Serious, Minor, and Non-Delinquents in Early Adolescence: The Impact of Cumulative Risk and Promotive Factors. The TRAILS Study

This study uses a social-ecological approach to the development of delinquency. The authors emphasize that a balance between eliminating risk and enhancing protection across domains is essential in reducing problems and promoting competence. The cumulative risk and promotive effects of temperament, family and school factors in preadolescence were examined on different groups of delinquents (based on self-report) in early adolescence. Data from the first two waves of the TRAILS study (N = 2,230) were used. The results provide evidence for a compensatory model that assumes main effects of risk and promotive factors on problem behavior. Accumulation of risks in preadolescence promoted being a serious delinquent in early adolescence, with the strongest effects for temperament. Accumulation of promotive effects decreased being a delinquent and supported being a non-delinquent. Furthermore, evidence is found for a counter-balancing effect of cumulative promotive and risk factors. Exposure to more promotive domains in the relative absence of risk domains decreased the percentage of serious delinquents. Our results did not support a protective model. Implications for prevention and intervention are discussed

A large-scale meta-analysis to refine colorectal cancer risk estimates associated with MUTYH variants

Background: defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance risk alleles. We report a large collaborative meta-analysis to assess and refine CRC risk estimates associated with bi-allelic and mono-allelic MUTYH variants and investigate age and sex influence on risk. Methods: MUTYH genotype data were included from 20 565 cases and 15 524 controls. Three logistic regression models were tested: a crude model; adjusted for age and sex; adjusted for age, sex and study. Results: all three models produced very similar results. MUTYH bi-allelic carriers demonstrated a 28-fold increase in risk (95% confidence interval (CI): 6.95-115). Significant bi-allelic effects were also observed for G396D and Y179C/G396D compound heterozygotes and a marginal mono-allelic effect for variant Y179C (odds ratio (OR)=1.34; 95% CI: 1.00-1.80). A pooled meta-analysis of all published and unpublished datasets submitted showed bi-allelic effects for MUTYH, G396D and Y179C (OR=10.8, 95% CI: 5.02-23.2; OR=6.47, 95% CI: 2.33-18.0; OR=3.35, 95% CI: 1.14-9.89) and marginal mono-allelic effect for variants MUTYH (OR=1.16, 95% CI: 1.00-1.34) and Y179C alone (OR=1.34, 95% CI: 1.01-1.77). Conclusions: overall, this large study refines estimates of disease risk associated with mono-allelic and bi-allelic MUTYH carriers

Methods for conducting systematic reviews of risk factors in low- and middle-income countries.

BACKGROUND: Rates of youth violence are disproportionately high in many low- and middle-income countries [LMICs] but existing reviews of risk factors focus almost exclusively on high-income countries. Different search strategies, including non-English language searches, might be required to identify relevant evidence in LMICs. This paper discusses methodological issues in systematic reviews aiming to include evidence from LMICs, using the example of a recent review of risk factors for child conduct problems and youth violence in LMICs. METHODS: We searched the main international databases, such as PsycINFO, Medline and EMBASE in English, as well as 12 regional databases in Arabic, Chinese, English, French, Spanish, Portuguese and Russian. In addition, we used internet search engines and Google Scholar, and contacted over 200 researchers and organizations to identify potentially eligible studies in LMICs. RESULTS: The majority of relevant studies were identified in the mainstream databases, but additional studies were also found through regional databases, such as CNKI, Wangfang, LILACS and SciELO. Overall, 85% of eligible studies were in English, and 15% were reported in Chinese, Spanish, Portuguese, Russian or French. Among eligible studies in languages other than English, two-thirds were identified only by regional databases and one-third was also indexed in the main international databases. CONCLUSIONS: There are many studies on child conduct problems and youth violence in LMICs which have not been included in prior reviews. Most research on these subjects in LMICs has been produced in the last two-three decades and mostly in middle-income countries, such as China, Brazil, Turkey, South Africa and Russia. Based on our findings, it appears that many studies of child conduct problems and youth violence in LMICs are reported in English, Chinese, Spanish and Portuguese, but few such studies are published in French, Arabic or Russian. If non-English language searches and screening had not been conducted in the current review, 15% of eligible studies would have been missed. Although there are benefits to non-English language searches and the inclusion of non-English studies in meta-analyses, systematic reviewers also need to consider the resources required to incorporate multi-lingual research.We are grateful to the Wellcome Trust [089963/Z/09/Z] and Bernard van Leer Foundation for financial support for the research

Statistical Methods in Recent HIV Noninferiority Trials: Reanalysis of 11 Trials

Background: In recent years the ‘‘noninferiority’ ’ trial has emerged as the new standard design for HIV drug development among antiretroviral patients often with a primary endpoint based on the difference in success rates between the two treatment groups. Different statistical methods have been introduced to provide confidence intervals for that difference. The main objective is to investigate whether the choice of the statistical method changes the conclusion of the trials. Methods: We presented 11 trials published in 2010 using a difference in proportions as the primary endpoint. In these trials, 5 different statistical methods have been used to estimate such confidence intervals. The five methods are described and applied to data from the 11 trials. The noninferiority of the new treatment is not demonstrated if the prespecified noninferiority margin it includes in the confidence interval of the treatment difference. Results: Results indicated that confidence intervals can be quite different according to the method used. In many situations, however, conclusions of the trials are not altered because point estimates of the treatment difference were too far from the prespecified noninferiority margins. Nevertheless, in few trials the use of different statistical methods led to different conclusions. In particular the use of ‘‘exact’ ’ methods can be very confusing. Conclusion: Statistical methods used to estimate confidence intervals in noninferiority trials have a strong impact on th

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page