The Effects of Different Aspirin Dosing Frequencies and the Timing of Aspirin Intake in Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review.

Enhancing the effectiveness of aspirin by tailoring administration regimens is an important question among health professionals. We conducted a systematic review to evaluate the evidence on the effects of different aspirin regimens in terms of timing (chronotherapy) or frequency of dosing in the prevention of cardiovascular disease. Only two out of the 28 included studies reported long-term cardiovascular outcomes, highlighting an evidence gap that future research should address. The remaining 26 studies used surrogate outcomes.

Use of next-generation sequencing and candidate gene analysis to identify underlying defects in patients with inherited platelet function disorders.

BACKGROUND: Inherited platelet function disorders (PFDs) are heterogeneous, and identification of the underlying genetic defects is difficult when based solely on phenotypic and clinical features of the patient. OBJECTIVE: To analyze 329 genes regulating platelet function, number, and size in order to identify candidate gene defects in patients with PFDs. PATIENTS/METHODS: Targeted analysis of candidate PFD genes was undertaken after next-generation sequencing of exomic DNA from 18 unrelated index cases with PFDs who were recruited into the UK Genotyping and Phenotyping of Platelets (GAPP) study and diagnosed with platelet abnormalities affecting either Gi signaling (n = 12) or secretion (n = 6). The potential pathogenicity of candidate gene defects was assessed using computational predictive algorithms. RESULTS: Analysis of the 329 candidate PFD genes identified 63 candidate defects, affecting 40 genes, among index cases with Gi signaling abnormalities, while 53 defects, within 49 genes, were identified among patients with secretion abnormalities. Homozygous gene defects were more commonly associated with secretion abnormalities. Functional annotation analysis identified distinct gene clusters in the two patient subgroups. Thirteen genes with significant annotation enrichment for 'intracellular signaling' harbored 16 of the candidate gene defects identified in nine index cases with Gi signaling abnormalities. Four gene clusters, representing 14 genes, with significantly associated gene ontology annotations were identified among the cases with secretion abnormalities, the most significant association being with 'establishment of protein localization.' CONCLUSION: Our findings demonstrate the genetic complexity of PFDs and highlight plausible candidate genes for targeted analysis in patients with platelet secretion and Gi signaling abnormalities.

Exotic becomes erotic: interpreting the biological correlates of sexual orientation.

Although biological findings currently dominate the research literature on the determinants of sexual orientation, biological theorizing has not yet spelled out a developmental path by which any of the various biological correlates so far identified might lead to a particular sexual orientation. The Exotic-Becomes-Erotic (EBE) theory of sexual orientation (Bem, 1996) attempts to do just that, by suggesting how biological variables might interact with experiential and sociocultural factors to influence an individual's sexual orientation. Evidence for the theory is reviewed, and a path analysis of data from a large sample of twins is presented which yields preliminary support for the theory's claim that correlations between genetic variables and sexual orientation are mediated by childhood gender nonconformity.

Is EBE theory supported by the evidence? Is it androcentric? A reply to Peplau et al. (1998)

In their critique of the author's Exotic-Becomes-Erotic (EBE) theory of sexual orientation (D. J. Bem, 1996), L. A. Peplau, L. D. Garnets, L. R. Spalding, T. D. Conley, and R. C. Veniegas (1998) challenge his reading of the evidence concerning the antecedents of sexual orientation; they also contend that the theory neglects women's experiences. In reply, the author argues that L. A. Peplau et al. have misunderstood the critical antecedent variable of the theory and, hence, have misidentified the particular empirical findings that would serve to confirm or disconfirm its central contentions. The author also argues that the sex differences they cite are not relevant to the theory, whereas an important sex difference they do not cite is actually anticipated by it.

Continuities and consequences of interactional styles across the life course.

Behavior patterns can be sustained across the life course by two kinds of person-environment interaction. Cumulative continuity arises when an individual's interactional style channels him or her into environments that themselves reinforce that style, thereby sustaining the behavior pattern across the life course through the progressive accumulation of its own consequences. Interactional continuity arises when an individual's style evokes reciprocal, sustaining responses from others in ongoing social interaction, thereby reinstating the behavior pattern across the individual's life course whenever the relevant interactive situation is replicated. Using archival data from the Berkeley Guidance Study (Macfarlane, Allen, & Honzik, 1954), we present evidence for the operation of these two continuity-promoting processes by identifying individuals who were ill-tempered, shy, or dependent in late childhood and then tracing the continuities and consequences of these interactional styles across the subsequent 30 years of their lives in the domains of work and family. The importance of the sociocultural context in mediating these continuities and consequences is stressed.