Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research

Selenium Treatment and Chagasic Cardiopathy (STCC): study protocol for a double-blind randomized controlled trial

Background: Heart disease progression occurs in 30% of patients with chronic Trypanosoma cruzi infection. Supplementation with selenium (Se) in animal model of T. cruzi infection produced promising results. There is evidence that patients with Chagas heart disease have lower Se levels than healthy individuals and patients with T. cruzi infection without of cardiac disease. The aim of this investigation is to estimate the effect of Se treatment on prevention of heart disease progression in patients with chagasic cardiopathy. Methods: The Selenium Treatment and Chagasic Cardiopathy trial is a superiority, double-blind, placebo-controlled, randomized clinical trial. The eligibility criteria are as follows: (1) a Chagas disease diagnosis confirmed by serology; (2) segmental, mild or moderate global left ventricular systolic dysfunction; and (3) age between 18 and 65 years. The exclusion criteria are as follows: (1) pregnancy, (2) diabetes mellitus, (3) tobacco use, (4) alcohol abuse, (5) evidence of nonchagasic heart disease, (6) depression, (7) dysphagia with evidence of food residues in the esophagus, (8) dysphagia with weight loss higher than 15% of usual weight in the last four months and/or (9) conditions that may result in low protocol adherence. The intervention will be 100 μg of sodium selenite once daily for 365 consecutive days compared to placebo. The following are the primary outcomes to be measured: (1) the trajectories of the left ventricular ejection fraction in the follow-up period; (2) reduction of heart disease progression rates, with progression defined as a 10% decrease in left ventricular ejection fraction; and (3) rate of hospital admissions attributable to dysrhythmia, heart failure or stroke due to Chagas disease. One hundred thirty patients will be randomly allocated into either the intervention or placebo group at a ratio of 1:1. The sequence allocation concealment and blinding were planned to be conducted with the strategy of numbered boxes. Both patients and health-care providers will remain blinded to the intervention groups during the 5 years of follow-up. Discussion: If Se treatment reduces the progression of Chagas cardiopathy, the inclusion of this micronutrient in the daily diet can improve the therapeutic regimen for this neglected tropical disease at low cost

Developing professional competencies for humanitarian engineers

One of the roles of engineering institutions is the registration and regulation of engineering professionals, assessing their competence in both technical and management areas. A similar approach is being promoted for professional humanitarian engineers, identifying core competencies relevant to emergency relief work. This would improve standards in the workforce, allow training and experience to be independently evaluated, and facilitate the careers of people working in a very mobile sector. Using the experiences of RedR UK in recruiting and training humanitarian engineers, this paper explores the skills, knowledge and other attributes that distinguish an enthusiastic but ill-informed and inexperienced person from somebody with the expertise to work efficiently, effectively and ethically in a challenging humanitarian context

Changing governance structures and the evolution of Public Service Bargains in Hong Kong

postprin