Student-To-Student Sexual Harassment: Legal Bases For School District And Individual Liability

Student-To-Student Sexual Harassment: Legal Bases For School District And Individual Liabilit

Multivalent antigen arrays exhibit high avidity binding and modulation of B cell receptor-mediated signaling to drive efficacy against experimental autoimmune encephalomyelitis

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biomacromolecules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.7b00335.A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgAPLP:LABL), consisting of a hyaluronic acid (HA) linear polymer backbone co-grafted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgAPLP:LABL, employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgAPLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using non-hydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule’s action at the cell surface to improve efficacy. ‘Click SAgA’ (cSAgAPLP:LABL) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgAPLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgAPLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgAPLP:LABL. Furthermore, c SAgAPLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgAPLP:LABL, achieving equivalent efficacy at one quarter of the dose. These results indicate that non-hydrolyzable conjugation increased the avidity of cSAgAPLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.NIH T32 GM008545Madison and Lila Self Graduate Fellowship at the University of KansasHoward Rytting pre-doctoral fellowship from the Department of Pharmaceutical Chemistry at the University of Kansa

Overall Splenectomy Rates Stable Despite Increasing Usage of Angiography in the Management of High-grade Blunt Splenic Injury

Objective: The purpose of this study was to understand the contemporary trends of splenectomy in blunt splenic injury (BSI) and to determine if angiography and embolization (ANGIO) may be impacting the splenectomy rate. Background: The approach to BSI has shifted to increasing use of nonoperative management, with a greater reliance on ANGIO. However, the impact ANGIO has on splenic salvage remains unclear with little contemporary data. Methods: The National Trauma Data Bank was used to identify patients 18 years and older with high-grade BSI (Abbreviated Injury Scale >II) treated at Level I or II trauma centers between 2008 and 2014. Primary outcomes included yearly rates of splenectomy, which was defined as early if performed within 6 hours of ED admission and delayed if greater than 6 hours, ANGIO, and mortality. Trends were studied over time with hierarchical regression models. Results: There were 53,689 patients who had high-grade BSI over the study period. There was no significant difference in the adjusted rate of overall splenectomy over time (24.3% in 2008, 24.3% in 2014, P value = 0.20). The use of ANGIO rapidly increased from 5.3% in 2008 to 13.5% in 2014 (P value < 0.001). Mortality was similar overtime (8.7% in 2008, 9.0% in 2014, P value = 0.33). Conclusion: Over the last 7 years, the rate of angiography has been steadily rising while the overall rate of splenectomy has been stable. The lack of improved overall splenic salvage, despite increased ANGIO, calls into question the role of ANGIO in splenic salvage on high-grade BSI at a national level

Self-organized Pattern Formation in Motor-Microtubule Mixtures

We propose and study a hydrodynamic model for pattern formation in mixtures of molecular motors and microtubules. The steady state patterns we obtain in different regimes of parameter space include arrangements of vortices and asters separately as well as aster-vortex mixtures and fully disordered states. Such stable steady states are observed in experiments in vitro. The sequence of patterns obtained in the experiments can be associated with smooth trajectories in a non-equilibrium phase diagram for our model.Comment: 11 pages Latex file, 2 figures include

The cost effectiveness of peginterferon alfa and ribavirin for the treatment of hepatitis C in children and young people

OBJECTIVES: To assess the cost-effectiveness of peginterferon ?-2a and peginterferon ?-2b in combination with ribavirin compared to best supportive care (BSC), for the treatment of chronic hepatitis C virus (HCV) in children and young people aged 3 to 17 years. METHODS: A Markov state-transition economic model of chronic HCV in children and young people was developed that extrapolated the impact of sustained virological response (SVR) on life expectancy, quality-adjusted life expectancy and lifetime costs. The model was adapted from one previously developed for adults. A systematic review was conducted of the clinical effectiveness of the treatments, and the health related quality of life for patients with hepatitis C. Uncertainty was explored through probabilistic and deterministic sensitivity analyses. RESULTS: Seven studies were identified that were relatively small and of generally poor quality. Estimates of SVR were similar for for peginterferon ?-2a (60%) and peginterferon ?-2b (58%) was similar, whilst the SVR for no treatment was assumed to be zero. From this model, peginterferon alfa (?-2a or ?-2b) in combination with ribavirin was more effective and cheaper than BSC. Sensitivity analyses suggest that the results were generally robust to all changes to the structural assumptions and input parameters. The model results were most sensitive to changes to the discount rate, time horizon, SVR and baseline fibrosis of the cohort. CONCLUSIONS: Treatment of children and young people with peginterferon alfa (?-2a or ?-2b) and ribavirin may be an effective therapy. Peginterferon alfa (?-2a or ?-2b) in combination with ribavirin is cost-effective compared with BSC. However, the available evidence is of poor quality. The views expressed in this paper are those of the authors and do not necessarily represent the views or policies of the UK HTA programme or Department of Health

Infliximab for the treatment of adults with psoriasis. Evidence Review Group Report for NICE's Single Technology Appraisal process

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of infliximab for the treatment of moderate to severe plaque psoriasis, in accordance with the licensed indication, based on the evidence submission from Schering-Plough to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer's definition of the decision problem were severity [Psoriasis Area and Severity Index (PASI) score], remission rates, relapse rates and health-related quality of life. The main evidence in the submission comes from four randomised controlled trials (RCT) comparing infliximab with placebo and eight RCTs comparing either etanercept or efalizumab with placebo. At week 10, patients on infliximab had a significantly higher likelihood of attaining a reduction in PASI score than placebo patients. There were also statistically significant differences between infliximab and placebo in the secondary outcomes. In the comparator trials both the efalizumab and etanercept arms included a significantly higher proportion of patients who achieved a reduction in PASI score at week 12 than the placebo arms. No head-to-head studies were identified directly comparing infliximab with etanercept or efalizumab. The manufacturer carried out an indirect comparison, but the ERG had reservations about the comparison because of the lack of information presented and areas of uncertainty in relation to the included data. The economic model presented by the manufacturer was appropriate for the disease area and given the available data. The cost-effectiveness analysis estimates the mean length of time that an individual would respond to infliximab compared with continuous etanercept and the utility gains associated with this response. The base-case incremental cost-effectiveness ratio (ICER) for infliximab compared with continuous etanercept for patients with severe psoriasis was £26,095 per quality-adjusted life-year. A one-way sensitivity analysis, a scenario analysis and a probabilistic sensitivity analysis were undertaken by the ERG. The ICER is highly sensitive to assumptions about the costs and frequency of inpatient stays for non-responders of infliximab. The guidance issued by NICE in August 2007 as a result of the STA states that infliximab within its licensed indication is recommended for the treatment of adults with very severe plaque psoriasis, or with psoriasis that has failed to respond to standard systematic therapies. Infliximab treatment should be continued beyond 10 weeks in people whose psoriasis has shown an adequate response to treatment within 10 weeks. In addition, when using the Dermatology Life Quality Index (DLQI), care should be taken to take into account the patient's disabilities, to ensure DLQI continues to be an accurate measure

Sediment Quality Triad assessment in Kachemak Bay: characterization of soft bottom benthic habitats and contaminant bioeffects assessment

