Revealing the neural time-course of direct gaze processing via spatial frequency manipulation of faces

Direct gaze is a powerful social cue signalling the attention of another person toward oneself. Here we investigated the relevance of low spatial frequency (LSF) and high spatial frequency (HSF) in facial cues for direct gaze processing. We identified two distinct peaks in the ERP response, the N170 and N240 components. These two components were related to different stimulus conditions and influenced by different spatial frequencies. In particular, larger N170 and N240 amplitudes were observed for direct gaze than for averted gaze, but only in the N240 component was this effect modulated by spatial frequency, where it was reliant in LSF information. By contrast, larger N170 and N240 components were observed for faces than for non-facial stimuli, but this effect was only modulated by spatial frequency in the N170 component, where it relied on HSF information. The present study highlights the existence of two functionally distinct components related to direct gaze processing

Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome

An improved bias correction scheme based on comparative precipitation characteristics

Bias correction is a necessary post-processing procedure in order to use regional climate model (RCM) simulated local climate variables as the input data for hydrological models owing to systematic errors of RCMs. Most of present bias correction methods adjust statistical properties between observed and simulated data on the basis of calendar periods, e.g. month or season. However, this matching statistic is only a necessary condition, not a sufficient condition, as temporal distribution of the precipitation between observed and simulated data is ignored. This study suggests an improved bias correction scheme that considers not only statistical properties but also the temporal distribution between the time series of observed and modelled data. The ratio of the observed precipitation to simulated precipitation is used to compare the behaviour between the observed and modelled precipitation data, and three criteria are proposed when dividing bias correction periods: (1) underestimation of precipitation, (2) stability of /underestimation of precipitation, (2) stability of precipitation ratio and (3) oscillation of precipitation ratio. The results show that the output of the proposed bias correction method follows the trend of the observed precipitation better than that of the conventional bias correction method. This study indicates that temporal distribution should not be ignored when choosing a comparison period for bias correction. However, the study is only a preliminary attempt to address this important issue, and we hope it will stimulate more research activities to improve the methodology. Future efforts on several unsolved problems have been suggested such as how to find out the optimal group number to avoid the overfitting and underfitting conditions

Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF/MEK inhibitors in patients with BRAF mutant metastatic melanoma

Background: Patients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF/MEK inhibitors (BRAF/MEKi). Methods: Patients with V600BRAF mutant metastatic melanoma treated with BRAF/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group. Results: Of 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF/MEKi and PD1±IPI (16 vs 4 days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 (62% vs 44%), AJCC M1C/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1±IPI (34% vs 57%). Median follow-up from PD1±IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1 vs PD1 across most subgroups except for females, those with 3 years OS (area under the curve, AUC=0.74), while ECOG PS ≥1, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67). Conclusions: IPI+PD1 and PD1 after BRAF/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy. Keywords: immunotherapy; melanoma

Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats

In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high-intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a ‘dominant’ role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems

Mutation Rate Distribution Inferred from Coincident SNPs and Coincident Substitutions

Mutation rate variation has the potential to bias evolutionary inference, particularly when rates become much higher than the mean. We first confirm prior work that inferred the existence of cryptic, site-specific rate variation on the basis of coincident polymorphisms—sites that are segregating in both humans and chimpanzees. Then we extend this observation to a longer evolutionary timescale by identifying sites of coincident substitutions using four species. From these data, we develop analytic theory to infer the variance and skewness of the distribution of mutation rates. Even excluding CpG dinucleotides, we find a relatively large coefficient of variation and positive skew, which suggests that, although most sites in the genome have mutation rates near the mean, the distribution contains a long right-hand tail with a small number of sites having high mutation rates. At least for primates, these quickly mutating sites are few enough that the infinite sites model in population genetics remains appropriate

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed individuals in Buenos Aires, Argentina

