Exploring the relationship between childhood neglect and violence in a sample of high-risk early adolescents: findings from a longitudinal study

Introduction. Youth violence rates have increased more than adult rates since 2004. Child maltreatment is a key risk factor for violent behavior in youth. Although neglect is the most prevalent form of childhood maltreatment, its contribution to development of violence is unclear, as is the potential mediating role of social bonds. This dissertation assesses the relationship between childhood neglect before age 8 and the development of early adolescent violence (EAV) by age 14, and examines whether social bonds, defined according to Social Control Theory (SCT), mediate this relationship. Methods. Data came from interviews of children (n = 352) from two samples of the LONGSCAN (Longitudinal Studies of Child Abuse and Neglect) Consortium who completed the Conduct Disorder module of the Diagnostic Interview Schedule for Children-Version IV (DISC). The outcome was self-reported perpetration of serious violence in the previous 12 months. Additional data came from the child's caregivers and social service agency records. Data were analyzed to examine differences between violent and non-violent youths based on exposure to maltreatment. Negative binomial regression models assessed the neglect-EAV relationship by examining incidence rate ratios (IRR). Specific indirect effects were examined to determine whether the four SCT constructs (attachment, commitment, belief, involvement) mediated the neglect-EAV relationship. Results. Only 11% (n = 38) reported engagement in any EAV but nearly twice as many females (n = 2 4) than males (n = 14) reported EAV. The relationship between neglect and EAV was not significant (IRR = 1.04). Social bonds did not mediate the neglect-EAV relationship, although weaker commitment (B = -0.413; p < .05) and attachment (B = -0.385; p < 0.05) predicted higher EAV rates. However, there was a significant effect of peer criminality on the rate of EAV. Conclusion. Though limited by lack of statistical power, this study demonstrated that social bonds are influential on the perpetration of violence in early teens. Social bonds, however, do not appear to mediate the neglect-EAV relationship. Further testing of this conceptual framework and exploration of sex differences are warranted. Efforts to facilitate strong attachments to caregivers, prosocial peers, and institutions are worth considering as preventive strategies

Peer Reviewed Evaluation of Registered End-Points of Randomised Trials (the PRE-REPORT study): a stepped wedge, cluster-randomised trial.

OBJECTIVE: To test whether providing relevant clinical trial registry information to peer reviewers evaluating trial manuscripts decreases discrepancies between registered and published trial outcomes. DESIGN: Stepped wedge, cluster-randomised trial, with clusters comprised of eligible manuscripts submitted to each participating journal between 1 November 2018 and 31 October 2019. SETTING: Thirteen medical journals. PARTICIPANTS: Manuscripts were eligible for inclusion if they were submitted to a participating journal during the study period, presented results from the primary analysis of a clinical trial, and were peer reviewed. INTERVENTIONS: During the control phase, there were no changes to pre-existing peer review practices. After journals crossed over into the intervention phase, peer reviewers received a data sheet describing whether trials were registered, the initial registration and enrolment dates, and the registered primary outcome(s) when enrolment began. MAIN OUTCOME MEASURE: The presence of a clearly defined, prospectively registered primary outcome consistent with the primary outcome in the published trial manuscript, as determined by two independent outcome assessors. RESULTS: We included 419 manuscripts (243 control and 176 intervention). Participating journals published 43% of control-phase manuscripts and 39% of intervention-phase manuscripts (model-estimated percentage difference between intervention and control trials = -10%, 95% CI -25% to 4%). Among the 173 accepted trials, published primary outcomes were consistent with clearly defined, prospectively registered primary outcomes in 40 of 105 (38%) control-phase trials and 27 of 68 (40%) intervention-phase trials. A linear mixed model did not show evidence of a statistically significant primary outcome effect from the intervention (estimated difference between intervention and control=-6% (90% CI -27% to 15%); one-sided p value=0.68). CONCLUSIONS: These results do not support use of the tested intervention as implemented here to increase agreement between prospectively registered and published trial outcomes. Other approaches are needed to improve the quality of outcome reporting of clinical trials. TRIAL REGISTRATION NUMBER: ISRCTN41225307

A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis