Hydrogen inhalation ameliorates ventilator-induced lung injury

Introduction\ud Mechanical ventilation (MV) can provoke oxidative stress and an inflammatory response, and subsequently cause ventilator-induced lung injury (VILI), a major cause of mortality and morbidity of patients in the intensive care unit. Inhaled hydrogen can act as an antioxidant and may be useful as a novel therapeutic gas. We hypothesized that, owing to its antioxidant and anti-inflammatory properties, inhaled hydrogen therapy could ameliorate VILI.\ud \ud Methods\ud VILI was generated in male C57BL6 mice by performing a tracheostomy and placing the mice on a mechanical ventilator (tidal volume of 30 ml/kg without positive end-expiratory pressure, FiO2 0.21). The mice were randomly assigned to treatment groups and subjected to VILI with delivery of either 2% nitrogen or 2% hydrogen in air. Sham animals were given same gas treatments for two hours (n = 8 for each group). The effects of VILI induced by less invasive and longer exposure to MV (tidal volume of 10 ml/kg, 5 hours, FiO2 0.21) were also investigated (n = 6 for each group). Lung injury score, wet/dry ratio, arterial oxygen tension, oxidative injury, and expression of pro-inflammatory mediators and apoptotic genes were assessed at the endpoint of two hours using the high-tidal volume protocol. Gas exchange and apoptosis were assessed at the endpoint of five hours using the low-tidal volume protocol.\ud \ud Results\ud Ventilation (30 ml/kg) with 2% nitrogen in air for 2 hours resulted in deterioration of lung function, increased lung edema, and infiltration of inflammatory cells. In contrast, ventilation with 2% hydrogen in air significantly ameliorated these acute lung injuries. Hydrogen treatment significantly inhibited upregulation of the mRNAs for pro-inflammatory mediators and induced antiapoptotic genes. In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Similarly, longer exposure to mechanical ventilation within lower tidal volume (10 mg/kg, five hours) caused lung injury including bronchial epithelial apoptosis. Hydrogen improved gas exchange and reduced VILI-induced apoptosis.\ud \ud Conclusions\ud Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects

Rfit: Rank-based Estimation for Linear Models

and Jaeckel proposed rank estimation for linear models. Since that time, several authors have developed inference and diagnostic methods for these estimators. These rank-based estimators and their associated inference are highly efficient and are robust to outliers in response space. The methods include estimation of standard errors, tests of general linear hypotheses, confidence intervals, diagnostic procedures including stu-dentized residuals, and measures of influential cases. We have developed an R package, Rfit, for computing of these robust procedures. In this paper we highlight the main features of the pack-age. The package uses standard linear model syntax and includes many of the main inference and diagnostic functions

Rank-Based Analysis of Unbalanced Repeated Measures Data

In this article, we have developed a rank (intra-subject) based analysis of clinical trials with unbalanced repeated measures data. We assume that the errors within each patient are exchangeable and continuous random variables. This rank-based inference is valid when the unbalanced data are missing either completely at random or by design. A drop in dispersion test is developed for general linear hypotheses. A numerical example is given to illustrate the procedure

Human exposure to anopheline mosquitoes occurs primarily indoors, even for users of insecticide-treated nets in Luangwa Valley, South-east Zambia.

ABSTRACT: BACKGROUND: Current front line malaria vector control methods such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), rely upon the preference of many primary vectors to feed and/or rest inside human habitations where they can be targeted with domesticallyapplied insecticidal products. We studied the human biting behaviour of the malaria vector Anopheles funestus Giles and the potential malaria vector Anopheles quadriannulatus Theobald in Luangwa valley, south-east Zambia. METHODS: Mosquitoes were collected by human landing catch in blocks of houses with either combined use of deltamethrin-based IRS and LLINs or LLINs alone. Human behaviour data were collected to estimate how much exposure to mosquito bites indoors and outdoors occurred at various times of the night for LLIN users and non-users. RESULTS: Anopheles funestus and An. quadriannulatus did not show preference to bite either indoors or outdoors: the proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821] and 0.624 [0.324, 0.852], respectively. However, the overwhelming majority of both species were caught at times when most people are indoors. The proportion of mosquitoes caught at a time when most people are indoors were 0.981 [0.881, 0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human exposure to both species occuring indoors was high for individuals lacking LLINs (An. funestus: 0.983 and An. quadriannulatus: 0.970, respectively). While LLIN users were better protected, more than half of their exposure was nevertheless estimated to occur indoors (An. funestus: 0.570 and An. quadriannulatus: 0.584). CONCLUSIONS: The proportion of human exposure to both An. funestus and An. quadriannulatus occuring indoors was high in the area and hence both species might be responsive to further peridomestic measures if these mosquitoes are susceptible to insecticidal products