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During the COVID-19 pandemic, there has been considerable research on how regional and country-level forecasting can be used to anticipate required hospital resources. We add to and build on this work by focusing on ward-level forecasting and planning tools for hospital staff during the pandemic. We present an assessment, validation, and deployment of a working prototype forecasting tool used within a modified Traffic Control Bundling (TCB) protocol for resource planning during the pandemic. We compare statistical and machine learning forecasting methods and their accuracy at one of the largest hospitals (Vancouver General Hospital) in Canada against a medium-sized hospital (St. Paul’s Hospital) in Vancouver, Canada through the first three waves of the COVID-19 pandemic in the province of British Columbia. Our results confirm that traditional statistical and machine learning (ML) forecasting methods can provide valuable ward-level forecasting to aid in decision-making for pandemic resource planning. Using point forecasts with upper 95% prediction intervals, such forecasting methods would have provided better accuracy in anticipating required beds on COVID-19 hospital units than ward-level capacity decisions made by hospital staff. We have integrated our methodology into a publicly available online tool that operationalizes ward-level forecasting to aid with capacity planning decisions. Importantly, hospital staff can use this tool to translate forecasts into better patient care, less burnout, and improved planning for all hospital resources during pandemics.

ObjectiveTranslocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy.MethodsFive subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice—on average 8 weeks apart—using a second generation TSPO targeting radioligand, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers.ResultsThe mean (± SD) of the volume of distribution (VT), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (−1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, VT of [11C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region.ConclusionWhen using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in VT represents the clinical outcome.

Translating genome-wide association loci to therapies requires knowledge of the causal genes, their directionality of effect and the cell-types in which they act. To infer these relationships in the human brain, we implemented Mendelian randomisation using single cell-type expression quantitative trait loci (eQTLs) as genetic anchors. Expression QTLs were mapped across 8 major cell-types in brain tissue exclusively ascertained from donors with no history of brain disease. We report evidence for a causal association between the change in expression of 118 genes and one or more of 16 brain phenotypes, revealing candidate targets for risk mitigation and opportunities for shared preventative therapeutic strategies. We highlight key causal genes for neurodegenerative and neuropsychiatric disease and for each, we report its cellular context and the therapeutic directionality required for risk mitigation. Our use of control samples establishes a new resource for the causal interpretation of GWAS risk alleles for human brain phenotypes.

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied—inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic foetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation.

Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin by immune cells, which are thought to be the main drivers of MS susceptibility. We found that immune genes exhibit a primed chromatin state in single mouse and human OLG in a non-disease context, compatible with transitions to immune-competent states in MS. We identified BACH1 and STAT1 as transcription factors involved in immune gene regulation in oligodendrocyte precursor cells (OPCs). A subset of immune genes presents bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon gamma (IFN-g) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse and human OLG. Treatment of mouse OPCs with IFN-g leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Thus, the susceptibility for MS may involve OLG, which therefore constitutes novel targets for immunological based therapies for MS.

Summary Here, with the example of common copy number variation (CNV) in the TSPAN8 gene, we present an important piece of work in the field of CNV detection, that is, CNV association with complex human traits such as 1H NMR metabolomic phenotypes and an example of functional characterization of CNVs among human induced pluripotent stem cells (HipSci). We report TSPAN8 exon 11 (ENSE00003720745) as a pleiotropic locus associated with metabolomic regulation and show that its biology is associated with several metabolic diseases such as type 2 diabetes (T2D) and cancer. Our results further demonstrate the power of multivariate association models over univariate methods and define metabolomic signatures for variants in TSPAN8., Graphical abstract, Highlights • We demonstrate neuro-exocrine axis for type 2 diabetes and metabolic regulation • Human induced pluripotent stem cells was successfully applied for disease modeling • We note germline CNV deletions are reversed to somatic amplifications • We characterizedgene variants associated with obesity with greater odds ratio than FTO SNPs, Biological sciences; Genetics and physiology; Molecular biology; Endocrinology ; Cancer systems biology

