The missing N1 or jittered P2: Electrophysiological correlates of pattern glare in the time and frequency domain

Excessive sensitivity to certain visual stimuli (cortical hyperexcitability) is associated with a number of neurological disorders including migraine, epilepsy, multiple sclerosis, autism and possibly dyslexia. Others show disruptive sensitivity to visual stimuli with no other obvious pathology or symptom profile (visual stress) which can extend to discomfort and nausea. We used event-related potentials (ERPs) to explore the neural correlates of visual stress and headache proneness. We analysed ERPs in response to thick (0.37 cycles per degree [c/deg]), medium (3 c/deg) and thin (12 c/deg) gratings, using mass univariate analysis, considering three factors in the general population: headache proneness, visual stress and discomfort. We found relationships between ERP features and the headache and discomfort factors. Stimulus main effects were driven by the medium stimulus regardless of participant characteristics. Participants with high discomfort ratings had larger P1 components for the initial presentation of medium stimuli, suggesting initial cortical hyperexcitability that is later suppressed. The participants with high headache ratings showed atypical N1-P2 components for medium stripes relative to the other stimuli. This effect was present only after repeated stimulus presentation. These effects were also explored in the frequency domain, suggesting variations in intertrial theta band phase coherence. Our results suggest that discomfort and headache in response to striped stimuli are related to different neural processes; however, more exploration is needed to determine whether the results translate to a clinical migraine population

Investigating the association of rs2910164 with cancer predisposition in an Irish cohort.

IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that exert post-transcriptional effects on gene expression by binding with cis-regulatory regions in target messenger RNA (mRNA). Polymorphisms in genes encoding miRNAs or in miRNA-mRNA binding sites confer deleterious epigenetic effects on cancer risk. miR-146a has a role in inflammation and may have a role as a tumour suppressor. The polymorphism rs2910164 in the MIR146A gene encoding pre-miR-146a has been implicated in several inflammatory pathologies, including cancers of the breast and thyroid, although evidence for the associations has been conflicting in different populations. We aimed to further investigate the association of this variant with these two cancers in an Irish cohort.MethodsThe study group comprised patients with breast cancer (BC), patients with differentiated thyroid cancer (DTC) and unaffected controls. Germline DNA was extracted from blood or from saliva collected using the DNA Genotek Oragene 575 collection kit, using crystallisation precipitation, and genotyped using TaqMan-based PCR. Data were analysed using SPSS, v22.ResultsThe total study group included 1516 participants. This comprised 1386 Irish participants; 724 unaffected individuals (controls), 523 patients with breast cancer (BC), 136 patients with differentiated thyroid cancer (DTC) and three patients with dual primary breast and thyroid cancer. An additional cohort of 130 patients with DTC from the South of France was also genotyped for the variant. The variant was detected with a minor allele frequency (MAF) of 0.19 in controls, 0.22 in BC and 0.27 and 0.26 in DTC cases from Ireland and France, respectively. The variant was not significantly associated with BC (per allele odds ratio = 1.20 (0.98-1.46), P  = 0.07), but was associated with DTC in Irish patients (per allele OR = 1.59 (1.18-2.14), P = 0.002).ConclusionThe rs2910164 variant in MIR146A is significantly associated with DTC, but is not significantly associated with BC in this cohort

A controlled trial of natalizumab for relapsing multiple sclerosis.

Background: In patients with multiple sclerosis, inflammatory brain lesions appear to arise from autoimmune responses involving activated lymphocytes and monocytes. The glycoprotein (alpha)(sub 4) integrin is expressed on the surface of these cells and plays a critical part in their adhesion to the vascular endothelium and migration into the parenchyma. Natalizumab is an (alpha)(sub 4) integrin antagonist that reduced the development of brain lesions in experimental models and in a preliminary study of patients with multiple sclerosis.Methods: In a randomized, double-blind trial, we randomly assigned a total of 213 patients with relapsing-remitting or relapsing secondary progressive multiple sclerosis to receive 3 mg of intravenous natalizumab per kilogram of body weight (68 patients), 6 mg per kilogram (74 patients), or placebo (71 patients) every 28 days for 6 months. The primary end point was the number of new brain lesions on monthly gadolinium-enhanced magnetic resonance imaging during the six-month treatment period. Clinical outcomes included relapses and self-reported well-being.Results: There were marked reductions in the mean number of new lesions in both natalizumab groups: 9.6 per patient in the placebo group, as compared with 0.7 in the group given 3 mg of natalizumab per kilogram (P<0.001) and 1.1 in the group given 6 mg of natalizumab per kilogram (P<0.001). Twenty-seven patients in the placebo group had relapses, as compared with 13 in the group given 3 mg of natalizumab per kilogram (P=0.02) and 14 in the group given 6 mg of natalizumab per kilogram (P=0.02). The placebo group reported a slight worsening in well-being (a mean decrease of 1.38 mm on a 100-mm visual-analogue scale), whereas the natalizumab groups reported an improvement (mean increase of 9.49 mm in the group given 3 mg of natalizumab per kilogram and 6.21 mm in the group given 6 mg of natalizumab per kilogram).Conclusions: In a placebo-controlled trial, treatment with natalizumab led to fewer inflammatory brain lesions and fewer relapses over a six-month period in patients with relapsing multiple sclerosis

