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\"Leisure studies encompasses the broadest range of leisure and sports pursuits and marries management, administration and sports, as well as customer service. Key Concepts in Leisure presents an indispensable guide to the key themes and concepts in this rapidly developing, fast-paced and demanding industry\"--Provided by publisher.

The migration of male international soccer student-athletes to American collegiate institutions has seen an ascending trend of participation popularity. Using a phenomenological research design, I sought to gain an in-depth understanding of how male international soccer student-athletes experienced their recruitment processes with National Collegiate Athletic Association (NCAA) Division I institutions. Seventeen participants from various universities engaged with me in semi-structured in-depth interview conversations. Analysis of the information they shared, suggested five significant themes rooted in the communicative nature of the recruitment process: 1) Social Acceptance, 2) Sense of Belonging, 3) Acceptance vs Rejection, 4) The Incognizant Reality, and 5) Increase of Self-Awareness. These themes, which resonate with social identity theory, have the potential to offer beneficial information to institutions, coaches, recruiters and prospective international student athletes as well as to provide a qualitative framework from which future studies can be modeled.

Introduction: Rapid-onset obesity, hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) is a rare syndrome beginning at 3-6 years of age with approximately 150 cases described. Additional features include eye abnormalities, neurobehavioral dysfunction and paraneoplastic tumors. The etiology of the complex phenotype remains unknown. Methods: This study aims to investigate the genetic landscape of this complex phenotype by whole exome sequencing (WES) and copy number variation (CNV) analysis. We recruited 33 families (27 trios, 1 duo and 5 singletons) with a proband with ROHHAD syndrome (Ize-Ludlow 2007, Pediatrics). WES of 89 individuals was performed at the Center for Mendelian Genomics, Broad Institute. The Illumina platform with a mean coverage of ~100X (> 90% targets 20x) and Infinium Global Screening Array BeadChip 24v1.0 were used. Results: This report includes 28 probands (female = 18, 64%) with rapid onset obesity (100%), hypoventilation (88%), hypothalamic dysfunction (69%), eye disorders (62%) and neurobehavioral abnormalities (76%). Neuroendocrine tumor, ganglioneuroblastoma, was present in 38% (n=13). No unifying causative single gene or CNV was identified, but a number of sequence variants are prioritized. ARNT2, which encodes for a helix-loop-helix transcription factor, plays a role in the development of the hypothalamic-pituitary axis, postnatal brain growth, and visual and renal function. The de novo monoallelic missense variant was found in a 14-year old white girl (BMIz +3.25) with extreme obesity and a neurobehavioral phenotype. OCRL1, a multi-domain protein involved in cytoskeleton-plasma membrane adhesion, endosomal trafficking and in primary cilium assembly. Mutations in this gene have also been known to cause Lowe syndrome. A hemizygous X-linked frameshift variant in a 5-year old white boy with extreme obesity (BMIz +5.48), central hypoventilation neurobehavioral dysfunction and ganglioneuroblastoma. A monoallelic missense variant in NSD1, a transcriptional intermediary factor acting as a histone methyltransferase, was identified in a 8-year old Hispanic girl with severe obesity (BMIz +2.91), neurobehavioral disorder, pituitary and eye dysfunction and ganglioneuroblastoma. NSD1 is known to cause Sotos and Beckwith-Wiedemann. Compound heterozygous variants in KIF7, a key component of the Hedgehog signaling pathway, were identified in a 14-year old white girl with severe obesity (BMIz +3.00), autistic behavior, pituitary dysfunction and central hypoventilation. This gene is known to cause autosomal recessive hydrolethalis and acroscallosal syndromes with mutations also noted in Bardet-Biedl, Meckel and Joubert syndromes. Conclusion: While no unifying genetic cause has been identified in ROHHAD syndrome, it is possible that the phenotype represents a collection of complex genetic syndromes.

DR ALLEN Purcival's defence of the Hongkong Singers' recent production of Johann Strauss' Die Fledermaus was certainly encour-...

JONATHAN SUTHERLAND and DIANE CANWELL, Zulu Kings and Their Armies. Barnsley: Pen & Sword Military (hb £19.99 - 1 84415 060 7). 2004, 198 pp.

Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count. We did this randomised, double-blind, placebo-controlled, parallel-group, pivotal phase 2b clinical trial at 174 study sites across 16 countries or regions. Adults (aged ≥18 years) with an asthma diagnosis for 12 months or more based on the Global Initiative for Asthma 2009 Guidelines receiving treatment with medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist were eligible for participation. Patients were randomly assigned (1:1:1:1:1) to receive subcutaneous dupilumab 200 mg or 300 mg every 2 weeks or every 4 weeks, or placebo, over a 24-week period. The primary endpoint was change from baseline at week 12 in forced expiratory volume in 1 s (FEV1 in L) in patients with baseline blood eosinophil counts of at least 300 eosinophils per μL assessed in the intention-to-treat population. Safety outcomes were assessed in all patients that received at least one dose or part of a dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT01854047, and with the EU Clinical Trials Register, EudraCT number 2013-000856-16. 769 patients (158 in the placebo group and 611 in the dupilumab groups) received at least one dose of study drug. In the subgroup with at least 300 eosinophils per μL, the greatest increases (200 mg every 2 weeks, p=0·0008; 300 mg every 2 weeks, p=0·0063) in FEV1 compared with placebo were observed at week 12 with doses every 2 weeks in the 300 mg group (mean change 0·39 L [SE 0·05]; mean difference 0·21 [95% CI 0·06–0·36; p=0·0063]) and in the 200 mg group (mean change 0·43 L [SE 0·05]; mean difference 0·26 [0·11–0·40; p=0·0008]) compared with placebo (0·18 L [SE 0·05]). Similar significant increases were observed in the overall population and in the fewer than 300 eosinophils per μL subgroup (overall population: 200 mg every 2 weeks, p<0·0001; 300 mg every 2 weeks, p<0·0001; <300 eosinophils per μL: 200 mg every 2 weeks, p=0·0034; 300 mg every 2 weeks, p=0·0086), and were maintained to week 24. Likewise, dupilumab every 2 weeks produced the greatest reductions in annualised rates of exacerbation in the overall population (70–70·5%), the subgroup with at least 300 eosinophils per μL (71·2–80·7%), and the subgroup with fewer than 300 eosinophils per μL (59·9–67·6%). The most common adverse events with dupilumab compared with placebo were upper respiratory tract infections (33–41% vs 35%) and injection-site reactions (13–26% vs 13%). Dupilumab increased lung function and reduced severe exacerbations in patients with uncontrolled persistent asthma irrespective of baseline eosinophil count and had a favourable safety profile, and hence in addition to inhaled corticosteroids plus long-acting β2-agonist therapy could improve the lives of patients with uncontrolled persistent asthma compared with standard therapy alone. Sanofi-Genzyme and Regeneron Pharmaceuticals.

Islet transplantation is an evolving therapy that may be considered for patients with type 1 diabetes mellitus complicated by severe hypoglycemia or labile diabetes, provided all other attempts to stabilize glycemic control have been exhausted. This multicenter trial confirms that islet transplantation using the Edmonton protocol can successfully restore long-term endogenous production of insulin and glycemic stability in such patients, but insulin independence is usually not sustainable. Islet transplantation using the Edmonton protocol can successfully restore long-term endogenous production of insulin and glycemic stability in such patients, but insulin independence is usually not sustainable. Despite substantial improvements in insulin therapy and the care of patients with type 1 diabetes mellitus, a subgroup of patients is disabled by refractory hypoglycemia. Cell-based therapy with islet transplantation offers the possibility of improved glycemic control. The past three decades have witnessed substantial progress in islet transplantation. 1 – 3 Before the year 2000, few centers performing islet transplantation achieved high rates of sustainable insulin independence after this procedure among patients with type 1 diabetes mellitus. 1 – 3 In 2000, Shapiro et al. 4 reported their initial findings with up to a year of follow-up in seven consecutive subjects treated with glucocorticoid-free immunosuppressive . . .

Plasmodium ovale curtisi ( Poc) and Plasmodium ovale wallikeri ( Pow ) are relapsing malaria parasites endemic to Africa and Asia that were previously thought to represent a single species. Amid increasing detection of ovale malaria in sub-Saharan Africa, we present a population genomic study of both species across the continent. We conducted whole-genome sequencing of 25 isolates from Central and East Africa and analyzed them alongside 20 previously published African genomes. Isolates are predominantly monoclonal (43/45), with their genetic similarity aligning with geography. Pow shows lower average nucleotide diversity (1.8×10 −4 ) across the genome compared to Poc (3.0×10 −4 ) (p < 0.0001). Signatures of selective sweeps involving the dihydrofolate reductase gene have been found in both species, as are signs of balancing selection at the merozoite surface protein 1 gene. Differences in the nucleotide diversity of Poc and Pow may reflect unique demographic history, even as similar selective forces facilitate their resilience to malaria control interventions. Genomic analyses, performed by Carey-Ewend et al., reveal that Plasmodium ovale curtisi and wallikeri in sub-Saharan Africa show similar low complexity of infection, relatedness by geography, and signatures of selection. However, P. ovale wallikeri harbors lower nucleotide diversity.

Breast cancer in Ghana is a growing public health problem with increasing incidence and poor outcomes. Lack of access to comprehensive treatment in Ghana may be a contributing factor to its high mortality. The purpose of this study was to evaluate the availability of treatments nationwide and systematically identify high yield areas for targeted expansion. We conducted a cross-sectional, nationwide hospital-based survey from November 2020-October 2021. Surveys were conducted in person with trained research assistants and described hospital availability of all breast cancer treatments and personnel. All individual treatment services were reported, and hospitals were further stratified into levels of multi-modal treatment modeled after the National Comprehensive Cancer Network (NCCN) Framework treatment recommendations for low-resource settings. Level 3 included Tamoxifen and surgery (mastectomy with axillary lymph node sampling); Level 2 included Level 3 plus radiation, aromatase inhibitors, lumpectomy, and sentinel lymph node biopsy; Level 1 included Level 2 plus Her2 therapy and breast reconstruction. Hospitals were identified that could expand to these service levels based on existing services, location and personnel. The distance of the total population from treatment services before and after hypothetical expansion was determined with a geospatial analysis. Of the 328 participating hospitals (95% response rate), 9 hospitals had Level 3 care, 0 had Level 2, and 2 had Level 1. Twelve hospitals could expand to Level 3, 1 could expand to Level 2, and 1 could expand to Level 1. With expansion, the population percentage within 75km of Level 1, 2 and 3 care would increase from 42% to 50%, 0 to 6% and 44% to 67%, respectively. Multi-modal breast cancer treatment is available in Ghana, but it is not accessible to most of the population. Leveraging the knowledge of current resources and population proximity provides an opportunity to identify high-yield areas for targeted expansion.