A baseline environmental characterization of the inner Kachemak Bay, Alaska was conducted using the sediment quality triad approach based on sediment chemistry, sediment toxicity, and benthic invertebrate community structure. The study area was subdivided into 5 strata based on geophysical and hydrodynamic patterns in the bay (eastern and western intertidal mud flats, eastern and western subtidal, and Homer Harbor). Three to seven locations were synoptically sampled within each stratum using a stratified random statistical design approach. Three sites near the village of Port Graham and two sites in the footprint of a proposed Homer Harbor expansion were also collected for comparison. Concentrations of over 120 organic and metallic contaminants were analyzed. Ambient toxicity was assessed using two amphipod bioassays. A detailed benthic community condition assessment was performed. Habitat parameters (depth, salinity, temperature, dissolved oxygen, sediment grain size, and organic carbon content) that influence species and contaminant distribution were also measured at each sampling site. Sediments were mostly mixed silt and sand; characteristic of high energy habitats, with pockets of muddy zones. Organic compounds (PAHs, DDTs, PCBs, cyclodienes, cyclohexanes) were detected throughout the bay but at relatively low concentrations. Tributyltin was elevated in Homer Harbor relative to the other strata. With a few exceptions, metals concentrations were relatively low and probably reflect the input of glacial runoff. Relative to other sites, Homer Harbor sites were shown to have elevated concentrations of metallic and organic contaminants. The Homer Harbor stratum however, is a deep, low energy depositional environment with fine grained sediment. Concentrations of organic contaminants measured were five to ten times higher in the harbor sites than in the open bay sites. Concentration of PAHs is of a particular interest because of the legacy of oil spills in the region. There was no evidence of residual PAHs attributable to oil spills, outside of local input, beyond the confines of the harbor. Concentrations were one to ten times below NOAA sediment quality guidelines. Selected metal concentrations were found to be relatively elevated compared to other data collected in the region. However, levels are still very low in the scale of NOAA’s sediment quality guidelines, and therefore appear to pose little or no ecotoxicity threat to biota. Infaunal assessment showed a diverse assemblage with more than 240 taxa recorded and abundances greater than 3,000 animals m-22 in all but a few locations. Annelid worms, crustaceans, snails, and clams were the dominant taxa accounting for 63 %, 19%, 5%, and 7 % respectively of total individuals. Specific benthic community assemblages were identified that were distributed based on depth and water clarity. Species richness and diversity was lower in the eastern end of the bay in the vicinity of the Fox River input. Abundance was also generally lower in the eastern portion of the study area, and in the intertidal areas near Homer. The eastern portions of the bay are stressed by the sediment load from glacial meltwater. Significant toxicity was virtually absent. Conditions at the sites immediately outside the existing Homer Harbor facility did not differ significantly from other subtidal locations in the open Kachemak Bay. The benthic fauna at Port Graham contained a significant number of species not found in Kachemak Bay. Contaminant conditions were variable depending on specific location. Selected metal concentrations were elevated at Port Graham and some were lower relative to Kachemak Bay, probably due to local geology. Some organic contaminants were accumulating at a depositional site

Extracorporeal life support in pediatric trauma: a systematic review

Introduction Extracorporeal membrane oxygenation (ECMO) was once thought to be contraindicated in trauma patients, however ECMO is now used in adult patients with post-traumatic acute respiratory distress syndrome (ARDS) and multisystem trauma. Despite acceptance as a therapy for the severely injured adult, there is a paucity of evidence supporting ECMO use in pediatric trauma patients. Methods An electronic literature search of PubMed, MEDLINE, and the Cochrane Database of Collected Reviews from 1972 to 2018 was performed. Included studies reported on ECMO use after trauma in patients ≤18 years of age and reported outcome data. The Institute of Health Economics quality appraisal tool for case series was used to assess study quality. Results From 745 studies, four met inclusion criteria, reporting on 58 pediatric trauma patients. The age range was <1–18 years. Overall study quality was poor with only a single article of adequate quality. Twenty-nine percent of patients were cannulated at adult centers, the remaining at pediatric centers. Ninety-one percent were cannulated for ARDS and the remaining for cardiovascular collapse. Overall 60% of patients survived and the survival rate ranged from 50% to 100%. Seventy-seven percent underwent venoarterial cannulation and the remaining underwent veno-venous cannulation. Conclusion ECMO may be a therapeutic option in critically ill pediatric trauma patients. Consideration should be made for the expansion of ECMO utilization in pediatric trauma patients including its application for pediatric patients at adult trauma centers with ECMO capabilities

