Comparison of Pattern Detection Methods in Microarray Time Series of the Segmentation Clock

While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis. A method related to Fourier analysis, the Lomb-Scargle periodogram, was used to detect periodic profiles in the dataset, leading to the identification of a novel set of cyclic genes associated with the segmentation clock. Here, we applied to the same microarray time series dataset four distinct mathematical methods to identify significant patterns in gene expression profiles. These methods are called: Phase consistency, Address reduction, Cyclohedron test and Stable persistence, and are based on different conceptual frameworks that are either hypothesis- or data-driven. Some of the methods, unlike Fourier transforms, are not dependent on the assumption of periodicity of the pattern of interest. Remarkably, these methods identified blindly the expression profiles of known cyclic genes as the most significant patterns in the dataset. Many candidate genes predicted by more than one approach appeared to be true positive cyclic genes and will be of particular interest for future research. In addition, these methods predicted novel candidate cyclic genes that were consistent with previous biological knowledge and experimental validation in mouse embryos. Our results demonstrate the utility of these novel pattern detection strategies, notably for detection of periodic profiles, and suggest that combining several distinct mathematical approaches to analyze microarray datasets is a valuable strategy for identifying genes that exhibit novel, interesting transcriptional patterns

Effectiveness of psychoeducational interventions for family carers of people with psychosis: A systematic review and meta-analysis.

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52weeks, and contact times ranged from 6 to 42hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI -0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD -0.230, 95% CI -0.386 to -0.075), perceived burden (SMD -0.434, 95% CI -0.567 to -0.31), negative caregiving experiences (SMD -0.210, 95% CI -0.396 to -0.025) and expressed emotion (SMD -0.161, 95% CI -0.367 to -0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

Effectiveness of psychoeducational interventions for family carers of people

Psychoeducational interventions for family carers of people with psychosis are effective for improving compliance and preventing relapse. Whether carers benefit from these interventions has been little explored. This systematic review investigated the effectiveness of psychoeducation for improving carers' outcomes, and potential treatment moderators. We searched for randomised controlled trials (RCTs) published in English or Chinese in eight databases. Carers' outcomes included wellbeing, quality of life, global morbidities, burden, and expressed emotion. Thirty-two RCTs were included, examining 2858 carers. Intervention duration ranged from 4 to 52 weeks, and contact times ranged from 6 to 42 hours. At post intervention, findings were equivocal for carers' wellbeing (SMD 0.103, 95% CI − 0.186 to 0.392). Conversely, psychoeducation was superior in reducing carers' global morbidities (SMD − 0.230, 95% CI − 0.386 to − 0.075), perceived burden (SMD − 0.434, 95% CI − 0.567 to − 0.31), negative caregiving experiences (SMD − 0.210, 95% CI − 0.396 to − 0.025) and expressed emotion (SMD − 0.161, 95% CI − 0.367 to − 0.045). The lack of available data precluded meta-analysis of outcomes beyond short-term follow-up. Meta-regression revealed no significant associations between intervention modality, duration, or contact time and outcomes. Further research should focus on improving carers' outcomes in the longer-term and identifying factors to optimise intervention design

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A microcomputer graphics package for use with a high-resolution raster-scan dot-matrix printer

Typescript (photocopy).Digitized by Kansas Correctional Industrie