Convergent input from brainstem coincidence detectors onto delay-sensitive neurons in the inferior colliculus.

Responses of low-frequency neurons in the inferior colliculus (IC) of anesthetized guinea pigs were studied with binaural beats to assess their mean best interaural phase (BP) to a range of stimulating frequencies. Phase plots (stimulating frequency vs BP) were produced, from which measures of characteristic delay (CD) and characteristic phase (CP) for each neuron were obtained. The CD provides an estimate of the difference in travel time from each ear to coincidence-detector neurons in the brainstem. The CP indicates the mechanism underpinning the coincidence detector responses. A linear phase plot indicates a single, constant delay between the coincidencedetector inputs from the two ears. In more than half (54 of 90) of the neurons, the phase plot was not linear. We hypothesized that neurons with nonlinear phase plots received convergent input from brainstem coincidence detectors with different CDs. Presentation of a second tone with a fixed, unfavorable delay suppressed the response of one input, linearizing the phase plot and revealing other inputs to be relatively simple coincidence detectors. For some neurons with highly complex phase plots, the suppressor tone altered BP values, but did not resolve the nature of the inputs. For neurons with linear phase plots, the suppressor tone either completely abolished their responses or reduced their discharge rate with no change in BP. By selectively suppressing inputs with a second tone, we are able to reveal the nature of underlying binaural inputs to IC neurons, confirming the hypothesis that the complex phase plots of many IC neurons are a result of convergence from simple brainstem coincidence detectors

Origin of basalts by hybridization in andesite-dominated arcs

Mafic magmas are common in subduction zone settings, yet their high density restricts their ascent to the surface. Once stalled in the crust, these magmas may differentiate, assimilate crust and other melts and mushes to produce hybridised intermediate magmas. The Soufriere Hills Volcano on Montserrat is a ‘type locality’ for these hybridisation processes and yet, just 3 km south of the crater, voluminous basalts have erupted from the South Soufriere Hills volcano within the same time period as the Soufriere Hills Volcano was erupting hybrid andesites (131 - 128 ka). Basaltic South Soufriere Hills magmas have 48 - 53 32 wt% SiO2 and 4 - 6 wt% MgO. They were hot (970 - 1160 °C), volatile-rich (melt inclusions contain up to 6.2 wt% H2O) and were stored at 8 – 13 km prior to eruption (based on olivine and pyroxene-hosted melt inclusion volatile geochemistry). Melt inclusions do not preserve basaltic liquids: they are andesitic to rhyolitic in composition, related to one another by a line of descent controlled by simple closed-system fractionation. Whole rock compositions, however, are best described by a hybridisation model involving “back”-mixing of andesitic to rhyolitic melts with mafic crystal phases such as magnetite, olivine, orthopyroxene and clinopyroxene. Phenocryst zoning illustrates repeated mixing events between evolved melts and mafic phenocrysts, which, when coupled with the heterogeneity of crystal compositions, strongly suggests that although the bulk composition is basalt (containing Fo80 olivine), they were assembled from disparate ingredients, likely derived from mafic crystal mushes and more evolved melt lenses of variable composition. The mixing events occur days to weeks prior to eruption. We propose that the South Soufriere Hills basaltic magmas, with their higher bulk density over andesites from neighbouring volcanoes, ultimately may have been eruptible owing to both the transtensional tectonics imposed by offshore grabens (related to the oblique subduction of the Lesser Antilles) and to surface unloading caused by large scale edifice collapse. Our observations support the idea that compositional changes in arcs might reflect not only changes in source compositions, but also effects caused by patterns in crustal strain and tectonics.MC and SFLW thank NERC for financial support via grant NE/K000403/1.This is the accepted manuscript. The final version is available from OUP at http://dx.doi.org/10.1093/petrology/egv00

The Role of Tephra in Enhancing Organic Carbon Preservation in Marine Sediments

Preservation of organic carbon (Corg) in marine sediments plays a major role in defining ocean-atmosphere CO2 levels, Earth climate, and the generation of hydrocarbons. Important controls over sedimentary Corg preservation include; biological productivity, Corg isolation from oxidants (mainly dissolved O2) in the overlying water column and sediments, and Corg – mineral association in sediments. Deposition of the products of explosive volcanism (tephra) in the oceans directly enhances Corg burial through all these mechanisms, and indirectly through enhanced formation of authigenic carbonate (Cauth) derived from sedimentary Corg. In the modern oceans, it is suggested that tephra deposition may account for 5–10% of the Corg burial flux and 10–40% of the Cauth burial flux. However, during certain periods in Earth's history, extensive explosive volcanism may have led to enhanced Cauth precipitation on a sufficiently large scale to influence the global ocean-atmosphere carbon cycle. Changes in tephra-related Corg preservation may also have played a role in increasing Corg preservation rates in local marine basins, at the oxic-anoxic boundary and enhanced the generation of hydrocarbon deposits in these settings

Strong but opposing effects of associational resistance and susceptibility on defense phenotype in an African savanna plant