Sediment quality triad assessment in Kachemak Bay: characterization of soft bottom benthic habitats and contaminant bioeffects assessment condensed. A NOAA/NOS/NCCOS/CCMA Special Report

A baseline environmental characterization of the inner Kachemak Bay, Alaska was conducted using standardized National Status and Trends Bioeffects Program methods. Three sites near the village of Port Graham were also sampled for comparison. Concentrations of over 120 organic and metallic contaminants were analyzed. Ambient toxicity was assessed using two bioassays. A detailed benthic community condition assessment was performed. Habitat parameters (e.g. depth, salinity, temperature, dissolved oxygen, sediment grain size, and organic carbon content) that influence species and contaminant distribution were also measured at each sampling site. The following is the synopsis of findings • Sediments were mostly mixed silt and sand with pockets of muddy zones. Organic compounds (PAHs, DDTs, PCBs, chlorinated pesticides) were detected throughout the bay but at relatively low concentrations. With some exceptions, metals concentrations were relatively low and probably reflect the input of glacial runoff. • Homer Harbor had elevated concentrations of metallic and organic contaminants. Concentrations of organic contaminants measured were five to ten times higher in the harbor sites than in the open bay sites. Tributyltin was elevated in Homer Harbor relative to the other areas. • There was no evidence of residual PAHs attributable to oil spills, outside of local input in the confines of the harbor. • The benthic community is very diverse. Specific community assemblages were distributed based on depth and water clarity. Species richness and diversity was lower in the eastern end of the bay in the vicinity of the Fox River input. Abundance was also generally lower in the eastern portion of the study area, and in the intertidal areas near Homer. The eastern portions of the bay are stressed by the sediment load from glacial meltwater. • Significant toxicity was virtually absent. • The benthic fauna at Port Graham contained a significant number of species not found in Kachemak Bay. • Selected metal concentrations were elevated at Port Graham relative to Kachemak Bay, probably due to local geology. Organic contaminants were elevated at a site south of the village

The Community Environmental Monitoring Program in the 21st Century: The Evolution of a Monitoring Network

This paper focuses on the evolution of the various operational aspects of the Community Environmental Monitoring Program (CEMP) network following the transfer of program administration from the U.S. Environmental Protection Agency (EPA) to the Desert Research Institute (DRI) of the Nevada System of Higher Education in 1999-2000. The CEMP consists of a network of 29 fixed radiation and weather monitoring stations located in Nevada, Utah, and California. Its mission is to involve stakeholders directly in monitoring for airborne radiological releases to the off site environment as a result of past or ongoing activities on the Nevada Test Site (NTS) and to make data as transparent and accessible to the general public as feasible. At its inception in 1981, the CEMP was a cooperative project of the U.S. Department of Energy (DOE), DRI, and EPA. In 1999-2000, technical administration of the CEMP transitioned from EPA to DRI. Concurrent with and subsequent to this transition, station and program operations underwent significant enhancements that furthered the mission of the program. These enhancements included the addition of a full suite of meteorological instrumentation, state-of-the-art electronic data collectors, on-site displays, and communications hardware. A public website was developed. Finally, the DRI developed a mobile monitoring station that can be operated entirely on solar power in conjunction with a deep-cell battery, and includes all meteorological sensors and a pressurized ion chamber for detecting background gamma radiation. Final station configurations have resulted in the creation of a platform that is well suited for use as an in-field multi-environment test-bed for prototype environmental sensors and in interfacing with other scientific and educational programs. Recent and near-future collaborators have included federal, state, and local agencies in both the government and private sectors. The CEMP also serves as a model for other programs wishing to involve stakeholders with a meaningful role in the process of monitoring and data collection