Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

A Retrospective Analysis of the Haemodynamic and Metabolic Effects of Fluid Resuscitation in Vietnamese Adults with Severe Falciparum Malaria

BACKGROUND: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults. METHODS: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. RESULTS: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2) (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r(s) = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO(2)/FiO(2) ratio). There was no correlation between the oxygen delivery (DO(2)) and base deficit at the 63 time-points where they were assessed simultaneously (r(s) = -0.09, p = 0.46). CONCLUSIONS: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

. Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.Using a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.Theoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled

Managing sedentary behavior to reduce the risk of diabetes and cardiovascular disease

Modern human environments are vastly different from those of our forebears. Rapidly advancing technology in transportation, communications, workplaces, and home entertainment confer a wealth of benefits, but increasingly come with costs to human health. Sedentary behavior—too much sitting as distinct from too little physical activity—contributes adversely to cardiometabolic health outcomes and premature mortality. Findings from observational epidemiology have been synthesized in meta-analyses, and evidence is now shifting into the realm of experimental trials with the aim of identifying novel mechanisms and potential causal relationships. We discuss recent observational and experimental evidence that makes a compelling case for reducing and breaking up prolonged sitting time in both the primary prevention and disease management contexts. We also highlight future research needs, the opportunities for developing targeted interventions, and the potential of population-wide initiatives designed to address too much sitting as a health risk

Perspectives on a ‘Sit Less, Move More’ Intervention in Australian Emergency Call Centres

Background: Prolonged sitting is associated with increased risk of chronic diseases. Workplace programs that aim to reduce sitting time (sit less) and increase physical activity (move more) have targeted desk-based workers in corporate and university settings with promising results. However, little is known about 'move more, sit less' programs for workers in other types of jobs and industries, such as shift workers. This formative research examines the perceptions of a 'sit less, move more' program in an Australian Emergency Call Centre that operates 24 hours per day, 7 days per week.  Methods: Participants were employees (N = 39, 72% female, 50% aged 36-55 years) recruited from Emergency Services control centres located in New South Wales, Australia. The 'sit less, move more' intervention, consisting of emails, posters and timer lights, was co-designed with the management team and tailored to the control centre environment and work practices, which already included electronic height-adjustable sit-stand workstations for all call centre staff. Participants reported their perceptions and experiences of the intervention in a self-report online questionnaire, and directly to the research team during regular site visits. Questionnaire topics included barriers and facilitators to standing while working, mental wellbeing, effects on work performance, and workplace satisfaction. Field notes and open-ended response data were analysed in an iterative process during and after data collection to identify the main themes.  Results: Whilst participants already had sit-stand workstations, use of the desks in the standing position varied and sometimes were contrary to expectations (e.g, less tired standing than sitting; standing when experiencing high call stress). Participants emphasised the "challenging" and "unrelenting" nature of their work. They reported sleep issues ("always tired"), work stress ("non-stop demands"), and feeling mentally and physically drained due to shift work and length of shifts. Overall, participants liked the initiative but acknowledged that their predominantly sitting habits were entrenched and work demands took precedence.  Conclusions: This study demonstrates the low acceptability of a 'sit less, move more' program in shift workers in high stress environments like emergency call centres. Work demands take priority and other health concerns, like poor sleep and high stress, may be more salient than the need to sit less and move more during work shifts

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children.

BACKGROUND: Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. METHODS: We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. RESULTS: Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. CONCLUSIONS: Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period