Objective: Resistance to anti-seizure medications (ASMs) presents a significant hurdle in the treatment of people with epilepsy. Genetic markers for resistance to individual ASMs could support clinicians to make better-informed choices for their patients. In this study, we aimed to elucidate whether the response to individual ASMs was associated with common genetic variation.Methods: A cohort of 3,649 individuals of European descent with epilepsy was deeply phenotyped and underwent single nucleotide polymorphism (SNP)-genotyping. We conducted genome-wide association analyses (GWASs) on responders to specific ASMs or groups of functionally related ASMs, using non-responders as controls. We performed a polygenic risk score (PRS) analyses based on risk variants for epilepsy and neuropsychiatric disorders and ASM resistance itself to delineate the polygenic burden of ASM-specific drug resistance.Results: We identified several potential regions of interest but did not detect genome-wide significant loci for ASM-specific response. We did not find polygenic risk for epilepsy, neuropsychiatric disorders, and drug-resistance associated with drug response to specific ASMs or mechanistically related groups of ASMs.Significance: This study could not ascertain the predictive value of common genetic variants for ASM responder status. The identified suggestive loci will need replication in future studies of a larger scale.

Previous studies on voting bias in competitive awards have not fully considered the role of cultural similarity. Using data for the Best FIFA Men’s Player Award, we evaluate the extent of voting bias in this Award using three cultural similarity factors (cultural distance, cultural clusters, and collectivism), six established in-group factors (nationality, club, league, geography, ethnicity, religion, and language) and the impartiality of the voter’s country. Using statistical and econometric methods, we find that voter-player cultural similarity is positively associated with voting bias and find no evidence of impartiality when it comes to cultural or national ties. We also find that media voters are less biased than captain voters and coach voters, and that coaches are less biased than captains.

EBioMedicine 72, 103588 (2021). doi:10.1016/j.ebiom.2021.103588, Published by Elsevier, Amsterdam [u.a.]

Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.

Here, with the example of common copy number variation (CNV) in the TSPAN8 gene, we present an important piece of work in the field of CNV detection, CNV association with complex human traits such as 1H NMR metabolomic phenotypes and an example of functional characterization of CNVs among human induced pluripotent stem cells (HipSci). We report TSPAN8 exon 11 as a new locus associated with metabolomic regulation and show that its biology is associated with several metabolic diseases such as type 2 diabetes (T2D), obesity and cancer. Our results further demonstrate the power of multivariate association models over univariate methods and define new metabolomic signatures for several new genomic loci, which can act as a catalyst for new diagnostics and therapeutic approaches.

Anecdotally, many students are disadvantaged by gaps in their High School and early college Algebra, Trigonometry and Geometry. The authors piloted a project developing a platform in Canvas with modules presenting select topics, using both material at the High School level in the public domain, and new tutorial videos to cover the assumed background knowledge at the college level. Post- and pre-tests were administered to control groups and treatment groups to determine the efficacy of the offerings. Statistical analysis showed that the implementation of the platform as part of the course did not improve student performance in the targeted topics. However, a number of interesting results emerged from the study regarding surprising areas of weakness and general student responses to teaching methods.

The measurement of spatiotemporal gait parameters is commonly utilized to assess gait in healthy and injured individuals. The OptoGait system is a portable system and can be mounted to a treadmill to collect data in a clinical, training, or research setting. The purpose of this method comparison study was to examine the agreement of spatiotemporal gait parameters calculated by the OptoGait compared to an instrumented treadmill system during running. Thirty healthy runners ran on an instrumented treadmill with the OptoGait 1-m system mounted along the treadmill platform. Spatiotemporal running variables of step rate, step length, and contact time were calculated during the final minute of treadmill running. The level of agreement between the OptoGait and treadmill was analyzed using intraclass correlation coefficients [ICC (2,3)] for step rate, step length, and contact time. Step rate and step length demonstrated excellent agreement. Contact time demonstrated good agreement. Intraclass correlation coefficients for spatiotemporal parameters ranged from 0.83 to 0.99. The OptoGait demonstrated good to excellent agreement in the evaluation of running step rate, step length, and contact time and should be considered for use in clinical, training, or research settings.

