Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased

Comparative Lipidomics in Clinical Isolates of Candida albicans Reveal Crosstalk between Mitochondria, Cell Wall Integrity and Azole Resistance

Prolonged usage of antifungal azoles which target enzymes involved in lipid biosynthesis invariably leads to the development of multi-drug resistance (MDR) in Candida albicans. We had earlier shown that membrane lipids and their fluidity are closely linked to the MDR phenomenon. In one of our recent studies involving comparative lipidomics between azole susceptible (AS) and azole resistant (AR) matched pair clinical isolates of C. albicans, we could not see consistent differences in the lipid profiles of AS and AR strains because they came from different patients and so in this study, we have used genetically related variant recovered from the same patient collected over a period of 2-years. During this time, the levels of fluconazole (FLC) resistance of the strain increased by over 200-fold. By comparing the lipid profiles of select isolates, we were able to observe gradual and statistically significant changes in several lipid classes, particularly in plasma membrane microdomain specific lipids such as mannosylinositolphosphorylceramides and ergosterol, and in a mitochondrial specific phosphoglyceride, phosphatidyl glycerol. Superimposed with these quantitative and qualitative changes in the lipid profiles, were simultaneous changes at the molecular lipid species levels which again coincided with the development of resistance to FLC. Reverse transcriptase-PCR of the key genes of the lipid metabolism validated lipidomic picture. Taken together, this study illustrates how the gradual corrective changes in Candida lipidome correspond to the development of FLC tolerance. Our study also shows a first instance of the mitochondrial membrane dysfunction and defective cell wall (CW) in clinical AR isolates of C. albicans, and provides evidence of a cross-talk between mitochondrial lipid homeostasis, CW integrity and azole tolerance

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

Roadmap on dynamics of molecules and clusters in the gas phase

This roadmap article highlights recent advances, challenges and future prospects in studies of the dynamics of molecules and clusters in the gas phase. It comprises nineteen contributions by scientists with leading expertise in complementary experimental and theoretical techniques to probe the dynamics on timescales spanning twenty order of magnitudes, from attoseconds to minutes and beyond, and for systems ranging in complexity from the smallest (diatomic) molecules to clusters and nanoparticles. Combining some of these techniques opens up new avenues to unravel hitherto unexplored reaction pathways and mechanisms, and to establish their significance in, e.g. radiotherapy and radiation damage on the nanoscale, astrophysics, astrochemistry and atmospheric science

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Not AvailableSoil fertility and yield on sustainable basis may improve by conservation tillage and nitrogen management. This study was aim to appraise impact of 3 tillage viz. zero (ZT), reduced (RT) and conventional tillage (CT) without or with residue retention/incorporation and 5 N rates (0, 80, 120, 160, and 200 kg·N·ha-1) on yield, grain quality and soil health i.e. soil organic matter (SOC), bulk density, infiltration rate and microbial biomass carbon of wheat. Nitrogen rates was significantly exaggerated yield and quality where highest values recorded at 200 kg·N·ha-1. Mean maximum grain yield (46.13 and 47.18 q ha-1 and protein % 11.1 to 12.1%, gluten 10.6% and starch 63.5 to 67.5%) could be attained at 160 kg·N·ha-1. The use of ZT with residue retention and RT with residue retention for two crop cycle increased soil organic carbon by 54.68% and 54.22% more than that of conventional tillage (CT), respectively. The SOC, WSOC, POC and MBC were highest under ZT as against reduced (RT) and conventional tillage (CT). Nevertheless, tillage × N interactions were not significant for most of the parameters under this study, the general influence of ZT with 160 kg·N·ha-1 on sandy loam soil seemed to be most positive than RT and CT. Thus, results advise that ZT with 160 kg·N·ha-1 was finest and sustainable approach to attain more yield and also to improve SOC and MBC of subtropical IndiaNot Availabl

Not Available

Not AvailableSoil fertility and yield on sustainable basis may improve by conservation tillage and nitrogen management. This study was aim to appraise impact of 3 tillage viz. zero (ZT), reduced (RT) and conventional tillage (CT) without or with residue retention/incorporation and 5 N rates (0, 80, 120, 160, and 200 kg·N·ha-1) on yield, grain quality and soil health i.e. soil organic matter (SOC), bulk density, infiltration rate and microbial biomass carbon of wheat. Nitrogen rates was significantly exaggerated yield and quality where highest values recorded at 200 kg·N·ha-1. Mean maximum grain yield (46.13 and 47.18 q ha-1 and protein % 11.1 to 12.1%, gluten 10.6% and starch 63.5 to 67.5%) could be attained at 160 kg·N·ha-1. The use of ZT with residue retention and RT with residue retention for two crop cycle increased soil organic carbon by 54.68% and 54.22% more than that of conventional tillage (CT), respectively. The SOC, WSOC, POC and MBC were highest under ZT as against reduced (RT) and conventional tillage (CT). Nevertheless, tillage × N interactions were not significant for most of the parameters under this study, the general influence of ZT with 160 kg·N·ha-1 on sandy loam soil seemed to be most positive than RT and CT. Thus, results advise that ZT with 160 kg·N·ha-1 was finest and sustainable approach to attain more yield and also to improve SOC and MBC of subtropical IndiaNot Availabl