Fostering a Learning Environment: Coaches and the Motivational Climate

To foster athletes' learning and to continue to learn as a coach, it is useful to reflect on the motivational climate developed through the coaching process. The purpose of this paper is to provide a synthesis of research concerning the motivational climate fostered by coaches that extends existing notions of the motivational climate beyond competence-focused goals to include other athlete needs such as autonomy and relatedness. The paper brings together quantitative and qualitative research on coaching and examines both athletes' and coaches' perspectives relating to the motivational climate. Conceptualisations of the climate created by coaches have traditionally emphasised competence, but quality coaches also understand, support, and care for athletes as people. In doing so, they can foster athletes' sense of autonomy and relatedness. Satisfaction of these needs has been associated with an environment conducive to learning and research demonstrates that coaches' practices are associated with the extent to which these needs are satisfied. The challenges and implications of this for coaches and researchers are discussed

New Zealand athletes' attitudes towards seeking sport psychology consultation

The aim of this study was to use the Sport Psychology Attitudes-Revised (SPA-R) questionnaire (Martin, Kellman, Lavallee & Page, 2002) to develop an understanding of the attitudes elite New Zealand athletes (N = 112) hold towards sport psychology so that services can be tailored to accommodate these views. The influence of athlete characteristics such as nationality, gender, age, level of competition achieved, and previous use of sport psychology on attitudes was explored. Further, the SPA-R was used as a measure of attitudes within the Theory of Reasoned Action (TRA; Ajzen & Fishbein, 1980) and Theory Planned Behaviour (TPB; Ajzen, 1985, 1991), and integrated with measures of subjective norm and perceived behavioural control to investigate the influence of these variables on predicting athletes' intention to use sport psychology. Results suggested that New Zealand athletes generally held positive attitudes regarding sport psychology, with gender and previous experience of sport psychology significantly influencing attitudes. Regression analyses indicated that the TPB was a better model than the TRA for predicting intention, and the variables predicted 39.7% of variance in intention to use sport psychology. The only SPA-R subscale that contributed significantly was confidence in sport psychology, and perceived behavioural control and subjective norm also contributed significantly. These findings suggest the SPA-R may have limited value in predicting intentions, although the TPB could provide a useful theoretical framework to direct interventions aimed at increasing athletes' intention to use sport psychology

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

A Radio-to-mm Census of Star-forming Galaxies in Protocluster 4C23.56 at Z = 2.5:Gas Mass and Its Fraction Revealed with ALMA

We investigate gas contents of star-forming galaxies associated with protocluster 4C23.56 at z = 2.49 by using the redshifted CO (3-2) and 1.1 mm dust continuum with the Atacama Large Millimeter/submillimeter Array. The observations unveil seven CO detections out of 22 targeted Hα emitters (HAEs) and four out of 19 in 1.1 mm dust continuum. They have high stellar mass ({M}\star > 4× {10}10 M ⊙) and exhibit a specific star-formation rate typical of main-sequence star-forming galaxies at z˜ 2.5. Different gas-mass estimators from CO (3-2) and 1.1 mm yield consistent values for simultaneous detections. The gas mass ({M}{gas}) and gas fraction ({f}{gas}) are comparable to those of field galaxies, with {M}{gas}=[0.3,1.8]× {10}11× ({α }{CO}/(4.36× A(Z))) {M}⊙ , where {α }{CO} is the CO-to-H2 conversion factor and A(Z) is the additional correction factor for the metallicity dependence of {α }{CO}, and < {f}{gas}> =0.53+/- 0.07 from CO (3-2). Our measurements place a constraint on the cosmic gas density of high-z protoclusters, indicating that the protocluster is characterized by a gas density higher than that of the general fields by an order of magnitude. We found ρ ({H}2)˜ 5× {10}9 {M}⊙ {{Mpc}}-3 with the CO(3-2) detections. The five ALMA CO detections occur in the region of highest galaxy surface density, where the density positively correlates with global star-forming efficiency (SFE) and stellar mass. Such correlations possibly indicate a critical role of the environment on early galaxy evolution at high-z protoclusters, though future observations are necessary for confirmation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Motivation in Masters sport: Achievement and social goals