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins. ispartof: NEUROBIOLOGY OF AGING vol:92 ispartof: location:United States status: published

In this paper, we introduce a novel way of understanding organizational resilience. We suggest that organizational resilience can be profitably viewed as an evolutionary process in which organizations adapt their configurations in response to changes in two external conditions — disturbance and munificence. Focusing on the contexts of manufacturing and operations management, we begin by explaining the concepts of organizational configuration and resilience. We then present a framework that views resilience-driven configuration change as an evolutionary process of variation, selection, and retention for a population of firms. The final component of this framework is the use of the cladistic method of classification to develop a hypothesis of the branching order of configuration change. We conclude the paper by presenting a typology that shows how different levels of munificence and disturbance combine to produce two types of adaptive resilience (cladogenetic and anagenetic) and one type of non-adaptive resilience (inertia). We also explain how phylograms can be used to indicate the amount of time separating different organizational configurations.

This work evaluates the applicability of computational electromagnetic methods for the determination of Cavity Calibration Factors for aircraft weapon bays. Cavity Calibration Factors provide a prediction of maximum expected electrical field levels in a weapon bay for evaluating EMC, including hazards of electromagnetic radiation to ordnance. A generalized geometry is created with traits similar to an aircraft bay. The Transmission Line Matrix method is used to simulate the response of the bay across two frequency bands; 800–2500 MHz using a near field source and 5300–5900 MHz using a tuned dipole. Results are evaluated for chi-squared distribution with six degrees of freedom and the total number of modes contained at four frequencies; 915, 1830, 2250, and 5600 MHz.

The retreat of the Paratethys Sea in the Middle to Late Miocene left behind a series of intermontane lakes across Central Europe. Ancient Lake Pannon, which existed in present-day Hungary and surrounding countries, was gradually filled in by fluvial sedimentation from 10 to 4 Ma. This infilling allowed for the migration of mammals such as the horse Hippotherium into the Pannonian Basin System (PBS). Stable carbon and oxygen isotope records from Hippotherium are used here to reconstruct changing environmental conditions of the Late Miocene in this region. Our emphasis is on understanding the vegetation and surface water of the basin because these in turn affected the isotopic composition of Lake Pannon. We analyzed the enamel of 68 Hippotherium teeth from 23 localities in the PBS for carbon and oxygen isotope composition. Carbon isotope records indicate that Hippotherium in the central regions of the basin were feeding in more open habitats than those in the northwest. We find no evidence of the expansion of C4 grasses into the PBS. Oxygen and carbon isotope values from the Vienna Basin (NW part of the PBS) generally covary, whereas those from more central regions do not. The oxygen values of the central PBS are generally lower than those of the Vienna Basin. These data suggest that the interior of the PBS was generally dry, which forced Hippotherium to use water sources that were not strongly evaporated, such as rivers originating from outside the basin. The dry interior was likely caused by a rain shadow east of the Alps and north of the Dinarides. Consequently, much of the surface inflow into Lake Pannon would have been influenced by runoff from high elevations around or outside the basin. By understanding the terrestrial environment, better constraints can be placed on lake conditions in future work.

Marketing instructors using simulation games as a way of inducing some realism into a marketing course are faced with many dilemmas. Two important quandaries are the optimal size of groups and how much of the students’ time should ideally be devoted to the game. Using evidence from a very large sample of teams playing a simulation game, the study described here seeks to answer two fundamental questions: What effects on performance does group size have? And, is it possible for groups to spend too much time on decision making? The results indicate that performance increases in line with group size until teams have five members, and then tapers off. Furthermore, performance is shown to rise as time spent on decision making increases, up to a point, after which additional time spent on the game is shown to detract from performance. Implications for marketing instructors are discussed.