The susceptibility of plants to herbivores can be strongly influenced by the identity, morphology and palatability of neighboring plants. While the defensive traits of neighbors often determine the mechanism and strength of associational resistance and susceptibility, the effect of neighbors on plant defense phenotype remains poorly understood. We used field surveys and a prickle-removal experiment in a semi-arid Kenyan savanna to evaluate the efficacy of physical defenses against large mammalian herbivores in a common understory plant, Solanum campylacanthum. We then quantified the respective effects of spinescent Acacia trees and short-statured grasses on browsing damage and prickle density in S. campylacanthum. We paired measurements of prickle density beneath and outside tree canopies with long-term herbivore-exclusion experiments to evaluate whether associational resistance reduced defense investment by decreasing browsing damage. Likewise, we compared defense phenotype within and outside pre-existing and experimentally created clearings to determine whether grass neighbors increased defense investment via associational susceptibility. Removing prickles increased the frequency of browsing by ~25%, and surveys of herbivory damage on defended leaves suggested that herbivores tended to avoid prickles. As predicted, associational resistance and susceptibility had opposing effects on plant phenotype: individuals growing beneath Acacia canopies (or, analogously, within large-herbivore exclosures) had a significantly lower proportion of their leaves browsed and produced ~ 70–80% fewer prickles than those outside refuges, whereas plants in grass-dominated clearings were more heavily browsed and produced nearly twice as many prickles as plants outside clearings. Our results demonstrate that associational resistance and susceptibility have strong, but opposing, effects on plant defense phenotype, and that variable herbivore damage is a major source of intraspecific variation in defense phenotype in this system

Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure

BACKGROUND Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. METHODS We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. RESULTS Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). CONCLUSIONS Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure

A Comparison of Three Methods of Mendelian Randomization when the Genetic Instrument, the Risk Factor and the Outcome Are All Binary

The method of instrumental variable (referred to as Mendelian randomization when the instrument is a genetic variant) has been initially developed to infer on a causal effect of a risk factor on some outcome of interest in a linear model. Adapting this method to nonlinear models, however, is known to be problematic. In this paper, we consider the simple case when the genetic instrument, the risk factor, and the outcome are all binary. We compare via simulations the usual two-stages estimate of a causal odds-ratio and its adjusted version with a recently proposed estimate in the context of a clinical trial with noncompliance. In contrast to the former two, we confirm that the latter is (under some conditions) a valid estimate of a causal odds-ratio defined in the subpopulation of compliers, and we propose its use in the context of Mendelian randomization. By analogy with a clinical trial with noncompliance, compliers are those individuals for whom the presence/absence of the risk factor X is determined by the presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z whatever the alleles randomly received at conception). We also recall and illustrate the huge variability of instrumental variable estimates when the instrument is weak (i.e., with a low percentage of compliers, as is typically the case with genetic instruments for which this proportion is frequently smaller than 10%) where the inter-quartile range of our simulated estimates was up to 18 times higher compared to a conventional (e.g., intention-to-treat) approach. We thus conclude that the need to find stronger instruments is probably as important as the need to develop a methodology allowing to consistently estimate a causal odds-ratio

Paediatric radiology seen from Africa. Part I: providing diagnostic imaging to a young population

Article approval pendingPaediatric radiology requires dedicated equipment, specific precautions related to ionising radiation, and specialist knowledge. Developing countries face difficulties in providing adequate imaging services for children. In many African countries, children represent an increasing proportion of the population, and additional challenges follow from extreme living conditions, poverty, lack of parental care, and exposure to tuberculosis, HIV, pneumonia, diarrhoea and violent trauma. Imaging plays a critical role in the treatment of these children, but is expensive and difficult to provide. The World Health Organisation initiatives, of which the World Health Imaging System for Radiography (WHIS-RAD) unit is one result, needs to expand into other areas such as the provision of maintenance servicing. New initiatives by groups such as Rotary and the World Health Imaging Alliance to install WHIS-RAD units in developing countries and provide digital solutions, need support. Paediatric radiologists are needed to offer their services for reporting, consultation and quality assurance for free by way of teleradiology. Societies for paediatric radiology are needed to focus on providing a volunteer teleradiology reporting group, information on child safety for basic imaging, guidelines for investigations specific to the disease spectrum, and solutions for optimising imaging in children

Chlorhexidine Substantivity on Salivary Flora and Plaque-Like Biofilm: An In Situ Model

This work was supported by project FIS PI11/01383 from Carlos III Institute of Health (Ministry of Economy and Competitiveness, Madrid, Spain

Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.

AIMS/HYPOTHESIS: There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. METHODS: We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK. RESULTS: We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p <or= 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99-1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09-1.21] per 0.28 SD increase in IL-18 levels). CONCLUSIONS/INTERPRETATION: Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk, including type 1 diabetes, alter type 2 diabetes risk

Group formation under limited resources: narrow basin of equality

The formation of groups in competition and the aggressive interactions between them are ubiquitous phenomena in society. These include student activities in the classroom, election races between political parties, and intensifying trade wars between countries. Why do individuals form themselves into groups? What is the optimal size of groups? And how does the group size distribution affect resource allocations? These questions have been the subjects of intense research in economics, political science, sociology, and ethology. In this study, we explore the group-size effects on the formation of groups and resource allocations from an economic standpoint. While being in a large group is generally advantageous in competition, an increase in the management costs would set an upper bound to the individual benefit of members. Under such counteracting size effects, we consider the dynamics of group formation in which people seek a conservative measure to reduce their possible maximum loss. We are especially interested in the effects of group size on social inequalities at both group and individual level in resource allocation. Our findings show that the low positive size-effect and the high negative size-effect result in different types of social inequalities. We conclude, from the relation between the inequality measures and group distributions predicted within the model, that overall social equality only can be achieved within a narrow region where two counteracting size-effects are balanced