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Seventy six senior academics from 11 countries invite The BMJ ’s editors to reconsider their policy of rejecting qualitative research on the grounds of low priority. They challenge the journal to develop a proactive, scholarly, and pluralist approach to research that aligns with its stated mission

We made sex-based comparisons of rates of myofibrillar protein synthesis (MPS) and anabolic signaling after a single bout of high-intensity resistance exercise. Eight men (20 ± 10 yr, BMI = 24.3 ± 2.4) and eight women (22 ± 1.8 yr, BMI = 23.0 ± 1.9) underwent primed constant infusions of l-[ ring-13C6]phenylalanine on consecutive days with serial muscle biopsies. Biopsies were taken from the vastus lateralis at rest and 1, 3, 5, 24, 26, and 28 h after exercise. Twenty-five grams of whey protein was ingested immediately and 26 h after exercise. We also measured exercise-induced serum testosterone because it is purported to contribute to increases in myofibrillar protein synthesis (MPS) postexercise and its absence has been hypothesized to attenuate adaptative responses to resistance exercise in women. The exercise-induced area under the testosterone curve was 45-fold greater in men than women in the early (1 h) recovery period following exercise ( P < 0.001). MPS was elevated similarly in men and women (2.3- and 2.7-fold, respectively) 1–5 h postexercise and after protein ingestion following 24 h recovery. Phosphorylation of mTORSer2448 was elevated to a greater extent in men than women acutely after exercise ( P = 0.003), whereas increased phosphorylation of p70S6K1Thr389 was not different between sexes. Androgen receptor content was greater in men (main effect for sex, P = 0.049). Atrogin-1 mRNA abundance was decreased after 5 h recovery in both men and women ( P < 0.001), and MuRF-1 expression was elevated in men after protein ingestion following 24 h recovery ( P = 0.003). These results demonstrate minor sex-based differences in signaling responses and no difference in the MPS response to resistance exercise in the fed state. Interestingly, our data demonstrate that exercise-induced increases in MPS are dissociated from postexercise testosteronemia and that stimulation of MPS occurs effectively with low systemic testosterone concentrations in women.

Patients often start treatment to reduce fracture risk because of a bone mineral density T-score consistent with osteoporosis (≤ −2.5). Others with a T-score above −2.5 may be treated when there is a history of fragility fracture or when a fracture risk algorithm categorizes them as having a high risk for fracture. It is common to initiate therapy with a generic oral bisphosphonate, unless contraindicated, and continue therapy if the patient is responding as assessed by stability or an increase in bone mineral density. However, some patients may respond well to an oral bisphosphonate, yet remain with an unacceptably high risk for fracture. Recognition of this occurrence has led to the development of an alternative strategy: treat-to-target. This involves identifying a biological marker (treatment target) that represents an acceptable fracture risk and then initiating treatment with an agent likely to reach this target. If the patient is on a path to reaching the target with initial therapy, treatment is continued. If it appears the target will not be reached with initial therapy, treatment is changed to an agent more likely to achieve the goal.

Continuing professional development (CPD) is important to ensure teachers continuously maintain and update the best practice knowledge and skills needed for the profession. Limited research into CPD in physical education (PE-CPD) suggests that current provisions are largely ineffective, particularly regarding access, and the specific teaching of motor skills (e.g. throw, catch, run). Improved PE-CPD is clearly needed, and online programmes may provide a promising avenue for more accessible and effective delivery. Digital models of PE-CPD are in the early stages of use, and as yet we know very little about PE teachers’ experiences of online CPD. Thus, the present study aimed to (i) explore elementary school PE teachers’ perceptions of online PE-CPD; and (ii) provide recommendations on the development and provision of future online PE-CPD, with a particular focus on motor skill instruction and assessment. Twenty-two PE teachers participated in focus group discussions, which were analysed in NVivo 11 using an inductive thematic approach. Three major themes and several subthemes were developed from the data. First, there was significant teacher motivation and perceived need for online PE-CPD, mainly in relation to accessibility. Second, and despite this perceived need, teachers reported considerable caution around its use, especially regarding a perceived lack of a ‘community of practice’. Third, teachers provided multiple suggestions for future online PE-CPD design and delivery, including that it: (i) be evidence-based; (ii) provide pedagogical content knowledge and not just content knowledge; (iii) be informed by teachers and translatable to practice; (iv) facilitate communities of practice; (v) be interactive; (vi) be simple to navigate; and (vii) be highly visual. It is clear from teacher feedback that while online PE-CPD provides new opportunities, there are still significant limitations. This research provides novel insights and valuable recommendations that could optimise the success of future online PE-CPD offerings.

Background: There are two approaches to the differential examination of school motivation. The first is to examine motivation towards specific school subjects (between school subject differentiation). The second is to examine school motivation as a multidimensional concept that varies in terms of not only intensity but also quality (within school subject differentiation). These two differential approaches have led to important discoveries and provided a better understanding of student motivational dynamics. However, little research has combined these two approaches. Aims: This study examines young elementary students' motivations across school subjects (writing, reading, and maths) from the stance of self-determination theory. First, we tested whether children self-report different levels of intrinsic, identified, and controlled motivation towards specific school subjects. Second, we verified whether children self-report differentiated types of motivation across school subjects. Sample: Participants were 425 French-Canadian children (225 girls, 200 boys) from three elementary schools. Children were in Grades 1 (N=121), 2 (N=126), and 3 (N=178). Results: Results show that, for a given school subject, young elementary students self-report different levels of intrinsic, identified, and controlled motivation. Results also indicate that children self-report different levels of motivation types across school subjects. Our findings also show that most differentiation effects increase across grades. Some gender effects were also observed. Conclusion: These results highlight the importance of distinguishing among types of school motivation towards specific school subjects in the early elementary years.

Key points Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

Introduction: Self-management interventions in patients with chronic conditions have received increasing attention over the past few years, yet the meta-analyses encountered considerable heterogeneity in results. This suggests that the effectiveness of self-management interventions must be assessed in the context of which components are responsible for eliciting the effect and in which subgroups of patients the intervention works best. The aim of the present study is to identify condition-transcending determinants of success of self-management interventions in two parallel individual patient data meta-analyses of self-management trials in patients with congestive heart failure (CHF) and in patients with chronic obstructive pulmonary disease (COPD). Methods and analysis: Investigators of 53 randomised trials (32 in CHF and 21 in COPD) will be requested to share their de-identified individual patient data. Data will be analysed using random effects models, taking clustering within studies into account. Effect modification by age, sex, disease severity, symptom status, comorbid conditions and level of education will be assessed. Sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination: The de-identified individual patient data are used only for the purpose for which they were originally collected and for which ethical approval has been obtained by the original investigators. Knowledge on the effective ingredients of self-management programmes and identification of subgroups of patients in which those interventions are most effective will guide the development of evidence-based personalised self-management interventions for patients with CHF and COPD as well as with other chronic diseases. Trial registration number: PROSPERO: CRD42013004698.

Background: The impact of childhood epilepsy can only be appreciated by understanding that epilepsy comprises a set of complex neurobehavioral conditions with significant social consequences, and not simply disorders of recurrent seizures. Our objective is to describe the hypotheses and methodology behind a large prospective longitudinal study that is based on a conceptual framework for understanding health outcomes. The study will quantify the specific influences—direct, mediating or moderating—that various epilepsy, comorbid, child, and family variables exert on health over the early life course. Methods: The target population is 8- to 14-year-old children with epilepsy and their caregivers from across Canada. Children, caregivers, and health professionals are completing 17 measures at five visits over a 28-month period. We have selected measures based on content, the source of the items, psychometric properties, and provisions for child self-report. Our cross-sectional and longitudinal design includes a relational model for structural equation modeling of specific biomedical and psychosocial variables with hierarchical direction of influence. To measure change over time, we will use hierarchical linear modeling. Significance: This article reports the framework for interpreting future data. We believe that it will help researchers consider their methodology and encourage them to plan and execute longitudinal studies. Furthermore, the article will help clinical readers identify what to look for when evaluating outcomes research. It is our belief that the next generation of research to understand life-course effect in the lives of children and youth with chronic conditions and their families must occur over real time.

The capacity to focus one's attention for an extended period of time can be increased through training in contemplative practices. However, the cognitive processes engaged during meditation that support trait changes in cognition are not well characterized. We conducted a longitudinal wait-list controlled study of intensive meditation training. Retreat participants practiced focused attention (FA) meditation techniques for three months during an initial retreat. Wait-list participants later undertook formally identical training during a second retreat. Dense-array scalp-recorded electroencephalogram (EEG) data were collected during 6 min of mindfulness of breathing meditation at three assessment points during each retreat. Second-order blind source separation, along with a novel semi-automatic artifact removal tool (SMART), was used for data preprocessing. We observed replicable reductions in meditative state-related beta-band power bilaterally over anteriocentral and posterior scalp regions. In addition, individual alpha frequency (IAF) decreased across both retreats and in direct relation to the amount of meditative practice. These findings provide evidence for replicable longitudinal changes in brain oscillatory activity during meditation and increase our understanding of the cortical processes engaged during meditation that may support long-term improvements in cognition.

Objective Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects. Methods Glucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK β1β2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation. Results There was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle 2-deoxyglucose uptake, Akt phosphorylation and glucose transporter 4 (GLUT4) content independently of alterations in body mass. In WT, but not AMPK-MKO mice, R419 improved treadmill running capacity. Treatment with R419 increased muscle electron transport chain content and activity in WT mice; effects which were blunted in AMPK-MKO mice. Conclusions Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity. Highlights • The beneficial effects of a novel complex I inhibitor, R419, were examined in skeletal muscle AMPK deficient obese mice. • R419 improves skeletal muscle insulin sensitivity in obese mice. • R419 improves exercise capacity in obese mice via an AMPK dependent pathway. • These findings suggest that R419 may have therapeutic importance in improving exercise capacity and skeletal muscle insulin sensitivity.