The Molecular Evolution of Melanoma Distant Metastases.

The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH analysis revealed cancer cell fractions with monotonic copy number alterations, including PHIP gain and PTEN loss, in the metastatic cascade. By contrast, the cancer cell fraction with copy number alterations for BPTF and MITF was reduced in lymph node metastases but increased in distant metastases. Separately, the cancer cell fraction with NCOA3 copy number alteration was comparable between primary tumors and lymph node metastases yet increased in distant metastases. These results suggest enrichment of the phosphoinositide 3-kinase and MITF pathways in the transition through the metastatic cascade. By contrast, next-generation sequencing analysis did not identify a consistent pattern of changes in variant allele frequency while revealing several intriguing findings, including decreased variant allele frequency in distant metastases and distinct drivers in lymph node versus distant metastases. These results provide evidence that distant melanoma metastasis does not always emanate from lymph node metastasis. These results enhance our understanding of clonal patterns of melanoma metastasis, with possible implications for targeted therapy and metastasis competency.

Efficacy and Safety of Ponesimod Compared with Teriflunomide in Female Patients with Relapsing Multiple Sclerosis: Findings from the Pivotal OPTIMUM Study.

Background: Multiple sclerosis (MS) is threefold more prevalent in women than men. However, sex-specific efficacy analysis for MS disease-modifying therapies is not typically performed. Methods: Post hoc analyses of data from female patients enrolled in the phase 3, double-blind OPTIMUM study of relapsing MS were carried out. Eligible adults were randomized to ponesimod 20 mg or teriflunomide 14 mg once daily for up to 108 weeks. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included change in symptom domain of Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) at week 108, number of combined unique active lesions (CUALs) per year on magnetic resonance imaging, and time to 12- and 24-week confirmed disability accumulation (CDA). Results: A total of 735 female patients (581 of childbearing potential) were randomized to ponesimod (n = 363, 49.4%) or teriflunomide (n = 372, 50.6%). Relative risk reduction in the ARR for ponesimod versus teriflunomide was 33.1% (mean, 0.192 vs. 0.286, respectively; p < 0.002). Mean difference in FSIQ-RMS for ponesimod versus teriflunomide was -4.34 (0.12 vs. 4.46; p = 0.002); rate ratio in CUALs per year, 0.601 (1.45 vs. 2.41; p < 0.0001), and hazard ratio for time to 12- and 24-week CDA risk estimates, 0.83 (10.7% vs. 12.9%; p = 0.38) and 0.91 (8.8% vs. 9.7%; p = 0.69), respectively. Incidence of treatment-emergent adverse events was similar between treatment groups (89.0% and 90.1%). Conclusions: Analyses demonstrate the efficacy and safety of ponesimod, versus active comparator, for women with relapsing MS, supporting data-informed decision-making for women with MS. Clinical Trial Registration Number: NCT02425644.

Barriers to colonoscopy in UK colorectal cancer screening programmes: Qualitative interviews with ethnic minority groups.

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom. METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had not necessarily been invited for colonoscopy. All interviews were conducted in the participant's first language and were assessed using Framework-analysis, in line with a conceptual framework developed from previous interviews with healthcare professionals. RESULTS: Five thematic groups of barriers and facilitators were developed: 'Locus of control', 'Cultural attitudes and beliefs', 'Individual beliefs, knowledge and personal experiences with colonoscopy and cancer', 'Reliance on family and friends' and 'Health concerns'. Differences were observed, between ethnic groups, for: 'Locus of control', 'Cultural attitudes and beliefs' and 'Reliance on family and friends'. Black and South Asian participants frequently described the decision to attend colonoscopy as lying with 'God' (Muslims, specifically), 'the doctor', or 'family' (Locus of control). Black and South Asian participants also reported relying on friends and family for 'language, transport and emotional support' (Reliance on family and friends). Black-African participants, specifically, described cancer as 'socially taboo' (Cultural attitudes and beliefs). CONCLUSIONS: The results highlight several targets for culturally-tailored interventions to make colonoscopy more equitable.

Maternal health expert feedback on the attributes of a predictive analytics tool to improve pregnancy-related cardiovascular and mental health outcomes in the United States.

Identify pregnancy-related challenges and opportunities to improve maternal health care in the United States and understand the potential role of predictive analytics tool(s) in bridging the existing gaps, specifically, in CVD (cardiovascular disease) and depression. Experts in maternal health care, research, patient advocacy, CVD, psychiatry, and technology were interviewed during February and March of 2020. Additionally, published literature was reviewed to assess existing data, insights, and best practices that might help develop effective predictive analytics tool(s). The majority (78%) of the 18 experts interviewed were women. The feedback revealed several insights, including multiple barriers to diagnosis and treatment of pregnancy-related CVD and depression. In experts' collective opinion, predictive analytics could play an important role in maternal health care and in limiting pregnancy-related CVD and depression, but it must be grounded in quality data and integrate with existing health management systems. A holistic approach to maternal health that factors in racial-ethnic, regional, and socioeconomic disparities is needed that starts with preconception counseling and continues through 1 year postpartum. Predictive analytics tool(s) that are based on diverse and high-quality data could bridge some of the existing gaps in maternal health care and potentially help limit pregnancy-related CVD and depression.

Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials.

The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18-64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women-esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men-esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women-esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men-esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).

Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. adults.

BACKGROUND: The success of vaccination efforts to curb the COVID-19 pandemic will require broad public uptake of immunization and highlights the importance of understanding factors associated with willingness to receive a vaccine. METHODS: U.S. adults aged 65 and older enrolled in the HeartlineTM clinical study were invited to complete a COVID-19 vaccine assessment through the HeartlineTM mobile application between November 6-20, 2020. Factors associated with willingness to receive a COVID-19 vaccine were evaluated using an ordered logistic regression as well as a Random Forest classification algorithm. RESULTS: Among 9,106 study participants, 81.3% (n = 7402) responded and had available demographic data. The majority (91.3%) reported a willingness to be vaccinated. Factors most strongly associated with vaccine willingness were beliefs about the safety and efficacy of COVID-19 vaccines and vaccines in general. Women and Black or African American respondents reported lower willingness to vaccinate. Among those less willing to get vaccinated, 66.2% said that they would talk with their health provider before making a decision. During the study, positive results from the first COVID-19 vaccine outcome study were released; vaccine willingness increased after this report. CONCLUSIONS: Even among older adults at high-risk for COVID-19 complications who are participating in a longitudinal clinical study, 1 in 11 reported lack of willingness to receive COVID-19 vaccine in November 2020. Variability in vaccine willingness by gender, race, education, and income suggests the potential for uneven vaccine uptake. Education by health providers directed toward assuaging concerns about vaccine safety and efficacy can help improve vaccine acceptance among those less willing. TRIAL REGISTRATION: Clinicaltrials.gov NCT04276441.

The influence of bait on remote underwater video observations in shallow-water coastal environments associated with the North-Eastern Atlantic.

The use of baited remote underwater video (BRUV) for examining and monitoring marine biodiversity in temperate marine environments is rapidly growing, however many aspects of their effectiveness relies on assumptions based on studies from the Southern Hemisphere. The addition of bait to underwater camera systems acts as a stimulus for attracting individuals towards the camera field of view, however knowledge of the effectiveness of different bait types in northern temperate climbs is limited, particularly in dynamic coastal environments. Studies in the Southern Hemisphere indicate that oily baits are most effective whilst bait volume and weight do not impact BRUV effectiveness to any great degree. The present study assesses the influence of four bait types (mackerel, squid, crab and no bait (control)) on the relative abundance, taxonomic diversity and faunal assemblage composition at two independent locations within the North-Eastern Atlantic region; Swansea Bay, UK and Ria Formosa Lagoon, Portugal. Two different bait quantities (50 g and 350 g) were further trialled in Swansea Bay. Overall, patterns showed that baited deployments recorded statistically higher values of relative abundance and taxonomic diversity when compared to un-baited deployments in Swansea Bay but not in Ria Formosa Lagoon. No statistical evidence singled out one bait type as best performing for attracting higher abundances and taxonomic diversity in both locations. Faunal assemblage composition was however found to differ with bait type in Swansea Bay, with mackerel and squid attracting higher abundances of scavenging species compared to the crab and control treatments. With the exception of squid, bait quantity had minimal influence on bait attractiveness. It is recommended for consistency that a minimum of 50 g of cheap, oily fish such as mackerel is used as bait for BRUV deployments in shallow dynamic coastal environments in the North-Eastern Atlantic Region.

Airway narrowing and response to simulated deep inspiration in bronchial segments from subjects with fixed airflow obstruction.

The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed (n = 12) or "fixed" obstructed (n = 6) on the basis of preoperative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P), was also measured preoperatively. M/P was reduced in the obstructed group (P = 0.02). Postoperatively, bronchial segments were obtained from resected tissue, and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine (P = 0.01) and the volume fraction of ECM within the ASM layer (P = 0.02) were increased in the obstructed group, without a change in ASM thickness. Whereas bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P (bronchodilation/less bronchoconstriction) in vivo (P = 0.03). The volume fraction of ECM was inversely related to forced expiratory volume in 1 s FEV1 %predicted (P = 0.04) and M/P (P = 0.01). Results show that in subjects with fixed airflow obstruction the mechanical behavior of the airway wall is altered and there is a contemporaneous shift in the structural composition of the ASM layer.NEW & NOTEWORTHY Cartilaginous airways from subjects with fixed airflow obstruction have an increase in the volume fraction of extracellular matrix within the airway smooth muscle layer. These airways are also intrinsically more reactive to a contractile stimulus, which is expected to contribute to airway hyperresponsiveness in this population, often attributed to geometric mechanisms. In view of these results, we speculate on how changes in extracellular matrix may impact airway mechanics.

The importance of history, language, change and challenge: What Vygotsky can teach sports coaches

AIMS: In recent years, recognition of the pedagogical nature of coaching has gained increasing traction. However, within this line of inquiry, only limited attention has been given to the work of Lev Vygotsky. The aim of this article is to construct a more comprehensive case about how Vygotsky's principal ideas can aid our understanding of both the act and process of sports coaching. METHODS: The method involves constructing a case from Vygotsky's original work, and how it has been interpreted by others, related to the applicability of using some of his concepts to further our understanding of sports coaching practice. The case presented represents an interpretive and considered approach to the question and task at hand. DISCUSSION: The discussion is centred on the utility of Vygotsky's theorising to sports coaching practice. In particular his advocacy of (1) the cultural-historical perspective; (2) the claim of language as the greatest mediator in learning; (3) how perezhivane contributes to such knowledge generation; (4) the zone of proximal development and the role of the 'more capable other' within it; and (5) the dialectical approach, focussing on the dynamic relationship between everyday and scientific concepts, are given primacy. CONCLUSION: Finally, a reflective conclusion summarises the main points made and suggests possible future courses of action.(AU)

Airway remodelling in COPD: It's not asthma!

COPD is defined as airflow limitation that is not reversed by treatment. In asthma, airflow limitation is not only reversible, but also inducible. This is called 'airway hyperresponsiveness' (AHR) and is associated with thickening of the airway wall, predominantly the layer of airway smooth muscle, due to more cells, bigger cells and more extracellular matrix (ECM) in proportion to the increase in smooth muscle. AHR is also observed in COPD if the changes in airflow are expressed as a percent of the baseline lung function. However, the absolute change in baseline lung function that can be induced in COPD is actually less than that seen in normal subjects, suggesting that the airways in COPD are resistant not only to opening, but also to closing. This observation agrees with physiological measures showing increased airway wall stiffness in COPD. Like asthma, airway wall thickness is increased in COPD, including the layer of smooth muscle. Unlike asthma, however, fixed airflow obstruction appears to be characterized by a disproportionate increase in the ECM within the smooth muscle layer. In this review, we summarize the studies of airway matrix deposition in COPD and put forward the proposal that the airway remodelling in COPD is different from that in asthma and call for a systematic analysis of airway matrix deposition in COPD.

The effect of asthma on the perimeter of the airway basement membrane.

When comparing the pathology of airways in individuals with and without asthma, the perimeter of the basement membrane (Pbm) is used as a marker of airway size, as it is independent of airway smooth muscle shortening or airway collapse. The extent to which the Pbm is itself altered in asthma has not been quantified. The aim of this study was to compare the Pbm from the same anatomical sites in postmortem lungs from subjects with (n = 55) and without (n = 30) asthma (nonfatal or fatal). Large and small airways were systematically sampled at equidistant "levels" from the apical segment of the left upper lobes and anterior and basal segments of the left lower lobes of lungs fixed in inflation. The length of the Pbm was estimated from cross sections of airway at each relative level. Linear mixed models were used to investigate the relationships between Pbm and sex, age, height, smoking status, airway level, and asthma group. The final model showed significant interactions between Pbm and airway level in small (<3 mm) airways, in subjects having asthma (P < 0.0001), and by sex (P < 0.0001). No significant interactions for Pbm between asthma groups were observed for larger airways (equivalent to a diameter of ∼3 mm and greater) or smoking status. Asthma is not associated with remodeling of the Pbm in large airways. In medium and small airways, the decrease in Pbm in asthma (≤20%) would not account for the published differences in wall area or area of smooth muscle observed in cases of severe asthma.

