Genetic heterogeneity of motor neuropathies.

OBJECTIVE: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. METHODS: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). RESULTS: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62-2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. CONCLUSIONS: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies

Lack of Impacts during Early Establishment Highlights a Short-Term Management Window for Minimizing Invasions from Perennial Biomass Crops

Managing intentional species introductions requires evaluating potential ecological risks. However, it is difficult to weigh costs and benefits when data about interactions between novel species and the communities they are introduced to are scarce. In anticipation of expanded cultivation of perennial biomass crops, we experimentally introduced Miscanthus sinensis and Miscanthus × giganteus (two non-native candidate biomass crops) into two different non-crop habitats (old field and flood-plain forest) to evaluate their establishment success and impact on ambient local communities. We followed these controlled introductions and the composition dynamics of the receiving communities over a 5-year period. Habitats differed widely in adult Miscanthus survival and reproduction potential between species, although seed persistence and seedling emergence were similar in the two biomass crops in both habitats. Few introductions survived in the floodplain forest habitat, and this mortality precluded analyses of their potential impacts there. In old field habitats, proportional survival ranged from 0.3 to 0.4, and plant survival and growth increased with age. However, there was no evidence of biomass crop species effects on community richness or evenness or strong impacts on the resident old field constituents across 5 years. These results suggest that Miscanthus species could establish outside of cultivated fields, but there will likely be a lag in any impacts on the receiving communities. Local North American invasions by M. sinensis and M. sacchariflorus display the potential for Miscanthus species to develop aggressively expanding populations. However, the weak short-term community-level impacts demonstrated in the current study indicate a clear management window in which eradicating species footholds is easily achieved, if they can be detected early enough. Diligent long-term monitoring, detection, and eradication plans are needed to successfully minimize harmful invasions from these biomass crops

Growth-Based Bacterial Viability Assay for Interference-Free and High-Throughput Toxicity Screening of Nanomaterials

Current high-throughput approaches evaluating toxicity of chemical agents toward bacteria typically rely on optical assays, such as luminescence and absorbance, to probe the viability of the bacteria. However, when applied to toxicity induced by nanomaterials, scattering and absorbance from the nanomaterials act as interferences that complicate quantitative analysis. Herein, we describe a bacterial viability assay that is free of optical interference from nanomaterials and can be performed in a high-throughput format on 96-well plates. In this assay, bacteria were exposed to various materials and then diluted by a large factor into fresh growth medium. The large dilution ensured minimal optical interference from the nanomaterial when reading optical density, and the residue left from the exposure mixture after dilution was confirmed not to impact the bacterial growth profile. The fractions of viable cells after exposure were allowed to grow in fresh medium to generate measurable growth curves. Bacterial viability was then quantitatively correlated to the delay of bacterial growth compared to a reference regarded as 100% viable cells; data analysis was inspired by that in quantitative polymerase chain reactions, where the delay in the amplification curve is correlated to the starting amount of the template nucleic acid. Fast and robust data analysis was achieved by developing computer algorithms carried out using R. This method was tested on four bacterial strains, including both Gram-negative and Gram-positive bacteria, showing great potential for application to all culturable bacterial strains. With the increasing diversity of engineered nanomaterials being considered for large-scale use, this high-throughput screening method will facilitate rapid screening of nanomaterial toxicity and thus inform the risk assessment of nanoparticles in a timely fashion

Producing success: a critical analysis of athlete development governance in six countries

This paper aims to analyse and compare athlete development governance in Australia, Finland, Germany, New Zealand, Sweden and Switzerland. We adopt a Foucauldian framework to theorise athlete development governance as shaped by and based on distinct ‘government mentalities’ and ‘modes of governance’. Qualitative procedures were used to collect and analyse 58 documents related to the 6 countries’ athlete development governance and to conduct 14 informal interviews with national elite sport system experts. Our results confirm other scholars’ findings that sport governance is moving towards managerialist government mentalities. Specific modes of governance that are being implemented to systematise athlete development include targeted forms of funding and the modelling of athlete development. However, the results also highlight how athlete development governance is a site of negotiation, arising from (a) historical events, (b) sociopolitical contexts, (c) financial conditions, (d) government mentalities and (e) sport science knowledge. Our examination demonstrates how these factors not only problematise athlete development governance but also allow for distinctive local athlete development government discursivities and/or sport-specific adjustments such as less result-driven and more holistic interpretations of athlete development. We conclude by outlining implications intended to support stakeholders’ (e.g. coaches’, sport directors’) engagement in conceptualising, implementing and/or revising athlete development frameworks

Sedation and analgesia for reduction of pediatric ileocolic intussusception

Importance : Ileocolic intussusception is an important cause of intestinal obstruction in children. Reduction of ileocolic intussusception using air or fluid enema is the standard of care. This likely distressing procedure is usually performed without sedation or analgesia, but practice variation exists. Objective : To characterize the prevalence of opioid analgesia and sedation and assess their association with intestinal perforation and failed reduction. Design, Setting, and Participants : This cross-sectional study reviewed medical records of children aged 4 to 48 months with attempted reduction of ileocolic intussusception at 86 pediatric tertiary care institutions in 14 countries from January 2017 to December 2019. Of 3555 eligible medical records, 352 were excluded, and 3203 medical records were eligible. Data were analyzed in August 2022. Exposures : Reduction of ileocolic intussusception. Main outcomes and measures : The primary outcomes were opioid analgesia within 120 minutes of reduction based on the therapeutic window of IV morphine and sedation immediately before reduction of intussusception. Results : We included 3203 patients (median [IQR] age, 17 [9-27] months; 2054 of 3203 [64.1%] males). Opioid use was documented in 395 of 3134 patients (12.6%), sedation 334 of 3161 patients (10.6%), and opioids plus sedation in 178 of 3134 patients (5.7%). Perforation was uncommon and occurred in 13 of 3203 patients (0.4%). In the unadjusted analysis, opioids plus sedation (odds ratio [OR], 5.92; 95% CI, 1.28-27.42; P = .02) and a greater number of reduction attempts (OR, 1.48; 95% CI, 1.03-2.11; P = .03) were significantly associated with perforation. In the adjusted analysis, neither of these covariates remained significant. Reductions were successful in 2700 of 3184 attempts (84.8%). In the unadjusted analysis, younger age, no pain assessment at triage, opioids, longer duration of symptoms, hydrostatic enema, and gastrointestinal anomaly were significantly associated with failed reduction. In the adjusted analysis, only younger age (OR, 1.05 per month; 95% CI, 1.03-1.06 per month; P < .001), shorter duration of symptoms (OR, 0.96 per hour; 95% CI, 0.94-0.99 per hour; P = .002), and gastrointestinal anomaly (OR, 6.50; 95% CI, 2.04-20.64; P = .002) remained significant. Conclusions and Relevance : This cross-sectional study of pediatric ileocolic intussusception found that more than two-thirds of patients received neither analgesia nor sedation. Neither was associated with intestinal perforation or failed reduction, challenging the widespread practice of withholding analgesia and sedation for reduction of ileocolic intussusception in children