Outcomes for Children Receiving Noninvasive Ventilation as the First-Line Mode of Mechanical Ventilation at Intensive Care Admission: A Propensity Score-Matched Cohort Study.

OBJECTIVES: To compare outcomes of children receiving noninvasive ventilation with those receiving invasive ventilation as first-line mode of mechanical ventilation following unplanned intensive care admission. DESIGN: Propensity score-matched cohort study analyzing data prospectively collected by the Pediatric Intensive Care Audit Network over 8 years (2007-2014). SETTING: Thirty-one PICUs in the United Kingdom and Ireland; twenty-one of whom submitted Pediatric Critical Care Minimum Dataset data for the entire study period. PATIENTS: Children consecutively admitted to study PICUs. Planned admissions following surgery, unplanned admissions from other hospitals, those on chronic ventilation, and those who did not receive mechanical ventilation on the day of PICU admission were excluded. INTERVENTIONS: Use of noninvasive ventilation, rather than invasive ventilation, as the first-line mode of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: PICU mortality, length of ventilation, length of PICU stay, and ventilator-free days at day 28. During the study period, there were 151,128 PICU admissions. A total of 15,144 admissions (10%) were eligible for analysis once predefined exclusion criteria were applied: 4,804 (31.7%) received "noninvasive ventilation first," whereas 10,221 (67.5%) received "invasive ventilation first"; 119 (0.8%) admissions could not be classified. Admitting PICU site explained 6.5% of the variation in first-line mechanical ventilation group (95% CI, 2.0-19.0%). In propensity score-matched analyses, receiving noninvasive ventilation first was associated with a significant reduction in mortality by 3.1% (95% CI, 1.7-4.6%), length of ventilation by 1.6 days (95% CI, 1.0-2.3), and length of PICU stay by 2.1 days (95% CI, 1.3-3.0), as well as an increase in ventilator-free days at day 28 by 3.7 days (95% CI, 3.1-4.3). CONCLUSIONS: Use of noninvasive ventilation as first-line mode of mechanical ventilation in critically ill children admitted to PICU in an unplanned fashion may be associated with significant clinical benefits. Further high-quality evidence regarding optimal patient selection and timing of initiation of noninvasive ventilation could lead to less variability in clinical care between institutions and improved patient outcomes

Multi-stakeholder perspectives of factors that influence contact centre call agent’s workplace physical activity and sedentary behaviour

Contact centre call agents are highly sedentary at work, which can negatively affect cardio-metabolic health. This qualitative cross-sectional study explored factors influencing call agents’ workplace physical activity (PA) and sedentary behaviour (SB), and perspectives on strategies to help agents move more and sit less at work. Semi-structured interviews and focus groups with call agents (n = 20), team leaders (n = 11) and senior staff (n = 12) across four contact centres were guided by the socio-ecological model and analysed thematically. Agents offered insights into the impact of high occupational sitting and low PA on their physical and mental health, and factors influencing their motivation to move more and sit less at work. Team leaders, although pivotal in influencing behaviours, identified their own workload, and agents’ requirement to meet targets, as factors influencing their ability to promote agents to move more and sit less at work. Further, senior team leaders offered a broad organisational perspective on influential factors, including business needs and the importance of return on investment from PA and SB interventions. Unique factors, including continuous monitoring of productivity metrics and personal time, a physical connection to their workstation, and low autonomy over their working practices, seemed to limit call agents’ opportunity to move more and sit less at work. Proposed strategies included acknowledgement of PA and SB within policy and job roles, height-adjustable workstations, education and training sessions and greater interpersonal support. Additionally, measuring the impact of interventions was perceived to be key for developing a business case and enhancing organisational buy-in. Multi-level interventions embedded into current working practices appear important for the multiple stakeholders, while addressing concerns regarding productivity

Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

Weighted-norm preconditioners for a multilayer tide model

We derive a linearized rotating shallow water system modeling tides, which can be discretized by mixed finite elements. Unlike previous models, this model allows for multiple layers stratified by density. Like the single-layer case [R. C. Kirby and T. Kernell, Comput. Math. Appl., 82 (2021), pp. 212–227], a weighted-norm preconditioner gives a (nearly) parameter-robust method for solving the resulting linear system at each time step, but the all-to-all coupling between the layers in the model poses a significant challenge to efficiency. Neglecting the inter-layer coupling gives a preconditioner that degrades rapidly as the number of layers increases. By a careful analysis of the matrix that couples the layers, we derive a robust method that requires solving a reformulated system that only involves coupling between adjacent layers. Numerical results obtained using Firedrake [F. Rathgeber et al., ACM Trans. Math. Software, 43 (2016), 24] confirm the theory

The lung inflammation and skeletal muscle wasting induced by subchronic cigarette smoke exposure are not altered by a high-fat diet in mice

