White matter abnormalities in active elite adult rugby players

The recognition, diagnosis and management of mild traumatic brain injuries is difficult and confusing. It is unclear how the severity and number of injuries sustained relate to brain injuries such as diffuse axonal injury, diffuse vascular injury and progressive neurodegeneration. Advances in neuroimaging techniques enable the investigation of neuropathologies associated with acute and long-term effects of injury. Head injuries are the most commonly reported injury seen during professional rugby. There is increased vigilance for the immediate effects of these injuries in matches, but there has been surprisingly little research investigating the longer-term effects of rugby participation. Here we present a longitudinal observational study investigating the relationship of exposure to rugby participation and sub-acute head injuries in professional adult male and female rugby union and league players using advanced MRI. Diffusion tensor imaging and susceptibility weighted imaging was used to assess white matter structure and evidence of axonal and diffuse vascular injury. We also studied changes in brain structure over time using Jacobian Determinant statistics extracted from serial volumetric imaging. We tested 41 male and 3 female adult elite rugby players, of whom 21 attended study visits after a head injury, alongside 32 non-sporting controls, 15 non-collision-sport athletic controls and 16 longitudinally assessed controls. 18 rugby players participated in the longitudinal arm of the study, with a second visit at least 6 months after their first scan. Neuroimaging evidence of either axonal injury or diffuse vascular injury was present in 23% (10/44) of players. In the non-acutely injured group of rugby players, abnormalities of fractional anisotropy and other diffusion measures were seen. In contrast, non-collision-sport athletic controls were not classified as showing abnormalities. A group level contrast also showed evidence of sub-acute injury using diffusion tensor imaging in rugby players. Examination of longitudinal imaging revealed unexpected reductions in white matter volume in the elite rugby players studied. These changes were not related to self-reported head injury history or neuropsychological test scores and might indicate excess neurodegeneration in white matter tracts affected by injury. Taken together, our findings suggest an association of participation in elite adult rugby with changes in brain structure. Further well-designed large scale studies are needed to understand the impact of both repeated sports related head impacts and head injuries on brain structure, and to clarify whether the abnormalities we have observed are related to an increased risk of neurodegenerative disease and impaired neurocognitive function following elite rugby participation

White matter abnormalities in active elite adult rugby players

The recognition, diagnosis and management of mild traumatic brain injuries are difficult and confusing. It is unclear how the severity and number of injuries sustained relate to brain injuries, such as diffuse axonal injury, diffuse vascular injury and progressive neurodegeneration. Advances in neuroimaging techniques enable the investigation of neuropathologies associated with acute and long-term effects of injury. Head injuries are the most commonly reported injury seen during professional rugby. There is increased vigilance for the immediate effects of these injuries in matches, but there has been surprisingly little research investigating the longer-term effects of rugby participation. Here, we present a longitudinal observational study investigating the relationship of exposure to rugby participation and sub-acute head injuries in professional adult male and female rugby union and league players using advanced MRI. Diffusion tensor imaging and susceptibility weighted imaging was used to assess white matter structure and evidence of axonal and diffuse vascular injury. We also studied changes in brain structure over time using Jacobian Determinant statistics extracted from serial volumetric imaging. We tested 41 male and 3 female adult elite rugby players, of whom 21 attended study visits after a head injury, alongside 32 non-sporting controls, 15 non-collision-sport athletic controls and 16 longitudinally assessed controls. Eighteen rugby players participated in the longitudinal arm of the study, with a second visit at least 6 months after their first scan. Neuroimaging evidence of either axonal injury or diffuse vascular injury was present in 23% (10/44) of players. In the non-acutely injured group of rugby players, abnormalities of fractional anisotropy and other diffusion measures were seen. In contrast, non-collision-sport athletic controls were not classified as showing abnormalities. A group level contrast also showed evidence of sub-acute injury using diffusion tensor imaging in rugby players. Examination of longitudinal imaging revealed unexpected reductions in white matter volume in the elite rugby players studied. These changes were not related to self-reported head injury history or neuropsychological test scores and might indicate excess neurodegeneration in white matter tracts affected by injury. Taken together, our findings suggest an association of participation in elite adult rugby with changes in brain structure. Further well-designed large-scale studies are needed to understand the impact of both repeated sports-related head impacts and head injuries on brain structure, and to clarify whether the abnormalities we have observed are related to an increased risk of neurodegenerative disease and impaired neurocognitive function following elite rugby participation

The theory of international business: the role of economic models

This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

Lung volume reduction eligibility in patients with COPD completing pulmonary rehabilitation: results from the UK National Asthma and COPD Audit Programme

Copyright © Author(s) (or their employer(s)) 2020. Objectives: To establish what proportion of patients completing a UK pulmonary rehabilitation (PR) programme meet the 2018 National Institute for Health and Care Excellence (NICE) chronic obstructive pulmonary disease (COPD) guideline (NG115) criteria to have a respiratory review to establish whether referral to a lung volume reduction multidisciplinary team would be appropriate. This respiratory review would include evaluation of the presence of hyperinflation and the presence of emphysema on CT scan. The NICE criteria include measures of breathlessness and exercise capacity but these parameters are not completely defined. Design Observational study. Setting PR programmes across the UK in 2015 (210 centres) and 2017 (184 centres) entering data into the Royal College of Physicians’ National Asthma and COPD Audit Programme. Participants: 8295 (55.7%) of 14 889 patients in programmes using incremental shuttle walk test (ISWT) or 6-minute walk test (6MWT) as an outcome measure completed PR, and 4856 (32.6%) had complete data recorded (6MWT/ISWT, baseline spirometry, Medical Research Council (MRC) dyspnoea score). Results: Depending on the walking test safety threshold adopted for the ISWT (≥140 m or ≥ 80 m) and the MRC dyspnoea score threshold used (MRC score ≥3 or ≥4 at the end of PR), between 4.9% and 18.1% of PR completers met the NICE criteria for a lung volume reduction-focused respiratory review. Conclusions: Lung volume reduction therapies are beneficial in appropriately selected patients with COPD, but few procedures are performed, and treatment pathways are unclear. These data help to inform the feasibility of the approach recommended by NICE and highlight the need for future systematic pathways to reduce inequalities in patients being considered for effective treatments.National Institute for Health Research, through the Research for Patient Benefit scheme (PB-PG-1014-35051)

