Short-term post release mortality of skates (family Rajidae) discarded in a western North Atlantic commercial otter trawl fishery

a b s t r a c t Due to market and regulatory factors, Rajidae skates are routinely discarded by commercial otter trawlers in the western North Atlantic. Accounting for post-release mortality is therefore essential to total fishing mortality estimates, stock status and management of this group of fishes. However, despite a presumed species-specific range in tolerance, few studies have investigated the short-term post-release mortality among skates indigenous to the western North Atlantic following capture by mobile fishing gears, and never in the Gulf of Maine. This study addresses this shortfall for the prohibited thorny skate, Amblyraja radiate and smooth skate, Malacoraja senta, and the targeted winter skate, Leucoraja ocellata, and little skate, Leucoraja erinacea. Of 1288 skates evaluated, negligible immediate mortality was observed at the time of capture, even in relation to the largest catches and/or most prolonged tows. However, injury frequency was moderate, with highest levels in the smooth (60%) and thorny (52%) skates. Aside from the smooth skate (59%), 72 h mortality rates were low overall (19% across all species when accounting tow durations indicative of the fishery), with the winter skate (8%) exhibiting the lowest levels. Logistic regression modeling revealed tow duration as the most universal predictor of condition and 72 h mortality, while catch biomass, sex, temperature changes, and animal size also held influence in certain species. Although in general the studied species appear more resilient to trawl capture and handling than previously estimated, interspecific differences must be accounted for when managing this group

The pd <--> pi+ t reaction around the Delta resonance

The pd pi+ t process has been calculated in the energy region around the Delta-resonance with elementary production/absorption mechanisms involving one and two nucleons. The isobar degrees of freedom have been explicitly included in the two-nucleon mechanism via pi-- and rho-exchange diagrams. No free parameters have been employed in the analysis since all the parameters have been fixed in previous studies on the simpler pp pi+ d process. The treatment of the few-nucleon dynamics entailed a Faddeev-based calculation of the reaction, with continuum calculations for the initial p-d state and accurate solutions of the three-nucleon bound-state equation. The integral cross-section was found to be quite sensitive to the NN interaction employed while the angular dependence showed less sensitivity. Approximately a 4% effect was found for the one-body mechanism, for the three-nucleon dynamics in the p-d channel, and for the inclusion of a large, possibly converged, number of three-body partial states, indicating that these different aspects are of comparable importance in the calculation of the spin-averaged observables.Comment: 40 Pages, RevTex, plus 5 PostScript figure

Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy

Complement is activated in progressive multiple sclerosis cortical grey matter lesions

The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain and spinal cord. Inflammation is tightly linked with neurodegeneration, and it is the accumulation of neurodegeneration that underlies increasing neurological disability in progressive MS. Determining pathological mechanisms at play in MS grey matter is therefore a key to our understanding of disease progression

Array CGH Phylogeny: How accurate are Comparative Genomic Hybridization-based trees?

<p>Abstract</p> <p>Background</p> <p>Array-based Comparative Genomic Hybridization (CGH) data have been used to infer phylogenetic relationships. However, the reliability of array CGH analysis to determine evolutionary relationships has not been well established. In most CGH work, all species and strains are compared to a single reference species, whose genome was used to design the array. In the accompanying work, we critically evaluated CGH-based phylogeny using simulated competitive hybridization data. This work showed that a limited number of conditions, principally the tree topology and placement of the reference taxon in the tree, had a strong effect on the ability to recover the correct tree topology. Here, we add to our simulation study by testing the use of CGH as a phylogenetic tool with experimental CGH data from competitive hybridizations between <it>N. crassa </it>and other <it>Neurospora </it>species. In the discussion, we add to our empirical study of <it>Neurospora </it>by reanalyzing of data from a previous CGH phylogenetic analysis of the yeast <it>sensu stricto </it>complex.</p> <p>Results</p> <p>Array ratio data for <it>Neurospora </it>and related species were normalized with loess, robust spline, and linear ratio based methods, and then used to construct Neighbor-Joining and parsimony trees. These trees were compared to published phylogenetic analyses for <it>Neurospora </it>based on multilocus sequence analysis (MLSA). For the <it>Neurospora </it>dataset, the best combination of methods resulted in recovery of the MLSA tree topology less than half the time. Our reanalysis of a yeast dataset found that trees identical to established phylogeny were recovered only by pruning taxa - including the reference taxon - from the analysis.</p> <p>Conclusion</p> <p>Our results indicate that CGH data can be problematic for phylogenetic analysis. Success fluctuates based on the methods utilized to construct the tree and the taxa included. Selective pruning of the taxa improves the results - an impractical approach for normal phylogenetic analysis. From the more successful methods we make suggestions on the normalization and post-normalization methods that work best in estimating genetic distance between taxa.</p

The contribution of metacognitions and attentional control to decisional procrastination

Earlier research has implicated metacognitions and attentional control in procrastination and self-regulatory failure. This study tested several hypotheses: (1) that metacognitions would be positively correlated with decisional procrastination; (2) that attentional control would be negatively correlated with decisional procrastination; (3) that metacognitions would be negatively correlated with attentional control; and (4) that metacognitions and attentional control would predict decisional procrastination when controlling for negative affect. One hundred and twenty-nine participants completed the Depression Anxiety Stress Scale 21, the Meta-Cognitions Questionnaire 30, the Attentional Control Scale, and the Decisional Procrastination Scale. Significant relationships were found between all three attentional control factors (focusing, shifting, and flexible control of thought) and two metacognitions factors (negative beliefs concerning thoughts about uncontrollability and danger, and cognitive confidence). Results also revealed that decisional procrastination was significantly associated with negative affect, all measured metacognitions factors, and all attentional control factors. In the final step of a hierarchical regression analysis only stress, cognitive confidence, and attention shifting were independent predictors of decisional procrastination. Overall these findings support the hypotheses and are consistent with the Self-Regulatory Executive Function model of psychological dysfunction. The implications of these findings are discussed

A Single-Rate Context-Dependent Learning Process Underlies Rapid Adaptation to Familiar Object Dynamics

Motor learning has been extensively studied using dynamic (force-field) perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple-context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar object dynamics, however, the representations can be engaged based on visual context, and are updated by a single-rate process

Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues

Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. Intravenous injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2-targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues

Transcription Factor SP4 Is a Susceptibility Gene for Bipolar Disorder

The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018). To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029), and two of them (rs12673091, rs3735440) were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012) also displayed a significant association. The SNP7 (rs12673091) was therefore significantly associated in all three samples, and shared the same susceptibility allele (A) across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these psychiatric disorders