The Impact of Sleep on Mental Toughness: Evidence From Observational and N-of-1 Manipulation Studies in Athletes

This is the author accepted manuscript. The final version is available from American Psychological Association via the DOI in this recordhe purpose of this study was to explore the direction and magnitude of the relationship between sleep and mental toughness and examine the effect of time in bed extension and restriction on mental toughness. Study 1 was an observational study examining the relationship between sleep quality and duration (hours) and mental toughness in 181 participants. Winsorized correlations revealed both longer sleep duration (ρω = .176 [.033, .316], p = .016) and higher quality (ρω = .412 [.270, .541], p ≤ .001) were associated with increased mental toughness. Follow-up regression analyses revealed sleep quality (b = 0.177, [0.117, 0,238], p ≤ .001), but not sleep duration (b = 0.450, [0.3254, 1.22], p = .256), predicted mental toughness score. In Study 2, we utilized a longitudinal N-of-1 influenced methodology with 6 participants to further examine whether manipulated time in bed (i.e., sleep duration) influenced mental toughness. Participants recorded sleep quality, duration, and mental toughness over 5 weekdays during 2 separate 2-week periods of baseline (normal sleeping pattern) followed by manipulated time in bed (counterbalanced 9 hr or 5 hr). Visual analyses (including determination of nonoverlapping data points between baseline and intervention weeks) revealed reduced time in bed negatively impacted the mental toughness of 4 of the participants. Social validation interviews were conducted to further explore participants' perceptions of the sleep manipulation. A cumulative effect of reduced sleep on mental toughness was noted by specific individuals. In addition, participants identified potential buoys of mental toughness in the absence of sleep

An exploratory case study of mental toughness variability and potential influencers over 30 Days

This is the final version. Available from the publisher via the DOI in this record.The purpose of this study was to explore whether mental toughness varies across a 30-day training block and whether such variability is associated with specific antecedents. This exploratory case study research investigated mental toughness variability using the Mental Toughness Index (MTI) with thirteen elite master runners across a series of self-selected training sessions, followed by interviews and follow-up questionnaires, to identify primary influencers of variability. There were significant differences in the MTI scores between baseline (before the training period), and the minimum and the maximum reported score over five self-selected training sessions (p's < 0.004). The proceeding follow-up interviews and questionnaires then provided insights into factors influencing this intra-individual variability. These higher-level themes included foundational wellbeing, specific preparation, and actions utilized in the moment. This study is the first to demonstrate within-person MTI variability across specific training sessions and provides initial insights for both athletes and practitioners into potential influencers of mental toughness

Room-Temperature One-Pot Synthesis of pH-Responsive Pyridine-Functionalized Carbon Surfaces

Carbon surfaces (glassy carbon, graphite, and boron-doped diamond) were functionalized with layers composed of linked pyridinium and pyridine moieties using simple electrochemical reduction of trifluoroacetylpyridinium. The pyridinium species was generated in situ in solution by the reaction of trifluoroacetic anhydride and pyridine precursors and underwent electrochemical reduction at −1.97 V vs Fc/Fc+, as determined by cyclic voltammetry. The pyridine/pyridinium films were electrodeposited at room temperature, on a timescale of minutes, and were characterized using X-ray photoelectron spectroscopy. The as-prepared films have a net positive charge in aqueous solution at pH 9 and below due to the pyridinium content, confirmed by the electrochemical response of differently charged redox molecules at the functionalized surfaces. The positive charge can be enhanced further through protonation of the neutral pyridine component by controlling the solution pH. Moreover, the nitrogen-acetyl bond can be cleaved through base treatment to purposefully increase the neutral pyridine proportion of the film. This results in a surface that can be “switched” from functionally near neutral to a positive charge by treatment in basic and acidic solutions, respectively, through manipulation of the protonation state of the pyridine. The functionalization process demonstrated here is readily achievable at a fast timescale at room temperature and hence can allow for rapid screening of surface properties. Such functionalized surfaces present a means to test in isolation the specific catalytic performance of pyridinic groups toward key processes such as oxygen and CO2 reduction

A 3000-mile tour of mental toughness: An autoethnographic exploration of mental toughness intra-individual variability in endurance sport

This is the author accepted manuscript. The final version is available from Routledge via the DOI in this recordMental toughness has garnered considerable attention over the past two decades because of the perception that this psychological construct influences an athlete’s ability to strive, thrive, and survive in sport. However, few researchers have explored the lived experiences of mental toughness within endurance sport. Analysis of lived experiences could help reveal how an athlete demonstrates (or does not demonstrate) mental toughness in real-world settings and provide insights for researchers, coaches and athletes in the future. The current autoethnographic approach offers an alternative perspective to supplement the existing mental toughness literature, and provides the most appropriate format to analyze the within-person mental toughness element at the core of this research study. The study recounts and analyses the personal experience of mental toughness across a trilogy of cycling, triathlon, and running endurance events by a single athlete over a 5-month period. The main findings focus on the variability of perceived mental toughness at different stages of competition and training and identify potential factors driving the notable fluctuation in levels of mental toughness. Factors identified as increasing this within-person mental toughness included anger, love, competition, encouragement and the recognition of a last chance to achieve meaningful goals. These findings are expected to support future research into within-person mental toughness and the practical application across a broader spectrum of settings

The impact of chromosomal translocation locus and fusion oncogene coding sequence in synovial sarcomagenesis.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotype-phenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology

Impact of lung function and baseline clinical characteristics on patient-reported outcome measures in systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: The SENSCIS® trial demonstrated a significant reduction of lung function decline in patients with systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD) treated with nintedanib, but no significant effect on health-related quality of life (HRQoL). To assess whether SSc/SSc-ILD severity and large changes in lung function correlate with HRQoL, a post-hoc analysis of SENSCIS®, aggregating treatment arms, was undertaken. METHODS: Patient-reported outcome (PRO) measures (St. George's Respiratory Questionnaire [SGRQ], Functional Assessment of Chronic Illness Therapy [FACIT]-Dyspnoea, and Health Assessment Questionnaire-Disability Index [HAQ-DI], incorporating the Scleroderma Health Assessment Questionnaire visual analogue scale [SHAQ VAS]) at baseline and week 52 were assessed for associations to SSc-ILD severity. RESULTS: At baseline and at week 52, forced vital capacity (FVC) 30% fibrosis on high-resolution computed tomography at baseline demonstrated worse PRO measure scores at week 52. After 1 year, patients with a major (>10%) improvement/worsening in FVC demonstrated corresponding improvement/worsening in SGRQ and other PRO measures, significant for the SGRQ symptom domain (p< 0.001). CONCLUSION: Severe SSc-ILD and major deteriorations in lung function have important impacts on HRQoL. Treatments that slow lung function decline and prevent severe SSc-ILD are important to preserve HRQoL. TRIAL REGISTRATION: clinicaltrials.gov, www.clinicaltrials.gov, NCT02597933

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

Distinct routes of lineage development reshape the human blood hierarchy across ontogeny.

In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.This work was supported by Postdoctoral Fellowship Awards from Canadian Institute of Health Research (CIHR) to FN and SZ. SZ is supported by (Aplastic Anemia). FN is a recipient of a scholar’s research award from the Ontario Institute of Cancer Research (OICR), through generous support from the Ontario Ministry of Research and Innovation. Research in EL laboratory is supported by a Wellcome Trust Sir Henry Dale Fellowship and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. Work in the Dick laboratory is supported by grants from the CIHR, Canadian Cancer Society, Terry Fox Foundation, Genome Canada through the Ontario Genomics Institute, OICR with funds from the province of Ontario, a Canada Research Chair and the Ontario Ministry of Health and Long Term Care (OMOHLTC).This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aab211

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

Genetic diversity and population structure of Ascochyta rabiei from the western Iranian Ilam and Kermanshah provinces using MAT and SSR markers

Knowledge of genetic diversity in A. rabiei provides different levels of information that are important in the management of crop germplasm resources. Gene flow on a regional level indicates a significant potential risk for the regional spread of novel alleles that might contribute to fungicide resistance or the breakdown of resistance genes. Simple sequence repeat (SSR) and mating type (MAT) markers were used to determine the genetic structure, and estimate genetic diversity and the prevalence of mating types in 103 Ascochyta rabiei isolates from seven counties in the Ilam and Kermanshah provinces of western Iran (Ilam, Aseman abad, Holaylan, Chardavol, Dareh shahr, Gilangharb, and Sarpul). A set of 3 microsatellite primer pairs revealed a total of 75 alleles; the number of alleles varied from 15 to 34 for each marker. A high level of genetic variability was observed among A. rabiei isolates in the region. Genetic diversity was high (He = 0.788) within populations with corresponding high average gene flow and low genetic distances between populations. The smallest genetic distance was observed between isolates from Ilam and Chardavol. Both mating types were present in all populations, with the majority of the isolates belonging to Mat1-1 (64%), but within populations the proportions of each mating type were not significantly different from 50%. Results from this study will be useful in breeding for Ascochyta blight-resistant cultivars and developing necessary control measures