On the accuracy of PLIF measurements in slender plumes

The purpose of this article was to assess the measurement uncertainty of the planar laser-induced fluorescence (PLIF) method and, as much as possible, to devise corrections for predictable biases. More specifically, we considered the measurement of concentration maps in cross sections parallel to and normal to the axis of a slender plume containing Rhodamine 6G as a passive scalar tracer and transported by a turbulent shear flow. In addition to previously examined sources of error related to PLIF, we also investigated several unexplored ones. First, we demonstrated that errors would arise if the laser sheet thickness was comparable to or larger than the thickness of the instantaneous plume. We then investigated the effect of secondary fluorescence, which was attributed to absorption and re-emission of primary fluorescence by dye both within and outside the laser sheet. We found that, if uncorrected, this effect would contaminate the calibration as well as the instantaneous concentration measurements of the plume, and proposed methods for the correction of these errors and for identifying the instantaneous boundaries of the in-sheet dye regions

Ocean acidification reduces demersal zooplankton that reside in tropical coral reefs

The in situ effects of ocean acidification on zooplankton communities remain largely unexplored. Using natural volcanic CO2 seep sites around tropical coral communities, we show a threefold reduction in the biomass of demersal zooplankton in high-CO2 sites compared with sites with ambient CO2. Differences were consistent across two reefs and three expeditions. Abundances were reduced in most taxonomic groups. There were no regime shifts in zooplankton community composition and no differences in fatty acid composition between CO2 levels, suggesting that ocean acidification affects the food quantity but not the quality for nocturnal plankton feeders. Emergence trap data show that the observed reduction in demersal plankton may be partly attributable to altered habitat. Ocean acidification changes coral community composition from branching to massive bouldering coral species, and our data suggest that bouldering corals represent inferior daytime shelter for demersal zooplankton. Since zooplankton represent a major source of nutrients for corals, fish and other planktivores, this ecological feedback may represent an additional mechanism of how coral reefs will be affected by ocean acidification

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

Characterising and Predicting Benthic Biodiversity for Conservation Planning in Deepwater Environments

Understanding patterns of biodiversity in deep sea systems is increasingly important because human activities are extending further into these areas. However, obtaining data is difficult, limiting the ability of science to inform management decisions. We have used three different methods of quantifying biodiversity to describe patterns of biodiversity in an area that includes two marine reserves in deep water off southern Australia. We used biological data collected during a recent survey, combined with extensive physical data to model, predict and map three different attributes of biodiversity: distributions of common species, beta diversity and rank abundance distributions (RAD). The distribution of each of eight common species was unique, although all the species respond to a depth-correlated physical gradient. Changes in composition (beta diversity) were large, even between sites with very similar environmental conditions. Composition at any one site was highly uncertain, and the suite of species changed dramatically both across and down slope. In contrast, the distributions of the RAD components of biodiversity (community abundance, richness, and evenness) were relatively smooth across the study area, suggesting that assemblage structure (i.e. the distribution of abundances of species) is limited, irrespective of species composition. Seamounts had similar biodiversity based on metrics of species presence, beta diversity, total abundance, richness and evenness to the adjacent continental slope in the same depth ranges. These analyses suggest that conservation objectives need to clearly identify which aspects of biodiversity are valued, and employ an appropriate suite of methods to address these aspects, to ensure that conservation goals are met

Seven newly identified loci for autoimmune thyroid disease

Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases

Effects of acute tryptophan depletion on executive function in healthy male volunteers

BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions

In Vivo Methods to Study Uptake of Nanoparticles into the Brain

Several in vivo techniques have been developed to study and measure the uptake of CNS compounds into the brain. With these techniques, various parameters can be determined after drug administration, including the blood-to-brain influx constant (Kin), the permeability-surface area (PS) product, and the brain uptake index (BUI). These techniques have been mostly used for drugs that are expected to enter the brain via transmembrane diffusion or by carrier-mediated transcytosis. Drugs that have limitations in entering the brain via such pathways have been encapsulated in nanoparticles (based on lipids or synthetic polymers) to enhance brain uptake. Nanoparticles are different from CNS compounds in size, composition and uptake mechanisms. This has led to different methods and approaches to study brain uptake in vivo. Here we discuss the techniques generally used to measure nanoparticle uptake in addition to the techniques used for CNS compounds. Techniques include visualization methods, behavioral tests, and quantitative methods

Periodic actin structures in neuronal axons are required to maintain microtubules

Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organisation and function, combining versatile Drosophila genetics with super-resolution microscopy and various functional readouts. Analyses with 11 different actin regulators and 3 actin-targeting drugs suggest PMS to contain short actin filaments which are depolymerisation resistant and sensitive to spectrin, adducin and nucleator deficiency - consistent with microscopy-derived models proposing PMS as specialised cortical actin. Upon actin removal we observed gaps in microtubule bundles, reduced microtubule polymerisation and reduced axon numbers suggesting a role of PMS in microtubule organisation. These effects become strongly enhanced when carried out in neurons lacking the microtubule-stabilising protein Short stop (Shot). Combining the aforementioned actin manipulations with Shot deficiency revealed a close correlation between PMS abundance and microtubule regulation, consistent with a model in which PMS-dependent microtubule polymerisation contributes to their maintenance in axons. We discuss potential implications of this novel PMS function along axon shafts for axon maintenance and regeneration