Obesity and cigarette smoking independently constitute major preventable causes of morbidity and mortality and obesity is known to worsen lung inflammation in asthma. Paradoxically, higher body mass index (BMI) is associated with reduced mortality in smoking induced COPD whereas low BMI increases mortality risk. To date, no study has investigated the effect of a dietary-induced obesity and cigarette smoke exposure on the lung inflammation and loss of skeletal muscle mass in mice. Male BALB/c mice were exposed to 4 cigarettes/day, 6 days/week for 7 weeks, or sham handled. Mice consumed either standard laboratory chow (3.5 kcal/g, 12% fat) or a high fat diet (HFD, 4.3 kcal/g, 32% fat). Mice exposed to cigarette smoke for 7 weeks had significantly more inflammatory cells in the BALF (P<0.05) and the mRNA expression of proinflammatory cytokines and chemokines was significantly increased (P<0.05); HFD had no effect on these parameters. Sham- and smoke-exposed mice consuming the HFD were significantly heavier than chow fed animals (12 and 13%, respectively; P<0.05). Conversely, chow and HFD fed mice exposed to cigarette smoke weighed 16 and 15% less, respectively, compared to sham animals (P<0.05). The skeletal muscles (soleus, tibialis anterior and gastrocnemius) of cigarette smoke-exposed mice weighed significantly less than sham-exposed mice (P<0.05) and the HFD had no protective effect. For the first time we report that cigarette smoke exposure significantly decreased insulin-like growth factor-1 (IGF-1) mRNA expression in the gastrocnemius and tibialis anterior and IGF-1 protein in the gastrocnemius (P<0.05). We have also shown that cigarette smoke exposure reduced circulating IGF-1 levels. IL-6 mRNA expression was significantly elevated in all three skeletal muscles of chow fed smoke-exposed mice (P<0.05). In conclusion, these findings suggest that a downregulation in local IGF-1 may be responsible for the loss of skeletal muscle mass following cigarette smoke exposure in mice. © 2013 Hansen et al

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

A survey of psychological practitioner workplace wellbeing

The well-being of the psychological workforce is an area of concern. However, it has been sparsely studied in a holistic manner encompassing workplace well-being as well as burnout. This study reports a survey of 1,678 psychological practitioners accessed through professional networks. The short Warwick Edinburgh Mental Well-being Scale (SWEMWBS) and the Psychological Practitioner Workplace Well-being Measure (PPWWM) were administered with a demographic questionnaire. The mean for the SWEMWBS was below that of a national population survey. The intercorrelation of these tests was .61. Subgroup analyses showed significant differences: assistant psychologists, counsellors and psychological well-being practitioners demonstrated better than average workplace well-being. But for general well-being (SWEMWBS), trainee clinical psychologists and assistant psychologists showed lower than average well-being, whereas psychological well-being practitioners were higher than average. Other factors associated with well-being were contract type—both measures (higher workplace well-being in those with temporary contracts and the self-employed); employment sector—for PPWWM only (private organisation/independent workers and third sector/charitable organisation workers scored above the PPWWM mean); ethnicity—for both measures (Asian groups except Chinese had higher well-being than average for the PPWWM and SWEMWBS) and disability was strongly associated with lower well-being on both measures. Harassment, feeling depressed or a failure and wanting to leave the National Health Service (NHS) were associated with lower well-being. Greater age, pay and years of service were negatively correlated with well-being. A five-factor structure was obtained with this sample. The results confirmed psychological practitioners as an at-risk group and identified a number of factors associated with workplace well-being

Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD

Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base

Sequestration of Martian CO2 by mineral carbonation

Carbonation is the water-mediated replacement of silicate minerals, such as olivine, by carbonate, and is commonplace in the Earth’s crust. This reaction can remove significant quantities of CO2 from the atmosphere and store it over geological timescales. Here we present the first direct evidence for CO2 sequestration and storage on Mars by mineral carbonation. Electron beam imaging and analysis show that olivine and a plagioclase feldspar-rich mesostasis in the Lafayette meteorite have been replaced by carbonate. The susceptibility of olivine to replacement was enhanced by the presence of smectite veins along which CO2-rich fluids gained access to grain interiors. Lafayette was partially carbonated during the Amazonian, when liquid water was available intermittently and atmospheric CO2 concentrations were close to their present-day values. Earlier in Mars’ history, when the planet had a much thicker atmosphere and an active hydrosphere, carbonation is likely to have been an effective mechanism for sequestration of CO2

Evaluating methods for the analysis of rare variants in sequence data

A number of rare variant statistical methods have been proposed for analysis of the impending wave of next-generation sequencing data. To date, there are few direct comparisons of these methods on real sequence data. Furthermore, there is a strong need for practical advice on the proper analytic strategies for rare variant analysis. We compare four recently proposed rare variant methods (combined multivariate and collapsing, weighted sum, proportion regression, and cumulative minor allele test) on simulated phenotype and next-generation sequencing data as part of Genetic Analysis Workshop 17. Overall, we find that all analyzed methods have serious practical limitations on identifying causal genes. Specifically, no method has more than a 5% true discovery rate (percentage of truly causal genes among all those identified as significantly associated with the phenotype). Further exploration shows that all methods suffer from inflated false-positive error rates (chance that a noncausal gene will be identified as associated with the phenotype) because of population stratification and gametic phase disequilibrium between noncausal SNPs and causal SNPs. Furthermore, observed true-positive rates (chance that a truly causal gene will be identified as significantly associated with the phenotype) for each of the four methods was very low (<19%). The combination of larger than anticipated false-positive rates, low true-positive rates, and only about 1% of all genes being causal yields poor discriminatory ability for all four methods. Gametic phase disequilibrium and population stratification are important areas for further research in the analysis of rare variant data