Developing a Sealant Program: the Massachusetts Approach *

This paper describes the program structure and strategies being used by the Massachusetts Department of Public Health to promote the utilization of sealants. The program design includes four components: clinical demonstration, consumer education, professional education, and reimbursement. Eighteen Massachusetts neighborhood health centers and six local health departments are participating in the clinical demonstration component. Since March 1984, dental personnel from these sites have applied sealants to 4,398 schoolchildren. The promotional theme “Save Teeth: Seal Them” has been incorporated into brochures designed to increase knowledge and awareness of consumers. Curriculum materials have been developed to educate dentists and dental hygienists to apply sealants and understand the rationale and scientific basis for their use. Since January 1984, 18 sealant educational sessions have been conducted statewide for 630 dental providers. Information is being presented to third-party carriers, some of whom have subsequently adopted a policy to include reimbursement for sealants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65721/1/j.1752-7325.1986.tb03128.x.pd

Speciesistic Veganism: An Anthropocentric Argument

The paper proposes an anthropocentric argument for veganism based on a speciesistic premise that most carnists likely affirm: human flourishing should be promoted. I highlight four areas of human suffering promoted by a carnistic diet: (1) health dangers to workers (both physical and psychological), (2) economic dangers to workers, (3) physical dangers to communities around slaughterhouses, and (4) environmental dangers to communities-at-large. Consequently, one could ignore the well-being of non-human animals and nevertheless recognize significant moral failings in the current standard system of meat production

Seed size and its rate of evolution correlate with species diversification across angiosperms

Species diversity varies greatly across the different taxonomic groups that comprise the Tree of Life (ToL). This imbalance is particularly conspicuous within angiosperms, but is largely unexplained. Seed mass is one trait that may help clarify why some lineages diversify more than others because it confers adaptation to different environments, which can subsequently influence speciation and extinction. The rate at which seed mass changes across the angiosperm phylogeny may also be linked to diversification by increasing reproductive isolation and allowing access to novel ecological niches. However, the magnitude and direction of the association between seed mass and diversification has not been assessed across the angiosperm phylogeny. Here, we show that absolute seed size and the rate of change in seed size are both associated with variation in diversification rates. Based on the largest available angiosperm phylogenetic tree, we found that smaller-seeded plants had higher rates of diversification, possibly due to improved colonisation potential. The rate of phenotypic change in seed size was also strongly positively correlated with speciation rates, providing rare, large-scale evidence that rapid morphological change is associated with species divergence. Our study now reveals that variation in morphological traits and, importantly, the rate at which they evolve can contribute to explaining the extremely uneven distribution of diversity across the ToL.Gatsby Charitable Trust Wellcome Trust Sir Isaac Newton Trust BBSRC DTP grant to EF Miller (BB/M011194/1

Nafion Matrix and Ionic Domain Tuning for High-Performance Composite Proton Exchange Membranes

Although proton exchange membranes (PEMs) are widely deployed in an array of commercial applications, limitations linked to their proton conductivity, water retention, and gas permeability still limit ultimate device performance. While ex situ studies have shown additives can enhance membrane stability and mass transport, to date few have demonstrated that these performance enhancements are maintained when tested in commercially relevant electrochemical technologies, such as fuel cells or electrolyzers. Herein, a new multifunctional additive, 2D poly(triazine imide) (PTI), is demonstrated for composite PEMs, which is shown to boost proton conductivity by 37% under optimal high relative humidity (RH) conditions and 67% at low RHs. PTI also enables major improvements (over 55%) in both current and power densities in industrially relevant PEM fuel cells (PEMFCs). Most importantly, in situ and ex situ characterization suggests that the enhanced performance is due to polymer aggregate-PTI clusters that form with increasing 2D character and improved long-range connectivity, while acid-base interactions with pyridinic nitrogen facilitate the critical proton hopping mechanism at all RHs. Hence, this work offers both a new membrane concept with proven benefits for important electrochemical technologies, as well as design principles for future optimization of proton transport and water management within PEMs