Effects of the Burrowing Brittlestar, Microphiopholis gracillima (Echinodermata: Ophiuroidea), on the Flux of Lithium, an Inert Tracer, Across the Sediment-Water Interface

Burrowing and ventilation activities of infaunal organisms have been shown to affect geochemical processes in sediments and at the sediment-water interface. Although burrowing brittlestars are dominant in many benthic environments, their role in these processes is poorly known. We tested the effect of the amphiurid brittlestar, Microphiopholis gracillima, on the flux of lithium ion from the sediment to the overlying water by using sediment cores with false bottoms for continuous flow of a Li+1-seawater solution. Brittlestars at densities of 300 and 600 individuals m-2 caused a twofold increase in the rate that Li was transported through the sediment. Density of brittlestars appeared to have no effect on the flux of Li+1 from the sediment, indicating a possible threshold beyond which density increases do not influence fluxes of solute from the sediment

UK-India Centre for Advanced Technology for Minimizing Indiscriminate Use of Antibiotics:"Exploring biology of antibiotic resistance and potential targets for early diagnosis and effective management of infectious diseases”

YesDuring January 15th – 17th, 2017 a group of scientists met, under the auspices of the UK-India Centre for Advanced Technology for Minimizing Indiscriminate Use of Antibiotics, to discuss the further developments and potential solutions to antimicrobial resistance. This was the third work shop under this funding stream held in Hyderabad. The presentations and outcomes of the workshop are released here. Key out comes included the need to address improved treatment and detection of TB, delivery of antimicrobial peptides, potential strategies for combating beta-lactam resistance.Medical Research Counci

Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies

BACKGROUND: Dietary inorganic nitrate (NO(3)(−)) is a polyatomic ion, which is present in large quantities in green leafy vegetables and beetroot, and has attracted considerable attention in recent years as a potential health-promoting dietary compound. Numerous small, well-controlled laboratory studies have reported beneficial health effects of inorganic NO(3)(−) consumption on blood pressure, endothelial function, cerebrovascular blood flow, cognitive function, and exercise performance. Translating the findings from small laboratory studies into ‘real-world’ applications requires careful consideration. MAIN BODY: This article provides a brief overview of the existing empirical evidence basis for the purported health-promoting effects of dietary NO(3)(−) consumption. Key areas for future research are then proposed to evaluate whether promising findings observed in small animal and human laboratory studies can effectively translate into clinically relevant improvements in population health. These proposals include: 1) conducting large-scale, longer duration trials with hard clinical endpoints (e.g. cardiovascular disease incidence); 2) exploring the feasibility and acceptability of different strategies to facilitate a prolonged increase in dietary NO(3)(−) intake; 3) exploitation of existing cohort studies to explore associations between NO(3)(−) intake and health outcomes, a research approach allowing larger samples sizes and longer duration follow up than is feasible in randomised controlled trials; 4) identifying factors which might account for individual differences in the response to inorganic NO(3)(−) (e.g. sex, genetics, habitual diet) and could assist with targeted/personalised nutritional interventions; 5) exploring the influence of oral health and medication on the therapeutic potential of NO(3)(−) supplementation; and 6) examining potential risk of adverse events with long term high- NO(3)(−) diets. CONCLUSION: The salutary effects of dietary NO(3)(−) are well established in small, well-controlled laboratory studies. Much less is known about the feasibility and efficacy of long-term dietary NO(3)(−) enrichment for promoting health, and the factors which might explain the variable responsiveness to dietary NO(3)(−) supplementation between individuals. Future research focussing on the translation of laboratory data will provide valuable insight into the potential applications of dietary NO(3)(−) supplementation to improve population health

Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials

Background: This study assessed the immunogenicity of pegvaliase (recombinant Anabaena variabilis phenylalanine [Phe] ammonia lyase [PAL] conjugated with polyethylene glycol [PEG]) treatment in adults with phenylketonuria (PKU) and its impact on safety and efficacy. Methods: Immunogenicity was assessed during induction, upward titration, and maintenance dosing regimens in adults with PKU (n = 261). Total antidrug antibodies (ADA), neutralizing antibodies, immunoglobulin (Ig) M and IgG antibodies against PAL and PEG, IgG and IgM circulating immune complex (CIC) levels, complement components 3 and 4 (C3/C4), plasma Phe, and safety were assessed at baseline and throughout the study. Pegvaliase-specific IgE levels were measured in patients after hypersensitivity adverse events (HAE). Findings: All patients developed ADA against PAL, peaking by 6 months and then stabilizing. Most developed transient antibody responses against PEG, peaking by 3 months, then returning to baseline by 9 months. Binding of ADA to pegvaliase led to CIC formation and complement activation, which were highest during early treatment. Blood Phe decreased over time as CIC levels and complement activation declined and pegvaliase dosage increased. HAEs were most frequent during early treatment and declined over time. No patient with acute systemic hypersensitivity events tested positive for pegvaliase-specific IgE near the time of the event. Laboratory evidence was consistent with immune complex-mediated type III hypersensitivity. No evidence of pegvaliase-associated IC-mediated end organ damage was noted. Interpretation: Despite a universal ADA response post-pegvaliase administration, adult patients with PKU achieved substantial and sustained blood Phe reductions with a manageable safety profile. Fund: BioMarin Pharmaceutical Inc. Keywords: Enzyme replacement therapy, Antidrug antibody, Circulating immune complex, Hypersensitivity, Phenylalanin

Effects of Greenhouse Gases Like Carbon Dioxide Can Be Spotted Earlier in the Middle Atmosphere

Understanding and dealing with climate change requires us to look at the atmosphere as a whole, not just the lowest portion near the surface. Analyzing the effects of greenhouse gases on the middle atmosphere helps to identify and understand the effects of climate change early on.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation

Purpose: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay. Methods: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n=85) within the first 72h of ICU stay with an expected ICU stay of ≥48h and sedation need for ≥24h after randomization. Patients were assigned to either DEX (≤1.4μgkg−1h−1; n=41) or SC (n=44), with daily sedation stops. Results: Non-inferiority of DEX versus SC was not confirmed. Target Richmond agitation-sedation score (RASS) was reached a median of 64% (DEX) and 63% (SC) of the sedation time (ns). The length of ICU stay was similar in DEX and SC. Patients with RASS target 0-3 (DEX 78%, SC 80%) were at target sedation 74% (DEX) and 64% (SC) of the time (ns), whereas those with RASS target −4 or less reached the target 42% (DEX) and 62% (SC) of the time (P=.006). Post hoc analyses suggested shorter duration of mechanical ventilation for DEX (P=0.025). Conclusions: This pilot study suggests that in long-term sedation, DEX is comparable to SC in maintaining sedation targets of RASS 0 to −3 but not suitable for deep sedation (RASS −4 or less). DEX had no effect on length of ICU stay. Its effects on other relevant clinical outcomes, such as duration of mechanical ventilation, should be tested furthe

An 11.5 W Yb:YAG planar waveguide laser fabricated via pulsed laser deposition

We present details of the homo-epitaxial growth of Yb:YAG onto a <100> oriented YAG substrate by pulsed laser deposition. Material characterization and initial laser experiments are also reported, including the demonstration of laser action from the 15 µm-thick planar waveguide generating 11.5 W of output power with a slope efficiency of 48%. This work indicates that under appropriate conditions, high-quality single-crystal Yb:YAG growth via pulsed laser deposition is achievable with characteristics comparable to those obtained via conventional crystal growth techniques