Crop yield forecast models for barley, canola and spring wheat grown on the Canadian Prairies were developed using vegetation indices derived from satellite data and machine learning methods. Hierarchical clustering was used to group the crop yield data from 40 Census Agricultural Regions (CARs) into several larger regions for building the forecast models. The Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) derived from the Moderate-resolution Imaging Spectroradiometer (MODIS), and NDVI derived from the Advanced Very High Resolution Radiometer (AVHRR) were considered as predictors for crop yields. Multiple linear regression (MLR) and two nonlinear machine learning models – Bayesian neural networks (BNN) and model-based recursive partitioning (MOB) – were used to forecast crop yields, with various combinations of MODIS-NDVI, MODIS-EVI and NOAA-NDVI as predictors. Crop yield forecasts made using predictors from July and earlier were evaluated by the cross-validated mean absolute error skill score (in reference to climatological forecasts) during 2000–2011. While MODIS-NDVI was found to be the most effective predictor for all three crops, having MODIS-EVI as an additional predictor enhanced the forecast skills. While MLR, BNN and MOB all showed significantly higher skills than climatological forecasts for all three crops, barley was the only case where the nonlinear BNN and MOB models showed slightly higher skills than MLR. The lack of skill improvement by nonlinear models over MLR is likely due to the short (12 years) record available for MODIS data, which limits our study to 2000–2011, with very low yields coming from a single severe drought year (2002).

As printed circuit boards have decreased in size and increased in complexity (i.e. number of layers, number of installed components, speed of busses, etc.), access to test resources (i.e. probe points) necessary for sufficient printed circuit board test has diminished. The use of intrusive test methods such as in-circuit testers, manufacturing defect analyzers, and flying probe testers entails many downsides. Each method requires access to printed circuit board probe points, the equipment necessary to facilitate each intrusive method can take up large amounts of floor space in a manufacturing facility and can be costly to operate and maintain (i.e. technician time, fixture origination and fixture revision due to printed circuit board redesign). Because of these and more downsides, non-intrusive board test has emerged as a cost-effective alternative to intrusive test or as a cost-reducing complement where intrusive test methods are still used.

BACKGROUND: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.METHODS: For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes.FINDINGS: Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41-4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05-2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 [95% CI 1·02-2·08]; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors.INTERPRETATION: Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy.FUNDING: EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).

Shoulder dislocation and subsequent instability is a common problem in young athletes. Though it is not uncommon to attempt nonoperative rehabilitation in the early going, reinjury rates are high, particularly with contact sport athletes. As a result, many athletes will undergo a primary repair of one, or multiple, glenohumeral ligaments that make up the anterior shoulder capsule. This paper presents phases of rehabilitation from the preoperative stage up to returning to play. Criteria for phase progression are included, along with examples of common exercises and themes for each phase that allow the physical therapist to consider when working with patients who have had this type of shoulder surgery, allowing them to return to full function with low risk of reinjury.

Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAStatistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAFunctionally relevant variants in genes encoding GABAEuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).

This paper describes the process through which an electromagnetic environment model of the F-15E was found to be sufficient for use in aircraft and store compatibility recommendations. Controlled radio frequency measurements were taken from a U.S. Air Force aircraft and compared directly to the predicted quantities using computational electromagnetics. This paper elaborates on the assumptions made and potential sources of error in both physical test and simulation, and the influence they have on achieving the proposed success criteria for model verification.

Knowing the electric fields that may be encountered in the proximity of large array antennas is critical for determining the compatibility of equipment near that antenna. Given a few parameters such as effective area, frequency and power, the electric field magnitudes at any given range can be approximated within easily determined boundaries using well-understood electromagnetic theory. This paper describes such a method and evaluates its results against simulated fields radiated from simple arrays with similar dimensions.