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Robust estimation of microbial diversity in theory and in practice

Quantifying diversity is of central importance for the study of structure, function and evolution of microbial communities. The estimation of microbial diversity has received renewed attention with the advent of large-scale metagenomic studies. Here, we consider what the diversity observed in a sample tells us about the diversity of the community being sampled. First, we argue that one cannot reliably estimate the absolute and relative number of microbial species present in a community without making unsupported assumptions about species abundance distributions. The reason for this is that sample data do not contain information about the number of rare species in the tail of species abundance distributions. We illustrate the difficulty in comparing species richness estimates by applying Chao's estimator of species richness to a set of in silico communities: they are ranked incorrectly in the presence of large numbers of rare species. Next, we extend our analysis to a general family of diversity metrics ("Hill diversities"), and construct lower and upper estimates of diversity values consistent with the sample data. The theory generalizes Chao's estimator, which we retrieve as the lower estimate of species richness. We show that Shannon and Simpson diversity can be robustly estimated for the in silico communities. We analyze nine metagenomic data sets from a wide range of environments, and show that our findings are relevant for empirically-sampled communities. Hence, we recommend the use of Shannon and Simpson diversity rather than species richness in efforts to quantify and compare microbial diversity.Comment: To be published in The ISME Journal. Main text: 16 pages, 5 figures. Supplement: 16 pages, 4 figure

Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells

BACKGROUND: Lung fluid balance in the healthy lung is dependent upon finely regulated vectorial transport of ions across the alveolar epithelium. Classically, the cellular locus of the major ion transport processes has been widely accepted to be the alveolar type II cell. Although evidence is now emerging to suggest that the alveolar type I cell might significantly contribute to the overall ion and fluid homeostasis of the lung, direct assessment of functional ion channels in type I cells has remained elusive. METHODS: Here we describe a development of a lung slice preparation that has allowed positive identification of alveolar type I cells within an intact and viable alveolar epithelium using living cell immunohistochemistry. RESULTS: This technique has allowed, for the first time, single ion channels of identified alveolar type I cells to be recorded using the cell-attached configuration of the patch-clamp technique. CONCLUSION: This exciting new development should facilitate the ascription of function to alveolar type I cells and allow us to integrate this cell type into the general model of alveolar ion and fluid balance in health and disease

Worry is associated with robust reductions in heart rate variability: a transdiagnostic study of anxiety psychopathology

Background Individuals with anxiety disorders display reduced resting-state heart rate variability (HRV), although findings have been contradictory and the role of specific symptoms has been less clear. It is possible that HRV reductions may transcend diagnostic categories, consistent with dimensional-trait models of psychopathology. Here we investigated whether anxiety disorders or symptoms of anxiety, stress, worry and depression are more strongly associated with resting-state HRV. Methods Resting-state HRV was calculated in participants with clinical anxiety (n = 25) and healthy controls (n = 58). Symptom severity measures of worry, anxiety, stress, and depression were also collected from participants, regardless of diagnosis. Results Participants who fulfilled DSM-IV criteria for an anxiety disorder displayed diminished HRV, a difference at trend level significance (p = .1, Hedges’ g = -.37, BF10 = .84). High worriers (Total n = 41; n = 22 diagnosed with an anxiety disorder and n = 19 not meeting criteria for any psychopathology) displayed a robust reduction in resting state HRV relative to low worriers (p = .001, Hedges’ g = -.75, BF10 = 28.16). Conclusions The specific symptom of worry – not the diagnosis of an anxiety disorder – was associated with the most robust reductions in HRV, indicating that HRV may provide a transdiagnostic biomarker of worry. These results enhance understanding of the relationship between the cardiac autonomic nervous system and anxiety psychopathology, providing support for dimensional-trait models consistent with the Research Domain Criteria framework

Sodium bicarbonate ingestion and individual variability in time to peak pH

The aim of this study was to determine the individual variability in time to peak pH after the consumption of a 300mg.kg-1 dose of sodium bicarbonate (NaHCO3). Seventeen active males volunteered to participate in the study (mean ± SD: age 21.38 ± 1.5y; mass 75.8 ± 5.8kg; height 176.8 ± 7.6cm). Participants reported to the laboratory where a resting capillary blood sample was taken aseptically from the fingertip. After this, 300 mg.kg-1 of NaHCO3 in 400ml of water with 50ml of flavoured cordial was ingested. Participants then rested for 90 min during which repeated blood samples were procured at 10 minute intervals for 60 mins and then every 5 min until 90 min. Blood pH concentrations were measured using a blood gas analyser. Results suggested that time to peak pH (64.41±18.78 min) was highly variable with a range of 10-85 min and a coefficient of variation of 29.16%. A bi-modal distribution occurred, at 65 and 75 min. In conclusion, researchers and athletes, when using NaHCO3 as an ergogenic aid, should determine, in advance their time to peak pH to best utilise the added buffering capacity this substance allows