Determinants of gain modulation enabled by short-term depression at an inhibitory cerebellar synapse

Abstract from the 23rd Annual Computational Neuroscience Meeting: CNS 2014. © 2014 Bampasakis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedNeurons adapt rapidly the slope, also known as gain, of their input-output function to time-varying conditions. Gain modulation is a prominent mechanism in many brain processes, such as auditory processing and attention scaling of orientation tuning curves.Peer reviewe

Spotting the diffusion of New Psychoactive Substances over the Internet

Online availability and diffusion of New Psychoactive Substances (NPS) represent an emerging threat to healthcare systems. In this work, we analyse drugs forums, online shops, and Twitter. By mining the data from these sources, it is possible to understand the dynamics of drugs diffusion and their endorsement, as well as timely detecting new substances. We propose a set of visual analytics tools to support analysts in tackling NPS spreading and provide a better insight about drugs market and analysis

Reduced or modified dietary fat for preventing cardiovascular disease

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Influence of Solvent Composition on the Crystal Morphology and Structure of p-Aminobenzoic Acid Crystallised from Mixed Ethanol and Nitromethane Solutions

The crystallization of α-p-aminobenzoic acid (pABA) from mixed solutions in ethanol (EtOH) and nitromethane (NMe) is reported. From solutions with compositions >60 wt % NMe, the known α-polymorph of pABA appears. In contrast, crystals prepared from mixed solvent with <60 wt % NMe reveal the presence of a previously unknown NMe solvate, which crystallizes concomitantly with the α-form. The crystal structure of this new form has been determined and is compared with the previously known structure of the α-polymorph. The crystal structure of the NMe solvate has similar synthonic interactions with respect to α-pABA, in particular, the OH···O H-bonded dimers and the NH···O H-bonds between the pABA molecules. However, the π–π stacking interactions between the phenyl ring groups are found to be much more offset and do not form a continuous chain through the structure, as found in α-pABA. The synthonic interactions in the NMe solvate structure are generally weaker than those found in α-pABA, and the lattice energy is calculated to be significantly lower, suggesting the solvate structure is metastable with respect to α-pABA. The impact of NMe on the morphology of α-pABA crystals, together with molecular modelling results suggest that this solvent is able to disrupt the π–π stacking interactions that dominate growth along the needle (b-axis) direction of α-pABA, and are intimately linked to the ultimate formation of the solvate

Mendelian randomization for studying the effects of perturbing drug targets [version 2; peer review: 3 approved, 1 approved with reservations]

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline

Imaging Oxygen Distribution in Marine Sediments. The Importance of Bioturbation and Sediment Heterogeneity

The influence of sediment oxygen heterogeneity, due to bioturbation, on diffusive oxygen flux was investigated. Laboratory experiments were carried out with 3 macrobenthic species presenting different bioturbation behaviour patterns:the polychaetes Nereis diversicolor and Nereis virens, both constructing ventilated galleries in the sediment column, and the gastropod Cyclope neritea, a burrowing species which does not build any structure. Oxygen two-dimensional distribution in sediments was quantified by means of the optical planar optode technique. Diffusive oxygen fluxes (mean and integrated) and a variability index were calculated on the captured oxygen images. All species increased sediment oxygen heterogeneity compared to the controls without animals. This was particularly noticeable with the polychaetes because of the construction of more or less complex burrows. Integrated diffusive oxygen flux increased with oxygen heterogeneity due to the production of interface available for solute exchanges between overlying water and sediments. This work shows that sediment heterogeneity is an important feature of the control of oxygen exchanges at the sediment–water interface

Understanding animal fears: a comparison of the cognitive vulnerability and harm-looming models

Background: The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods: 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results: Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion: This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fearJason M Armfiel

Activating Generalized Fuzzy Implications from Galois Connections

This paper deals with the relation between fuzzy implications and Galois connections, trying to raise the awareness that the fuzzy implications are indispensable to generalise Formal Concept Analysis. The concrete goal of the paper is to make evident that Galois connections, which are at the heart of some of the generalizations of Formal Concept Analysis, can be interpreted as fuzzy incidents. Thus knowledge processing, discovery, exploration and visualization as well as data mining are new research areas for fuzzy implications as they are areas where Formal Concept Analysis has a niche.F.J. Valverde-Albacete—was partially supported by EU FP7 project LiMoSINe, (contract 288024). C. Peláez-Moreno—was partially supported by the Spanish Government-CICYT project 2011-268007/TEC.Publicad

Land Use Regression Models for Ultrafine Particles in Six European Areas

Long-term ultrafine particle (UFP) exposure estimates at a fine spatial scale are needed for epidemiological studies. Land use regression (LUR) models were developed and evaluated for six European areas based on repeated 30 min monitoring following standardized protocols. In each area; Basel (Switzerland), Heraklion (Greece), Amsterdam, Maastricht, and Utrecht ("The Netherlands"), Norwich (United Kingdom), Sabadell (Spain), and Turin (Italy), 160-240 sites were monitored to develop LUR models by supervised stepwise selection of GIS predictors. For each area and all areas combined, 10 models were developed in stratified random selections of 90% of sites. UFP prediction robustness was evaluated with the intraclass correlation coefficient (ICC) at 31-50 external sites per area. Models from Basel and The Netherlands were validated against repeated 24 h outdoor measurements. Structure and model R2 of local models were similar within, but varied between areas (e.g., 38-43% Turin; 25-31% Sabadell). Robustness of predictions within areas was high (ICC 0.73-0.98). External validation R2 was 53% in Basel and 50% in The Netherlands. Combined area models were robust (ICC 0.93-1.00) and explained UFP variation almost equally well as local models. In conclusion, robust UFP LUR models could be developed on short-term monitoring, explaining around 50% of spatial variance in longer-term measurements