Changes in Muscle and Cerebral Deoxygenation and Perfusion during Repeated Sprints in Hypoxia to Exhaustion

During supramaximal exercise, exacerbated at exhaustion and in hypoxia, the circulatory system is challenged to facilitate oxygen delivery to working tissues through cerebral autoregulation which influences fatigue development and muscle performance. The aim of the study was to evaluate the effects of different levels of normobaric hypoxia on the changes in peripheral and cerebral oxygenation and performance during repeated sprints to exhaustion. Eleven recreationally active participants (six men and five women; 26.7 ± 4.2 years, 68.0 ± 14.0 kg, 172 ± 12 cm, 14.1 ± 4.7% body fat) completed three randomized testing visits in conditions of simulated altitude near sea-level (~380 m, FIO2 20.9%), ~2000 m (FIO2 16.5 ± 0.4%), and ~3800 m (FIO2 13.3 ± 0.4%). Each session began with a 12-min warm-up followed by two 10-s sprints and the repeated cycling sprint (10-s sprint: 20-s recovery) test to exhaustion. Measurements included power output, vastus lateralis, and prefrontal deoxygenation [near-infrared spectroscopy, delta (Δ) corresponds to the difference between maximal and minimal values], oxygen uptake, femoral artery blood flow (Doppler ultrasound), hemodynamic variables (transthoracic impedance), blood lactate concentration, and rating of perceived exertion. Performance (total work, kJ; -27.1 ± 25.8% at 2000 m, p < 0.01 and -49.4 ± 19.3% at 3800 m, p < 0.001) and pulse oxygen saturation (-7.5 ± 6.0%, p < 0.05 and -18.4 ± 5.3%, p < 0.001, respectively) decreased with hypoxia, when compared to 400 m. Muscle Δ hemoglobin difference ([Hbdiff]) and Δ tissue saturation index (TSI) were lower (p < 0.01) at 3800 m than at 2000 and 400 m, and lower Δ deoxyhemoglobin resulted at 3800 m compared with 2000 m. There were reduced changes in peripheral [Δ[Hbdiff], ΔTSI, Δ total hemoglobin ([tHb])] and greater changes in cerebral (Δ[Hbdiff], Δ[tHb]) oxygenation throughout the test to exhaustion (p < 0.05). Changes in cerebral deoxygenation were greater at 3800 m than at 2000 and 400 m (p < 0.01). This study confirms that performance in hypoxia is limited by continually decreasing oxygen saturation, even though exercise can be sustained despite maximal peripheral deoxygenation. There may be a cerebral autoregulation of increased perfusion accounting for the decreased arterial oxygen content and allowing for task continuation, as shown by the continued cerebral deoxygenation

Progress in tourism and destination wellbeing research

A proliferation of research in recent years has revealed a myriad of relationships between tourism and the concept of wellbeing. These include health benefits of visiting tourist destinations, a product focus on wellness and maintaining good health. Broader interpretations emphasize the complex ways in which tourism can influence the emotional, psychological, cognitive and spiritual dimensions of wellbeing, both for tourists and for destination communities. This study reflects an emerging paradigm shift that incorporates a deeper appreciation of the benefits derived at the destination level from a focus on health and wellbeing. The study highlights three key perspectives, namely the tourist, the destination community and the destination itself. The study concludes that research in this area is critical to the future development, management and marketing of sustainable and competitive destinations with the wellbeing of tourists, their destination host communities, and the overall destination experience, critical to their ultimate success

A set of codes for numerical convection and geodynamo calculations

We present a set of codes for calculating and displaying solutions to diverse problems within thermal convection and magnetic field generation in rotating fluid-filled spheres and spherical shells. There are diverse programs for the kinematic dynamo problem, the onset of thermal convection, and boundary-locked thermal convection, and time-stepping codes for non-magnetic convection and the dynamo with either homogeneous or spatially varying thermal boundary conditions. Where possible, all programs have been benchmarked against other codes and tested by reproducing previously published results. Each program comes with the complete source code, a pdf instruction manual, and at least one example run with a sample input file and all necessary files for describing an initial condition. The only prerequisite for running most of the codes is a FORTRAN compiler. The plotting programs require in addition the PGPLOT graphics library. All source code, examples, input files, solutions, and instructions are available for download from github and Zenodo

Oxygenation time course and neuromuscular fatigue during repeated cycling sprints with bilateral blood flow restriction.

The aim was to evaluate changes in peripheral and cerebral oxygenation, cardiorespiratory, and performance differences, as well as neuromuscular fatigue across multiple levels of blood flow restriction (BFR) during a repeated cycling sprint test to exhaustion (RST). Participants performed three RST (10-sec maximal sprints with 20-sec recovery until exhaustion) with measurements of power output and V̇O <sub>2peak</sub> as well as oxygenation (near-infrared spectroscopy) of the vastus lateralis and prefrontal cortex. Neuromuscular fatigue was assessed by femoral nerve stimulation to evoke the vastus lateralis. Tests were conducted with proximal lower limb bilateral vascular occlusion at 0%, 45%, and 60% of resting pulse elimination pressure. Total work decreased with BFR (52.5 ± 22.9% at 45%, 68.6 ± 32.6% at 60%, P < 0.01 compared with 0%) as V̇O <sub>2peak</sub> (12.6 ± 9.3% at 45%, 18.2 ± 7.2% at 60%, compared with 0%, P < 0.01). Decreased changes in muscle deoxyhemoglobin (∆[HHb]) during sprints were demonstrated at 60% compared to 0% (P < 0.001). Changes in total hemoglobin concentrations (∆[tHb]) increased at both 45% and 60% compared with 0% (P < 0.001). Cerebral ∆[tHb] increased toward exhaustion (P < 0.05). Maximal voluntary contraction (MVC), voluntary activation level (VAL), and root mean square (RMS)/M-wave ratio decreased at 60% compared with 0% (P < 0.001, all). MVC and VAL decreased between 45% and 60% (P < 0.05, both). The application of BFR during RST induced greater changes in tissue perfusion (via blood volume, ∆[tHb]) suggesting a possible stimulus for vascular blood flow regulation. Additionally, high-intensity sprint exercise with partial ischemia may challenge cerebral blood flow regulation and influence local fatigue development due to protection of cerebral function

BRG1 and BRM function antagonistically with c-MYC in adult cardiomyocytes to regulate conduction and contractility

Rationale The contractile dysfunction that underlies heart failure involves perturbations in multiple biological processes ranging from metabolism to electrophysiology. Yet the epigenetic mechanisms that are altered in this disease state have not been elucidated. SWI/SNF chromatin-remodeling complexes are plausible candidates based on mouse knockout studies demonstrating a combined requirement for the BRG1 and BRM catalytic subunits in adult cardiomyocytes. Brg1/Brm double mutants exhibit metabolic and mitochondrial defects and are not viable although their cause of death has not been ascertained. Objective To determine the cause of death of Brg1/Brm double-mutant mice, to test the hypothesis that BRG1 and BRM are required for cardiac contractility, and to identify relevant downstream target genes. Methods and results A tamoxifen-inducible gene-targeting strategy utilizing αMHC-Cre-ERT was implemented to delete both SWI/SNF catalytic subunits in adult cardiomyocytes. Brg1/Brm double-mutant mice were monitored by echocardiography and electrocardiography, and they underwent rapidly progressive ventricular dysfunction including conduction defects and arrhythmias that culminated in heart failure and death within 3 weeks. Mechanistically, BRG1/BRM repressed c-Myc expression, and enforced expression of a DOX-inducible c-MYC trangene in mouse cardiomyocytes phenocopied the ventricular conduction defects observed in Brg1/Brm double mutants. BRG1/BRM and c-MYC had opposite effects on the expression of cardiac conduction genes, and the directionality was consistent with their respective loss- and gain-of-function phenotypes. To support the clinical relevance of this mechanism, BRG1/BRM occupancy was diminished at the same target genes in human heart failure cases compared to controls, and this correlated with increased c-MYC expression and decreased CX43 and SCN5A expression. Conclusion BRG1/BRM and c-MYC have an antagonistic relationship regulating the expression of cardiac conduction genes that maintain contractility, which is reminiscent of their antagonistic roles as a tumor suppressor and oncogene in cancer

COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial

Propranolol is a nonselective β-adrenergic receptor antagonist that is efficacious in reducing facial pain. There is evidence that its analgesic efficacy might be modified by variants of the catechol-O-methyltransferase (COMT) gene. We tested the hypothesis in a subset of 143 non-Hispanic Whites from a randomized controlled trial of patients with painful temporomandibular disorder (TMD). Patients were genotyped for rs4680, a single nucleotide polymorphism of COMT, and randomly allocated to either propranolol 60 mg twice daily or placebo. During the 9-wk follow-up period, patients recorded daily ratings of facial pain intensity and duration; the product was computed as an index of facial pain. Postbaseline change in the index at week 9 (the primary endpoint) was analyzed as a continuous variable and dichotomized at thresholds of ≥30% and ≥50% reduction. Mixed models for repeated measures tested for the genotype × treatment group interaction and estimated means, odds ratios (ORs), and 95% confidence limits (95% CLs) of efficacy within COMT genotypes assuming an additive genetic model. In secondary analysis, the cumulative response curves were plotted for dichotomized reductions ranging from ≥20% to ≥70%, and genotype differences in area under the curve percentages (%AUC) were calculated to signify efficacy. Mean index reduction did not differ significantly (P = 0.277) according to genotype, whereas the dichotomized ≥30% reduction revealed greater efficacy among G:G homozygotes (OR = 10.9, 95%CL = 2.4, 50.7) than among A:A homozygotes (OR = 0.8, 95%CL = 0.2, 3.2) with statistically significant interaction (P = 0.035). Cumulative response curves confirmed greater (P = 0.003) efficacy for G:G homozygotes (%AUC difference = 43.7, 95%CL = 15.4, 72.1) than for A:A homozygotes (%AUC difference = 6.5, 95%CL = -30.2, 43.2). The observed antagonistic effect of the A allele on propranolol’s efficacy was opposite the synergistic effect hypothesized a priori. This unexpected result highlights the need for better knowledge of COMT’s role in pain pathogenesis if the gene is to be used for precision-medicine treatment of TMD (ClinicalTrials.gov NCT02437383)

Young people's uses of celebrity: Class, gender and 'improper' celebrity

This is an Author's Accepted Manuscript of an article published in Discourse: Studies in the Cultural Politics of Education, 34(1), 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/01596306.2012.698865.In this article, we explore the question of how celebrity operates in young people's everyday lives, thus contributing to the urgent need to address celebrity's social function. Drawing on data from three studies in England on young people's perspectives on their educational and work futures, we show how celebrity operates as a classed and gendered discursive device within young people's identity work. We illustrate how young people draw upon class and gender distinctions that circulate within celebrity discourses (proper/improper, deserving/undeserving, talented/talentless and respectable/tacky) as they construct their own identities in relation to notions of work, aspiration and achievement. We argue that these distinctions operate as part of neoliberal demands to produce oneself as a ‘subject of value’. However, some participants produced readings that show ambivalence and even resistance to these dominant discourses. Young people's responses to celebrity are shown to relate to their own class and gender position.The Arts and Humanities Research Council, the British Academy, the Economic and Social Research Council, and the UK Resource Centre for Women in Science Engineering and Technology

A survey of partial differential equations in geometric design

YesComputer aided geometric design is an area where the improvement of surface generation techniques is an everlasting demand since faster and more accurate geometric models are required. Traditional methods for generating surfaces were initially mainly based upon interpolation algorithms. Recently, partial differential equations (PDE) were introduced as a valuable tool for geometric modelling since they offer a number of features from which these areas can benefit. This work summarises the uses given to PDE surfaces as a surface generation technique togethe

FOREWARNS: development and multifaceted verification of enhanced regional-scale surface water flood forecasts

Surface water flooding (SWF) is a severe hazard associated with extreme convective rainfall, whose spatial and temporal sparsity belie the significant impacts it has on populations and infrastructure. Forecasting the intense convective rainfall that causes most SWF on the temporal and spatial scales required for effective flood forecasting remains extremely challenging. National-scale flood forecasts are currently issued for the UK and are well regarded amongst flood responders, but there is a need for complementary enhanced regional information. Here we present a novel SWF-forecasting method, FOREWARNS (Flood fOREcasts for Surface WAter at a RegioNal Scale), that aims to fill this gap in forecast provision. FOREWARNS compares reasonable worst-case rainfall from a neighbourhood-processed, convection-permitting ensemble forecast system against pre-simulated flood scenarios, issuing a categorical forecast of SWF severity. We report findings from a workshop structured around three historical flood events in Northern England, in which forecast users indicated they found the forecasts helpful and would use FOREWARNS to complement national guidance for action planning in advance of anticipated events. We also present results from objective verification of forecasts for 82 recorded flood events in Northern England from 2013–2022, as well as 725 daily forecasts spanning 2019–2022, using a combination of flood records and precipitation proxies. We demonstrate that FOREWARNS offers good skill in forecasting SWF risk, with high spatial hit rates and low temporal false alarm rates, confirming that user confidence is justified and that FOREWARNS would be suitable for meeting the user requirements of an enhanced operational forecast