Objective: Our objective was to estimate primary resistance in an urban setting in a developing country characterized by high antiretroviral (ARV) coverage over the diagnosed population and also by an important proportion of undiagnosed individuals, in order to determine whether any change in primary resistance occurred in the past five years. Design: We carried out a multi-site resistance surveillance study according to WHO HIV resistance guidelines, using a weighted sampling technique based on annual HIV case reports per site. Methods: Blood samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed between March 2010 and August 2011 at 20 HIV voluntary counselling and testing centres in Buenos Aires. Clinical records of enrolled patients at the time of diagnosis were compiled. Viral load and CD4 counts were performed on all samples. The pol gene was sequenced and the resistance profile determined. Phylogenetic analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis. Results: We found that 12 (7.9%) of the 152 successfully sequenced samples harboured primary resistance mutations, of which K103N and G190A were the most prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance mutations were largely the most prevalent (5.9%), accounting for 75% of all primary resistance and exhibiting a significant increase (p =0.0072) in prevalence during the past 10 years as compared to our previous study performed in 1997-2000 and in 2003-2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor primary resistance were low and similar to the one previously reported. Conclusions: Levels of primary NNRTI resistance in Buenos Aires appear to be increasing in the context of a sustained ARV coverage and a high proportion of undiagnosed HIV-positive individuals. © 2013 Rodriguez-Rodrigues N et al; licensee International AIDS Society.Fil: Rodriguez Rodrigues, Nahuel Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Duran, Adriana. Ministerio de Salud de la Nación; ArgentinaFil: Bouzas, Maria Belen. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas F. J. Muñiz; ArgentinaFil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas F. J. Muñiz; ArgentinaFil: Vila, Marcelo. Organizacion Mundial de la Salud; ArgentinaFil: Indyk, Debbie. Icahn School of Medicine at Mount Sinai; Estados UnidosFil: Bissio, Emiliano. Ministerio de Salud de la Nación; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Dilernia, Dario Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

The Self-Assessment Scale of Cognitive Complaints in Schizophrenia: A validation study in Tunisian population

<p>Abstract</p> <p>Background</p> <p>Despite a huge well-documented literature on cognitive deficits in schizophrenia, little is known about the own perception of patients regarding their cognitive functioning. The purpose of our study was to create a scale to collect subjective cognitive complaints of patients suffering from schizophrenia with Tunisian Arabic dialect as mother tongue and to proceed to a validation study of this scale.</p> <p>Methods</p> <p>The authors constructed the Self-Assessment Scale of Cognitive Complaints in Schizophrenia (SASCCS) based on a questionnaire covering five cognitive domains which are the most frequently reported in the literature to be impaired in schizophrenia. The scale consisted of 21 likert-type questions dealing with memory, attention, executive functions, language and praxia. In a second time, the authors proceeded to the study of psychometric qualities of the scale among 105 patients suffering from schizophrenia spectrum disorders (based on DSM- IV criteria). Patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment Functioning Scale (GAF scale) and the Calgary Depression Scale (CDS).</p> <p>Results</p> <p>The scale's reliability was proven to be good through Cronbach alpha coefficient equal to 0.85 and showing its good internal consistency. The intra-class correlation coefficient at 11 weeks was equal to 0.77 suggesting a good stability over time. Principal component analysis with Oblimin rotation was performed and yielded to six factors accounting for 58.28% of the total variance of the scale.</p> <p>Conclusion</p> <p>Given the good psychometric properties that have been revealed in this study, the SASCCS seems to be reliable to measure schizophrenic patients' perception of their own cognitive impairment. This kind of evaluation can't substitute for objective measures of cognitive performances in schizophrenia. The purpose of such an evaluation is to permit to the patient to express his own well-being and satisfaction of quality of life.</p

On-farm practices for the safe use of wastewater in urban and peri-urban horticulture

The drafting of this handbook was initiated in October 2007, in Ghana, by Ines Beernaerts, in the framework of the FAOKNUST project on “Evaluation of non-treatment options for maximizing public health benefits of WHO guidelines governing the use of wastewater in urban vegetable production in Ghana”. The Farmer Field School (FFS) approach was introduced in the FAO-KNUST project and materialized in this handbook to enhance the experimental learning of the (peri-) urban farmers. The best practices described in this handbook were designed and field-tested in a project funded by the CGIAR Challenge Program on Water and Food (CPWF) under the coordination of the Kwame Nkrumah University of Science and Technology (KNUST) and the International Water Management Institute (IWMI). This initiative was taken to enable the project to go beyond research and ensure the sustainability of the results