‐day) variability in P release, with subdaily (diurnal) fluctuations in P concentrations driven by water body metabolism. Interannual relationships between nutrient release and climate variables indicated “memory” effects of antecedent climate drivers through accumulated legacy organic matter from the previous year's biomass production. Natural flood management initiatives promote the use of wetlands as “nature‐based solutions” in climate change adaptation, flood management, and soil and water conservation. This study highlights potential water quality trade‐offs and shows how the convergence of climate and biogeochemical drivers of wetland nutrient release can amplify background nutrient signals by mobilizing legacy nutrients, causing water quality impairment and accelerating eutrophication risk

First Transcriptome of the Testis-Vas Deferens-Male Accessory Gland and Proteome of the Spermatophore from Dermacentor variabilis (Acari: Ixodidae)

Ticks are important vectors of numerous human diseases and animal diseases. Feeding stimulates spermatogenesis, mating and insemination of male factors that trigger female reproduction. The physiology of male reproduction and its regulation of female development are essentially a black box. Several transcriptomes have catalogued expression of tick genes in the salivary glands, synganglion and midgut but no comprehensive investigation has addressed male reproduction and mating. Consequently, a new global approach using transcriptomics, proteomics, and quantitative gene expression is needed to understand male reproduction and stimulation of female reproduction

Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children

<p>Abstract</p> <p>Background</p> <p>Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (<it>BDNF</it>), the serotonin transporter (<it>SLC6A4</it>), and catechol-O-methyltransferase (<it>COMT</it>).</p> <p>Methods</p> <p>Bipolar-I affected offspring triads (N = 173) were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital.</p> <p>Results</p> <p>We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36), the COMT-l allele (OR = 1.27, p = 0.1), or the HTTLPR short allele (OR = 0.87, p = 0.38).</p> <p>Conclusion</p> <p>Our study suggests that the markers examined thus far in <it>COMT </it>and <it>SLC6A4 </it>are not associated with pediatric bipolar disorder and that if the val66met marker in <it>BDNF </it>is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported.</p

The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease