The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Focus on the management of thunderclap headache: from nosography to treatment

Thunderclap headache (TCH) is an excruciating headache characterized by a very sudden onset. Recognition and accurate diagnosis of TCH are important in order to rule out the various, serious underlying brain disorders that, in a high percentage of cases, are the real cause of the headache. Primary TCH, which may recur intermittently and generally has a spontaneous, benign evolution, can thus be diagnosed only when all other potential underlying causes have been excluded through accurate diagnostic work up. In this review, we focus on the management of TCH, paying particular attention to the diagnostic work up and treatment of the condition

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

BACKGROUND Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer. We assessed the effect of this combination in men starting long-term androgen-deprivation therapy (ADT), using a multigroup, multistage trial design. METHODS We randomly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate (1000 mg daily) and prednisolone (5 mg daily) (combination therapy). Local radiotherapy was mandated for patients with node-negative, nonmetastatic disease and encouraged for those with positive nodes. For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease, treatment continued until radiologic, clinical, or prostate-specific antigen (PSA) progression; otherwise, treatment was to continue for 2 years or until any type of progression, whichever came first. The primary outcome measure was overall survival. The intermediate primary outcome was failure-free survival (treatment failure was defined as radiologic, clinical, or PSA progression or death from prostate cancer). RESULTS A total of 1917 patients underwent randomization from November 2011 through January 2014. The median age was 67 years, and the median PSA level was 53 ng per milliliter. A total of 52% of the patients had metastatic disease, 20% had node-positive or node-indeterminate nonmetastatic disease, and 28% had node-negative, nonmetastatic disease; 95% had newly diagnosed disease. The median follow-up was 40 months. There were 184 deaths in the combination group as compared with 262 in the ADT-alone group (hazard ratio, 0.63; 95% confidence interval [CI], 0.52 to 0.76; P<0.001); the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease. There were 248 treatment-failure events in the combination group as compared with 535 in the ADT-alone group (hazard ratio, 0.29; 95% CI, 0.25 to 0.34; P<0.001); the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease. Grade 3 to 5 adverse events occurred in 47% of the patients in the combination group (with nine grade 5 events) and in 33% of the patients in the ADT-alone group (with three grade 5 events). CONCLUSIONS Among men with locally advanced or metastatic prostate cancer, ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than ADT alone. (Funded by Cancer Research U.K. and others; STAMPEDE ClinicalTrials.gov number, NCT00268476, and Current Controlled Trials number, ISRCTN78818544.

The effects of repeated-sprint training on field-based fitness measures: a meta-analysis of controlled and non-controlled trials

Background: Repeated-sprint training appears to be an efficient and practical means for the simultaneous development of different components of fitness relevant to team sports. Objective: Our objective was to systematically review the literature and meta-analyse the effect of repeated-sprint training on a selection of field-based measures of athletic performance, i.e. counter-movement jump, 10 m sprint, 20 m sprint, 30 m sprint, repeated-sprint ability and high-intensity intermittent running performance. Data Sources: The SPORTDiscus, PubMed, MEDLINE and Web of Science databases were searched for original research articles. Search terms included 'repeated-sprint training', 'sprint training', 'aerobic endurance', 'repeated-sprint ability', 'counter-movement jump' and 'sprint performance'. Study Selection: Inclusion criteria included intervention consisting of a series of ≤10 s sprints with ≤60 s recovery; trained participants; intervention duration of 2–12 weeks; field-based fitness measures; running- or cycling-based intervention; published up to, and including, February 2014. Data Extraction: Our final dataset included six trials for counter-movement jump (two controlled trials), eight trials for 10 m sprint, four trials for 20 m sprint (three controlled trials), two trials for 30 m sprint, eight trials for repeated-sprint ability and three trials for high-intensity intermittent running performance. Analyses were conducted using comprehensive meta-analysis software. Uncertainty in the meta-analysed effect of repeated-sprint training was expressed as 95 % confidence limits (CL), along with the probability that the true value of the effect was trivial, beneficial or harmful. Magnitude-based inferences were based on standardised thresholds for small, moderate and large changes of 0.2, 0.6 and 1.2 standard deviations, respectively. Results: Repeated-sprint training had a likely small beneficial effect in non-controlled counter-movement jump trials (effect size 0.33; 95 % CL ±0.30), with a possibly moderate beneficial effect in controlled trials (0.63; 95 % CL ±0.44). There was a very likely small beneficial effect on 10 m sprint time in non-controlled trials (−0.42; 95 % CL ±0.24), with a possibly moderate beneficial effect on 20 m sprint time in non-controlled (−0.49; 95 % CL ±0.46) and controlled (−0.65; 95 % CL ±0.61) trials. Repeated-sprint training had a possibly large beneficial effect on 30 m sprint performance in non-controlled trials (−1.01; 95 % CL ±0.93), with possibly moderate beneficial effects on repeated-sprint ability (−0.62; 95 % CL ±0.25) and high-intensity intermittent running performance (−0.61; 95 % CL ±0.54). Conclusions: Repeated-sprint training can induce small to large improvements in power, speed, repeated-sprint ability and endurance, and may have relevance for training in team sports