Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data

In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).

Multiplicity of data in trial reports and the reliability of meta-analyses: empirical study

Objectives To examine the extent of multiplicity of data in trial reports and to assess the impact of multiplicity on meta-analysis results. Design Empirical study on a cohort of Cochrane systematic reviews. Data sources All Cochrane systematic reviews published from issue 3 in 2006 to issue 2 in 2007 that presented a result as a standardised mean difference (SMD). We retrieved trial reports contributing to the first SMD result in each review, and downloaded review protocols. We used these SMDs to identify a specific outcome for each meta-analysis from its protocol. Review methods Reviews were eligible if SMD results were based on two to ten randomised trials and if protocols described the outcome. We excluded reviews if they only presented results of subgroup analyses. Based on review protocols and index outcomes, two observers independently extracted the data necessary to calculate SMDs from the original trial reports for any intervention group, time point, or outcome measure compatible with the protocol. From the extracted data, we used Monte Carlo simulations to calculate all possible SMDs for every meta-analysis. Results We identified 19 eligible meta-analyses (including 83 trials). Published review protocols often lacked information about which data to choose. Twenty-four (29%) trials reported data for multiple intervention groups, 30 (36%) reported data for multiple time points, and 29 (35%) reported the index outcome measured on multiple scales. In 18 meta-analyses, we found multiplicity of data in at least one trial report; the median difference between the smallest and largest SMD results within a meta-analysis was 0.40 standard deviation units (range 0.04 to 0.91). Conclusions Multiplicity of data can affect the findings of systematic reviews and meta-analyses. To reduce the risk of bias, reviews and meta-analyses should comply with prespecified protocols that clearly identify time points, intervention groups, and scales of interest.

Insights into the timing of repeated testing after treatment for Chlamydia trachomatis: data and modelling study

The objective of this study was to determine the optimal time interval for a repeated Chlamydia trachomatis (chlamydia) test.

Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age

Stem cells of various tissues are typically defined as multipotent cells with 'self-renewal' properties. Despite the increasing interest in stem cells, surprisingly little is known about the number of times stem cells can or do divide over a lifetime. Based on telomere-length measurements of hematopoietic cells, we previously proposed that the self-renewal capacity of hematopoietic stem cells is limited by progressive telomere attrition and that such cells divide very rapidly during the first year of life. Recent studies of patients with aplastic anemia resulting from inherited mutations in telomerase genes support the notion that the replicative potential of hematopoietic stem cells is directly related to telomere length, which is indirectly related to telomerase levels. To revisit conclusions about stem cell turnover based on cross-sectional studies of telomere length, we performed a longitudinal study of telomere length in leukocytes from newborn baboons. All four individual animals studied showed a rapid decline in telomere length (approximately 2-3 kb) in granulocytes and lymphocytes in the first year after birth. After 50-70 weeks the telomere length appeared to stabilize in all cell types. These observations suggest that hematopoietic stem cells, after an initial phase of rapid expansion, switch at around 1 year of age to a different functional mode characterized by a markedly decreased turnover rate.

Waiting times for cataract surgery in ten European countries: an analysis using data from the SHARE survey

AIMS: To assess waiting times for cataract surgery and their acceptance in European countries, and to find explanatory, country-specific health indicators. METHODS: Using data from the survey of health, ageing and retirement in Europe (SHARE), waiting times for cataract surgery of 245 respondents in ten countries were analysed with the help of linear regression. The influence of four country specific health indicators on waiting times was studied by multiple linear regression. The influence of waiting time and country on the wish to have surgery performed earlier was determined through logistic regression. Additional information was obtained for each country from opinion leaders in the field of cataract surgery. RESULTS: Waiting times differed significantly (p<0.001) between the ten analysed European countries. The length of wait was significantly influenced by the total expenditure on health (p<0.01) but not by the other country specific health indicators. The wish to have surgery performed earlier was determined by the length of wait (p<0.001) but not by the country where surgery was performed. CONCLUSION: The length of wait is influenced by the total expenditure on health, but not by the rate of public expenditure on health, by the physician density or by the acute bed density. The wish to have surgery performed earlier depends on the length of wait for surgery and is not influenced by the country.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Ragu: a free tool for the analysis of EEG and MEG event-related scalp field data using global randomization statistics

We present a program (Ragu; Randomization Graphical User interface) for statistical analyses of multichannel event-related EEG and MEG experiments. Based on measures of scalp field differences including all sensors, and using powerful, assumption-free randomization statistics, the program yields robust, physiologically meaningful conclusions based on the entire, untransformed, and unbiased set of measurements. Ragu accommodates up to two within-subject factors and one between-subject factor with multiple levels each. Significance is computed as function of time and can be controlled for type II errors with overall analyses. Results are displayed in an intuitive visual interface that allows further exploration of the findings. A sample analysis of an ERP experiment illustrates the different possibilities offered by Ragu. The aim of Ragu is to maximize statistical power while minimizing the need for a-priori choices of models and parameters (like inverse models or sensors of interest) that interact with and bias statistics.

Role of diuretics, blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

OBJECTIVE To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. DESIGN Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. SETTING NAVIGATOR trial. PARTICIPANTS Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. MAIN OUTCOME MEASURES Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. RESULTS During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). CONCLUSIONS Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.

Streaming Support for Data Intensive Cloud-Based Sequence Analysis

Cloud computing provides a promising solution to the genomics data deluge problem resulting from the advent of next-generation sequencing (NGS) technology. Based on the concepts of “resources-on-demand” and “pay-as-you-go”, scientists with no or limited infrastructure can have access to scalable and cost-effective computational resources. However, the large size of NGS data causes a significant data transfer latency from the client’s site to the cloud, which presents a bottleneck for using cloud computing services. In this paper, we provide a streaming-based scheme to overcome this problem, where the NGS data is processed while being transferred to the cloud. Our scheme targets the wide class of NGS data analysis tasks, where the NGS sequences can be processed independently from one another. We also provide the elastream package that supports the use of this scheme with individual analysis programs or with workflow systems. Experiments presented in this paper show that our solution mitigates the effect of data transfer latency and saves both time and cost of computation.