A Comparison of Different Approaches to Unravel the Latent Structure within Metabolic Syndrome

Background: Exploratory factor analysis is a commonly used statistical technique in metabolic syndrome research to uncover latent structure amongst metabolic variables. The application of factor analysis requires methodological decisions that reflect the hypothesis of the metabolic syndrome construct. These decisions often raise the complexity of the interpretation from the output. We propose two alternative techniques developed from cluster analysis which can achieve a clinically relevant structure, whilst maintaining intuitive advantages of clustering methodology. Methods: Two advanced techniques of clustering in the VARCLUS and matroid methods are discussed and implemented on a metabolic syndrome data set to analyze the structure of ten metabolic risk factors. The subjects were selected from the normative aging study based in Boston, Massachusetts. The sample included a total of 847 men aged between 21 and 81 years who provided complete data on selected risk factors during the period 1987 to 1991. Results: Four core components were identified by the clustering methods. These are labelled obesity, lipids, insulin resistance and blood pressure. The exploratory factor analysis with oblique rotation suggested an overlap of the loadings identified on the insulin resistance and obesity factors. The VARCLUS and matroid analyses separated these components and were able to demonstrate associations between individual risk factors. Conclusions: An oblique rotation can be selected to reflect the clinical concept of a single underlying syndrome, howeve

Development and evaluation of an intervention providing insight into the tobacco industry to prevent smoking uptake: a mixed-methods study

Background Smokers who start smoking at an early age are less likely to quit and more likely to die from their habit. Evidence from the US Truth® campaign suggests that interventions focusing on tobacco industry practices and ethics may be effective in preventing smoking uptake. Objectives In an exploratory study, to develop, pilot and provide preliminary evidence of the acceptability and effectiveness of Operation Smoke Storm, a school-based intervention based on the premise of the Truth® campaign, to prevent smoking uptake. Design Mixed-methods, non-randomised controlled study. Component 1 was delivered to Year 7 students, and student focus groups and teacher interviews were conducted to refine the lessons and to develop components 2 and 3. The revised Year 7 lessons and accompanying family booklet were delivered to new Year 7 students 1 year later in one school only; Year 8 students in both schools received the booster session. Setting and participants Students in Years 7–8 (aged 11–13 years) in two UK schools. Intervention A three-component intervention comprising (1) three 50-minute classroom-based sessions in Year 7 in which students acted as secret agents to uncover industry practices through videos, quizzes, discussions and presentations; (2) an accompanying family booklet containing activities designed to stimulate discussions about smoking between parents and students; and (3) a 1-hour interactive classroom-based booster session for Year 8 students, in which students learnt about tobacco marketing strategies from the perspectives of an industry executive, a marketing company and a health campaigner. Main outcome measures Odds ratios to compare the self-reported prevalence of ever smoking and susceptibility to smoking in Year 8 students after the delivery of the booster session in study schools compared with students in local control schools. Qualitative data on acceptability of the intervention. Results The combined prevalence of ever smoking and susceptibility increased from 18.2% in Year 7 to 33.8% in Year 8. After adjusting for confounders there was no significant difference in the odds of a Year 8 student in an intervention school being an ever smoker or susceptible never smoker compared with controls [adjusted odds ratio (aOR) 1.28, 95% confidence interval (CI) 0.83 to 1.97; p = 0.263] and no significant difference in the odds of ever smoking (aOR 0.82, 95% CI 0.42 to 1.58; p = 0.549). Students mostly enjoyed the intervention and acquired new knowledge that appeared to strengthen their aversion to smoking. Teachers liked the ‘off-the-shelf’ nature of the resource, although they highlighted differences by academic ability in the extent to which students understood the messages being presented. Use of the family component was low but it was received positively by those parents who did engage with it. Limitations Logistical difficulties meant that students’ responses in Year 7 and Year 8 could not be linked; however, baseline smoking behaviours differed little between intervention and control schools, and analyses were adjusted for confounders measured at follow-up. Conclusions Operation Smoke Storm is an acceptable resource for delivering smoking-prevention education but it does not appear to have reduced smoking and susceptibility. Future work The lack of a strong signal for potential effectiveness, considered alongside logistical difficulties in recruiting and working with schools, suggests that a fully powered cluster randomised trial of the intervention is not warranted

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.

The acidity of atmospheric particles and clouds

202307 bcchVersion of RecordRGCOthersExcellent Science; PANACEA; National Science Foundation; U.S. Department of Energy; U.S. Environmental Protection Agency; Office of Science; Natural Sciences and Engineering Research Council of Canada; European Commission; European Research Council; European Regional Development FundPublishe

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function

Prediction of wheat response to an application of phosphorus under field conditions using diffusive gradients in thin-films (DGT) and extraction methods

The ability of the Diffusive Gradients in Thin Films (DGT) technique and two other established testing methods (Colwell, resin) to predict wheat responsiveness to applied P from 35 field trials across southern Australia was investigated. Regression analysis of relative early dry matter production and grain yield responses demonstrated that the DGT method predicted plant responsiveness to applied P more accurately than Colwell P and resin P at sites where maximum yields were reached with P rates used (20 out of 35). The measured concentration in soils at the DGT surface, C-DGT, explained 74% of the variation in response for both early dry matter and grain, compared to 7% for early dry matter and 35% for grain using the resin P method. No significant relationships could be obtained for Colwell P although modifying the Colwell test data using Phosphorus Buffering Index resulted in a correct response prediction for 11 of the 20 field sites compared to 18 for DGT and 14 for resin P. These observations suggest that the DGT technique can assess plant available P in soils with significantly greater accuracy than traditional soil P testing methods. The critical P threshold, expressed as C-DGT, was 255 mu g L-1 for early dry matter and 66 mu g L-1 for grain