Distribution of airway smooth muscle remodelling in asthma: relation to airway inflammation.

BACKGROUND AND OBJECTIVE: Pathological phenotypes of asthma have been based predominantly on inflammation, rather than airway wall remodelling. Differences in the distribution of airway smooth muscle (ASM) remodelling between large and small airways may affect clinical outcomes in asthma. The aim of this study was to examine the distribution of ASM remodelling and its relation to airway inflammation. METHODS: Post-mortem cases of asthma (n = 68) were categorized by the distribution of increased thickness of the ASM layer (relative to nonasthmatic controls, n = 37), into 'large only' (LO, n = 15), 'small only' (SO, n = 4) 'large/small' (LS, n = 24) or no increase (NI, n = 25). Subject characteristics, ASM and airway wall dimensions and inflammatory cell numbers were compared between groups. RESULTS: Apart from reduced clinical severity of asthma in NI cases (P = 0.002), subject characteristics did not distinguish asthma groups. Compared with control subjects, ASM cell number, reticular basement membrane thickness, airway wall thickness, percent muscle shortening and eosinophil number were increased (P < 0.05) in both large and small airways in LS cases and only the large airways in LO cases. Increased numbers of neutrophils were observed only in the small airways of LO cases. CONCLUSIONS: Distinct distributions of ASM remodelling are seen in asthma. Pathology limited to the small airways was uncommon. Increased thickness of the ASM layer was associated with airway remodelling and eosinophilia, but not neutrophilia. These data support the presence of distinct pathological phenotypes based on the site of increased ASM.

Estimating airway smooth muscle cell volume and number in airway sections. Sources of variability.

Hypertrophy and hyperplasia of airway smooth muscle (ASM) cells are features of asthma that can be assessed in airway transverse sections using stereologically derived parameters. However, little is known about the variability of these parameters within and between airways. The aim of the present study was to assess sources of variation in the measurement of the area of the ASM layer (AASM), and the volume fraction of ASM cells (VVASM) and numerical density of ASM cells within that layer. AASM increased by up to 12% in 4-µm sections, and 28% in 30-µm sections, compared with 0.5-µm sections. AASM was greater (P < 0.05) in large than in small airways, and varied by up to 28% along segments of large airways. Numerical density of ASM cell estimates around the airway circumference varied by less than 10% if 40 random high-power fields were sampled. VVASM was most accurately estimated on 0.5-µm, rather than 4- or 30-µm sections, and was less (P < 0.05) in large than in small airways. The coefficients of variation for VVASM were less than 10% along airway segments. We found that variation of parameters used to estimate ASM cell number or size could be minimized with adequate sampling frequency around or along airway segments. Section thickness was positively related to the measured area of ASM on transverse airway sections. Thin (0.5-µm) sections should be used to estimate tissue volume fractions, which vary little within and between airways of similar size. Airway size contributes most to the variation in estimating parameters of the ASM layer.

Do coaches orchestrate? The working practices of elite Portuguese coaches.

PURPOSE: Although the concept of orchestration has resonated well with coaches and students of coaching, it remains quite an immature theorization lacking empirical evidence. Consequently, the purpose of this study was to explore the practice of expert Portuguese coaches from the perspective of orchestration. The specific objectives related to examining if and how coaches manipulate contexts and relationships toward desired ends, if and how they steer and/or stage-manage events, and precisely what informs their actions. METHODS: Data were gathered through a series of semi-structured interviews with 5 top-level Portuguese coaches from a variety of sports. The coaches were selected through purposive sampling. The interviews were taped and transcribed verbatim so that an accurate record of the data gathered was obtained. The data were subject to both inductive and deductive examination through a process of thematic analysis. RESULTS: The categorical themes resulting from the process of data analysis included (a) the need amongst the coaches "for stakeholder buy-in," (b) "generating an illusion of empowerment" among both staff and athletes to ensure compliance, (c) "scaffolding the context to create a controlled instability" and (d) "detailed noticing to inform action." CONCLUSION: The coaches featured in this study were found to carefully and strategically consider their actions and behaviors; particularly concerning the generation of others' compliance and respect. Consequently, in giving further credence to the notions of power, social obligation, and the flexible scaffolding of learning, the findings support the notion that the concept of orchestration deserves further exploration and development in order to better understand the coach's role.

Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma.

The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma (n = 5) or had no history of asthma (n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM (P = 0.014), greater maximal airway narrowing under static conditions (P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer (r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group (P = 0.0001) and the group with a history of asthma (P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing (P = 0.02; r = -0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.

Airway smooth muscle hypertrophy and hyperplasia in asthma.

RATIONALE: Increased thickness of the airway smooth muscle (ASM) layer in asthma may result from hyperplasia or hypertrophy of muscle cells or increased extracellular matrix (ECM). OBJECTIVES: To relate ASM hypertrophy, ASM hyperplasia, and deposition of ECM to the severity and duration of asthma. METHODS: Airways from control subjects (n = 51) and from cases of nonfatal (n = 49) and fatal (n = 55) asthma were examined postmortem. Mean ASM cell volume (V(C)), the number of ASM cells per length of airway (N(L)), and the volume fraction of extracellular matrix (f(ECM)) within the ASM layer were estimated. Comparisons between subject groups were made on the basis of general linear regression models. MEASUREMENTS AND MAIN RESULTS: Mean V(C) was increased in the large airways of cases of nonfatal asthma (P = 0.015) and fatal asthma (P < 0.001) compared with control subjects. N(L) was similar in nonfatal cases and control subjects but increased in large (P < 0.001), medium (P < 0.001), and small (P = 0.034) airways of cases of fatal asthma compared with control subjects and with nonfatal cases (large and medium airways, P ≤ 0.003). The f(ECM) was similar in cases of asthma and control subjects. Duration of asthma was associated with a small increase in N(L). CONCLUSIONS: Hypertrophy of ASM cells occurs in the large airways in both nonfatal and fatal cases of asthma, but hyperplasia of ASM cells is present in the large and small airways in fatal asthma cases only. Both are associated with an absolute increase in ECM. Duration of asthma has little or no effect on ASM hypertrophy or hyperplasia or f(ECM).

Responsiveness of the human airway in vitro during deep inspiration and tidal oscillation.

In healthy individuals, deep inspiration produces bronchodilation and reduced airway responsiveness, which may be a response of the airway wall to mechanical stretch. The aim of this study was to examine the in vitro response of isolated human airways to the dynamic mechanical stretch associated with normal breathing. Human bronchial segments (n = 6) were acquired from patients without airflow obstruction undergoing lung resection for pulmonary neoplasms. The side branches were ligated and the airways were mounted in an organ bath chamber. Airway narrowing to cumulative concentrations of acetylcholine (3 × 10(-6) M to 3 × 10(-3) M) was measured under static conditions and in the presence of "tidal" oscillations with intermittent "deep inspiration." Respiratory maneuvers were simulated by varying transmural pressure using a motor-controlled syringe pump (tidal 5 to 10 cmH(2)O at 0.25 Hz, deep inspiration 5 to 30 cmH(2)O). Airway narrowing was determined from decreases in lumen volume. Tidal oscillation had no effect on airway responses to acetylcholine which was similar to those under static conditions. Deep inspiration in tidally oscillating, acetylcholine-contracted airways produced potent, transient (<1 min) bronchodilation, ranging from full reversal in airway narrowing at low acetylcholine concentrations to ∼50% reversal at the highest concentration. This resulted in a temporary reduction in maximal airway response (P < 0.001), without a change in sensitivity to acetylcholine. Our findings are that the mechanical stretch of human airways produced by physiological transmural pressures generated during deep inspiration produces bronchodilation and a transient reduction in airway responsiveness, which can explain the beneficial effects of deep inspiration in bronchial provocation testing in vivo.

An in-depth assessment of expert sprint coaches' technical knowledge.

Among the myriad issues addressed by current research are the sources of knowledge of coaches in terms of their implicit and/or explicit natures. What appears to remain unaddressed, however, is the arguably prior step of coaches' content knowledge; that is, what coaches know as opposed to how they know it. The aim of this study was to partially address this shortcoming by identifying the characteristics that expert coaches associate with good sprint running technique, in addition to where such knowledge was gleaned. Seven expert male sprint coaches participated in the study, with data being gathered through in-depth, semi-structured interviews. The data were inductively analysed using the ATLAS.ti 5.2 qualitative software. Four principal constructs emerged from the interview data. These included "posture", "hip position", "ground contact, and "arm action', with tacit, experiential sources, generated predominantly from conversations with respected peers, forming the basis of such knowledge. The findings are located within existing sprinting literature, before we summarize the main points made.