Objective - This study examined the collective relationships amongst achievement goals, social goals and motivational correlates in Masters sport. Method - The participants were 373 (184 females; 189 males) Masters athletes from six sports. Ages ranged from 29 years to 77 years (mean=48 years). Cluster analysis was employed to identify 'goal profiles' of two achievement goals (task and ego) and three social goals (affiliation, recognition, status). MANOVA was employed to examine the goal profiles for differences on self-perceptions, affect, and motivation. Results - Five goal profiles were identified and labeled as follows: Cluster 1 (Lo-Aff) low affiliation, moderate task, ego, status, and recognition; Cluster 2 (Lo-Val) low ego, status, and recognition, moderate task and affiliation; Cluster 3 (Hi-Social) high affiliation and status, moderate recognition and task, and low ego; Cluster 4 (Lo-Ach) low task and ego, moderate affiliation, status, and recognition; and Cluster 5 (Hi-Ach) high task, ego, and recognition, moderate affiliation and status. MANOVA revealed that Cluster 3 (Hi-Social) was highest on enjoyment and perceived belonging, while Clusters 3 and 5 (Hi-Ach) were highest on intrinsic motivation, commitment, and perceived ability. Clusters 1 (Lo-Aff) and 4 (Lo-Ach) had lower levels of enjoyment and commitment. Conclusion - In general, these Masters athletes enjoyed their participation, they were committed, they had high perceptions of ability and belonging, and they were predominantly intrinsically motivated. The implications of these motivational profiles for Masters athletes are discussed from both theoretical and applied perspectives

NLRP3 inflammasome plays a key role in the regulation of intestinal homeostasis.

BACKGROUND:: Attenuated innate immune responses to the intestinal microbiota have been linked to the pathogenesis of Crohn's disease (CD). Recent genetic studies have revealed that hypofunctional mutations of NLRP3, a member of the NOD-like receptor (NLR) superfamily, are associated with an increased risk of developing CD. NLRP3 is a key component of the inflammasome, an intracellular danger sensor of the innate immune system. When activated, the inflammasome triggers caspase-1-dependent processing of inflammatory mediators, such as IL-1β and IL-18. METHODS:: In the current study we sought to assess the role of the NLRP3 inflammasome in the maintenance of intestinal homeostasis through its regulation of innate protective processes. To investigate this role, Nlrp3(-/-) and wildtype mice were assessed in the dextran sulfate sodium and 2,4,6-trinitrobenzenesulfonic acid models of experimental colitis. RESULTS:: Nlrp3(-/-) mice were found to be more susceptible to experimental colitis, an observation that was associated with reduced IL-1β, reduced antiinflammatory cytokine IL-10, and reduced protective growth factor TGF-β. Macrophages isolated from Nlrp3(-/-) mice failed to respond to bacterial muramyl dipeptide. Furthermore, Nlrp3-deficient neutrophils exhibited reduced chemotaxis and enhanced spontaneous apoptosis, but no change in oxidative burst. Lastly, Nlrp3(-/-) mice displayed altered colonic β-defensin expression, reduced colonic antimicrobial secretions, and a unique intestinal microbiota. CONCLUSIONS:: Our data confirm an essential role for the NLRP3 inflammasome in the regulation of intestinal homeostasis and provide biological insight into disease mechanisms associated with increased risk of CD in individuals with NLRP3 mutations. (Inflamm Bowel Dis 2010)

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis

Objective: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Methods: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets. Results: In the overall case–control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10−24; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76–2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21–3.20, p = 2.00 × 10−16). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32–3.52, p = 2.00 × 10−16) increased risk of CVT compared with individuals with blood group O. Interpretation: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777–788