The diagnosis of an intra-articular osteoid osteoma can be a challenging and lengthy process, with reports of delayed diagnosis of greater than 2 years. In the young, athletic patient with an atraumatic onset of groin pain, an overuse injury or muscle strain is the most likely etiology. However, an overuse injury of femoral neck stress fracture must be identified because of the potentially disastrous outcome of fracture completion. The similar clinical presentation of a femoral neck stress fracture and intra-articular osteoid osteoma of the femoral neck can further delay the diagnosis of the osteoid osteoma. In a patient with these differential diagnoses that do not improve with a period of nonweightbearing activity, a more intensive workup must ensue. The purpose of this case report is to describe the initial presentations, subsequent follow-up, and imaging findings leading to the diagnosis of osteoid osteoma as well as to differentiate an osteoid osteoma from femoral neck stress injuries.

Environmental and economic evidence is increasingly supporting the need for better analytical tools for evaluating the recovery of consumer products. In response, we present a novel mathematical model for determining what we call the Optimal Recovery Plan (ORP) for any given product. The ORP is based on an evaluation and optimization of the economics of remanufacturing consumer products versus demanufacturing in the context of Extended Producer Responsibility (EPR) legislation, a driving force behind the adoption remanufacturing initiatives by firms. We provide an illustrative application of the model and then discuss its implications for scholars and practitioners concerned with sustainable business development.

Convulsive status epilepticus (CSE) is a common neurological emergency with significant morbidity and mortality. We developed a CSE management protocol for a tertiary neurosciences centre with the aim of standardizing practice and increasing the likelihood of favourable outcome. To do this we undertook a questionnaire-based audit of current management principles in A&E staff (n=24), as well as a retrospective case-based audit of 3-months of acute seizure presentations in the same department (n=-103). We identified variable understanding of optimal management, lack of awareness/availability of informative resources and subsequent suboptimal management. Following this we developed and implemented a trust-wide CSE management protocol based on national guidance, literature review and the local expert opinion of neurology consultants and neuroscience pharmacists. The protocol covers early, established and refractory CSE and includes pharmaceutical management, important investigations/observations and who to involve and when. The protocol was published on the trust Intranet and summary flowchart posters were displayed in A&E. We organised teaching sessions for A&E staff and those involved in acute medicine. Though not complete at time of abstract submission, we intend to re-audit CSE management in the near future, assessing protocol adherence and will also present the results of this.

Summary Background Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. Methods We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. Findings We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7–3·2, p=9·1 × 10 −8 ; familial non-acquired focal epilepsy 3·6, 2·7–4·9, p=1·1 × 10 −17 ). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10 −8 ) that were lower than expected from a random sampling of genes. Interpretation We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. Funding National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK.

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de nova mutations, including de novo mutations in DNM1 in five individuals and de nova mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de nova mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 x 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de nova mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction.

While advanced diagnostic imaging is a large contributor to the growth in health care costs, direct-access to physical therapy is associated with decreased rates of diagnostic imaging. No study has systematically evaluated with evidence-based criteria the appropriateness of advanced diagnostic imaging, including magnetic resonance imaging (MRI), when ordered by physical therapists. The primary purpose of this study was to describe the appropriateness of magnetic resonance imaging (MRI) or magnetic resonance arthrogram (MRA) exams ordered by physical therapists in a direct-access sports physical therapy clinic.Retrospective observational study of practice.Greater than 80% of advanced diagnostic imaging orders would have an American College of Radiology (ACR) Appropriateness Criteria rating of greater than 6, indicating an imaging order that is usually appropriate.A 2-year retrospective analysis identified 108 MRI/MRA examination orders from four physical therapists. A board-certified radiologist determined the appropriateness of each order based on ACR appropriateness criteria. The principal investigator and co-investigator radiologist assessed agreement between the clinical diagnosis and MRI/surgical findings.Knee (31%) and shoulder (25%) injuries were the most common. Overall, 55% of injuries were acute. The mean ACR rating was 7.7; scores from six to nine have been considered appropriate orders and higher ratings are better. The percentage of orders complying with ACR appropriateness criteria was 83.2%. Physical therapist's clinical diagnosis was confirmed by MRI/MRA findings in 64.8% of cases and was confirmed by surgical findings in 90% of cases.Physical therapists providing musculoskeletal primary care in a direct-access sports physical therapy clinic appropriately ordered advanced diagnostic imaging in over 80% of cases. Future research should prospectively compare physical therapist appropriateness and utilization to other groups of providers and explore the effects of physical therapist imaging privileging on outcomes.Diagnosis, Level 3.

A 20-year-old female rugby player was injured when an opponent landed on her leg during a match. Twelve days after injury, the team's certified athletic trainer referred the patient to a physical therapist due to continued pain. Following fluoroscopic imaging, which was utilized by the physical therapist because standard radiographs were unavailable in close proximity, she was referred for radiographs, which demonstrated a midfibular diaphyseal fracture. J Orthop Sports Phys Ther 2016;46(7):608. doi:10.2519/jospt.2016.0411.

The objective of this study was to investigate the efficacy and safety of adjunctive lanicemine (NMDA channel blocker) in the treatment of major depressive disorder (MDD) over 12 weeks. This phase IIb, randomized, parallel-arm, double-blind, placebo-controlled study was conducted at 49 centers in four countries between December 2011 and August 2013 in 302 patients aged 18–70 years, meeting criteria for single episode or recurrent MDD and with a history of inadequate treatment response. Patients were required to be taking an allowed antidepressant for at least four weeks prior to screening. Patients were randomized equally to receive 15 double-blind intravenous infusions of adjunctive lanicemine 50 mg, lanicemine 100 mg, or saline over a 12-week course, in addition to ongoing antidepressant. The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 6. Secondary efficacy outcome variables included change in MADRS score from baseline to week 12, response and remission rates, and changes in Clinical Global Impression scale, Quick Inventory of Depressive Symptomology Self-Report score, and Sheehan Disability Scale score. Of 302 randomized patients, 240 (79.5%) completed treatment. Although lanicemine was generally well tolerated, neither dose was superior to placebo in reducing depressive symptoms on the primary end point or any secondary measures. There was no significant difference between lanicemine and placebo treatment on any outcome measures related to MDD. Post hoc analyses were performed to explore the possible effects of trial design and patient characteristics in accounting for the contrasting results with a previously reported trial.

The Chemistry Outreach Program (ChOP) of Virginia Tech was a university-based outreach program that addressed the needs of high school chemistry classes in underfunded rural and inner-city school districts. The primary features of ChOP were a mobile chemistry laboratory (MCL), a shipping-based outreach program (ChemKits), and teacher workshops. ChOP targeted schools that lacked basic chemistry equipment and resources, as well as schools where science teachers had limited training in chemistry. The MCL, a fully equipped chemistry laboratory in a 78-foot-long tractor–trailer, visited high school chemistry classes on a regularly scheduled basis. From 2000 to 2004, the MCL served 38 high schools in which 9100 students performed 36,200 experiments. ChemKits, working in concert with the MCL, resulted in an additional 23,450 experiments conducted by students in 33 high schools from 2002 to 2004 and 17 high schools in 2004 to 2005. Teachers attended ChOP workshops in the summer prior to using the MCL or ChemKits ...

Research evidence points to the existence of racial-ethnic disparities in both access to and quality of mental health services for African Americans with panic disorder. Current panic disorder evaluation and treatment paradigms are not responsive to the needs of many African Americans. The primary individual, social, and health-care system factors that limit African Americans' access to care and response to treatment are not well understood. Low-income African American women with panic disorder participated in a series of focus-group sessions designed to elicit (1) their perspectives regarding access and treatment barriers and (2) their recommendations for designing a culturally consistent panic treatment program. Fear of confiding to others about panic symptoms, fear of social stigma, and lack of information about panic disorder were major individual barriers. Within their social networks, stigmatizing attitudes toward mental illness and the mentally ill, discouragement about the use of psychiatric medication, and perceptions that symptoms were the result of personal or spiritual weakness had all interfered with the participants' treatment seeking efforts and contributed to a common experience of severe social isolation. None of the focus-group members had developed fully effective therapeutic relationships with either medical or mental health providers. They described an unmet need for more interactive and culturally authentic relationships with treatment providers. Although the focus-group sessions were not intended to be therapeutic, the women reported that participation in the meetings had been an emotionally powerful and beneficial experience. They expressed a strong preference for the utilization of female-only, panic disorder peer-support groups as an initial step in the treatment/recovery process. Peer-support groups for low-income African American women with panic disorder could address many of the identified access and treatment barriers.

Eating disorders are a particular problem for college students, as well as college athletes and military personnel. We examined the incidence, prevalence, and risk of eating disorders at the United States Military Academy (USMA) over a 7-year period (total population 12,731 cadets). The incidence per year for females was 0.02% for anorexia, 0.17% for bulimia, and 0.17% for eating disorders not otherwise specified (EDNOS) and for males was 0.0% for anorexia, 0.003% for bulimia, and 0.02% for eating disorders not otherwise specified. The total prevalence of diagnosed eating disorders for females was 5% and for males was 0.1%. For females over the 7-year period, we found a prevalence of 0.2% for anorexia, 1.2% for bulimia, 1.2% for eating disorders not otherwise specified, and for males we found a prevalence of 0.0% for anorexia, 0.02% for bulimia, and 0.03% for eating disorders not otherwise specified. Nineteen percent of females and 2% of males scored a 20 or higher on the Eating Attitudes Test (EAT)-26 survey indicating they were at risk for developing an eating disorder. We conclude that the prevalence of eating disorders at USMA is comparable to civilian colleges.

A unique gated cathode structure for a Carbon Nanotube-based field emission display has been designed and built. This structure optimizes the electron beam profiles so as to assure high anode electron efficiency and a good color gamut without requiring specific focusing electrodes or structure. A computer simulation written to analyze and aid with the design shows good correlation with the experimental data and also helps to predict design margins. A full color frit-sealed display built with the approach demonstrates an excellent color gamut of the phosphor, and the model predicts avenues for increasing the color gamut further.

Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy. A total of 82 patients who had previously undergone detailed neuropsychological assessment were genotyped for single nucleotide polymorphisms (SNPs) across the NRSF and BDNF genes. Putatively functional SNPs were included in a genetic association analysis with specific cognitive domains, including memory, psychomotor speed, and information processing. Cross-sectional and longitudinal designs were used to explore genetic influences on baseline cognition at diagnosis and change from baseline over the first year since diagnosis, respectively. We found a statistically significant association between genotypic variation and memory function at both baseline (NRSF: rs1105434, rs2227902 and BDNF: rs1491850, rs2030324, rs11030094) and in our longitudinal analysis (NRSF: rs2227902 and BDNF: rs12273363). Psychomotor speed was also associated with genotype (NRSF rs3796529) in the longitudinal assessment. In line with our previous work on general cognitive function in the healthy aging population, we observed an additive interaction between risk alleles for the NRSF rs2227902 (G) and BDNF rs6265 (A) polymorphisms which was again consistent with a significantly greater decline in delayed recall over the first year since diagnosis. These findings support a role for the NRSF–BDNF pathway in the modulation of cognitive function in patients with newly diagnosed epilepsy., Highlights • Cognitive dysfunction is a common and important comorbidity in people with epilepsy. • Causes of cognitive problems are unknown, but genetics may be involved. • We compared NRSF and BDNF gene variants with cognition in new-onset epilepsy. • Deterioration in memory task scores from baseline was associated with genotype. • The NRSF/BDNF pathway may be relevant to cognitive function in people with epilepsy.