Melissa D. Begg

Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study

Abstract Objective: To examine the relation between birth weight and measured intelligence at age 7 years in children within the normal range of birth weight and in siblings. Design: Cohort study of siblings of the same sex. Setting: 12 cities in the United States. Subjects: 3484 children of 1683 mothers in a birth cohort study during the years 1959 through 1966. The sample was restricted to children born at ≥37 weeks gestation and with birth weights of 1500-3999 g. Main outcome measure: Full scale IQ at age 7 years. Results: Mean IQ increased monotonically with birth weight in both sexes across the range of birth weight in a linear regression analysis of one randomly selected sibling per family (n= 1683) with adjustment for maternal age, race, education, socioeconomic status, and birth order. Within same sex sibling pairs, differences in birth weight were directly associated with differences in IQ in boys (812 pairs, predicted IQ difference per 100 g change in birth weight =0.50, 95% confidence interval 0.28 to 0.71) but not girls (871 pairs, 0.10, −0.09 to 0.30). The effect in boys remained after differences in birth order, maternal smoking, and head circumference were adjusted for and in an analysis restricted to children with birth weight ≥ 2500 g. Conclusion: The increase in childhood IQ with birth weight continues well into the normal birth weight range. For boys this relation holds within same sex sibships and therefore cannot be explained by confounding from family social environment. What is already known on this topic IQ at school age is linked to birth weight among low birthweight babies Some evidence suggests the association might also apply to children of normal birth weight What this study adds IQ at age 7 years is linearly related to birth weight among children of normal birth weight The relation was not due to confounding by maternal or socioeconomic factors IQ is also associated with differences in birth weight between boy sibling pairs but not girls

Association of Postprandial Triglyceride and Retinyl Palmitate Responses With Newly Diagnosed Exercise-Induced Myocardial Ischemia in Middle-Aged Men and Women

Although strong evidence exists linking fasting plasma levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) to risk for development of coronary artery disease (CAD), the data in support of an independent role for fasting triglyceride (TG) concentrations are weak. Humans are in the postprandial state most of the day, however, and results from both basic and clinical studies suggest that postprandial TG levels may be atherogenic. Previous studies have not, however, attempted to determine if postprandial TG levels are associated with CAD independent of other traditional risk factors or plasma lipid levels, particularly fasting plasma concentrations of TG and HDL-C. Ninety-two men and 113 women (mean age, 51.6 and 53.6 years, respectively) were recruited from populations undergoing diagnostic exercise electrocardiographic or thallium stress tests at our medical centers. Twenty-six men and 24 women had positive tests. We chose exercise-induced myocardial ischemia (EIM) as the criterion for defining case and control subjects because we wanted participants who did not have a prior diagnosis of CAD. Blood samples were obtained for measurement of plasma TG, TG-rich lipoprotein TG, and retinyl palmitate (RP) levels 2, 3.5, 5, and 8 hours after the subjects had consumed a fatty test meal. Logistic regression models were developed to test for associations between each variable and case-control status. Among men but not women postprandial TG and RP responses were associated with EIMI independent of age, race, and smoking status. In the male group, the odds ratio (OR) for an increase in postprandial TG response of approximately 1 SD was 1.69 (P = .007); the OR for an increase in RP response of 1 SD was 2.47 (P = .011). However, when fasting TG was added to the model, the OR for postprandial TG area in the men was reduced to 1.44 (P = .17); the OR postprandial RP area in the men was reduced to 1.88 (P = .12). There was no effect of adding other risk factors, including LDL-C and HDL-C, to the model. Significant effect modification by body mass index (BMI) on the relationship between postprandial responses and case-control status was observed. In men with BMI < 30, the OR was 1.83 for postprandial TG (P = .041) and 2.77 for postprandial RP (P = .032) in models that included fasting TG, LDL-C, and hypertension.

Enhanced reverse transcriptase-polymerase chain reaction for prostate specific antigen as an indicator of true pathologic stage in patients with prostate cancer

Background. As up to 50% of all patients with prostate cancer who have undergone radical prostatectomy are found to be understaged subsequent to surgery, a more sensitive early staging modality currently is needed. A molecular assay that detects prostate specific antigen (PSA)‐synthesizing cells in the peripheral circulation of patients with prostate cancer is described.

Risk factors for late onset gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit.

Background: Gram-negative bloodstream infections (BSIs) cause 20–30% of late onset sepsis in neonatal intensive care unit (NICU) patients and have mortality rates of 30–50%. We investigated risk factors for late onset Gram-negative sepsis in very low birth weight (<1500 g) NICU patients. Methods: We performed a case-control study as part of a larger 2-year clinical trial that examined the effects of hand hygiene practices on hospital-acquired infections. In this substudy, a case was a very low birth weight infant with a hospital-acquired Gram-negative BSI; control subjects, matched on study site and hand hygiene product, were chosen randomly from the patients who did not have Gram-negative BSIs. Potential risk factors were analyzed by Mantel-Haenszel methods and conditional logistic regression. Results: There were 48 cases of Gram-negative BSI. In multivariate analysis, we found that the following variables were significantly associated with Gram-negative BSI: central venous catheterization duration of >10 days; nasal cannula continuous positive airway pressure use; H2 blocker/proton pump inhibitor use; and gastrointestinal tract pathology. Conclusions: These analyses provide insights into potential strategies to reduce Gram-negative BSIs. Catheters should be removed as possible and H2 blockers/proton pump inhibitors should be used judiciously in NICU patients. The association between nasal cannula continuous positive airway pressure and Gram-negative BSIs requires further investigation. The association of gastrointestinal tract pathology with Gram-negative BSIs identifies a high risk group of neonates who may benefit from enhanced preventative strategies.

Oral manifestations of HIV infection in homosexual men and intravenous drug users: Study design and relationship of epidemiologic clinical, and immunologic parameters to oral lesions☆

This article describes the baseline findings from a study designed to compare the oral manifestations of HIV infection in homosexual men and intravenous drug users. Both seropositive and seronegative persons were studied. A standard examination instrument was developed to record indexes of oral disease as well as to record the presence of oral lesions. The two groups differed in terms of education, race, socioeconomic status, employment status, housing, and smoking experience. The prevalence and type of oral lesions differed in the two seropositive groups. In seropositive homosexual men, white lesions on the tongue (28.4%) predominated; whereas for the seropositive intravenous drug users, oral candidiasis (43.0%) and gingival marginal erythema (33.3%) were most often detected. We also observed that seronegative intravenous drug users displayed a greater number of oral lesions than seronegative homosexual men. For seropositive homosexual men, lesion presence was significantly associated with decreased levels of CD4; positive associations were seen with current smoking, antiviral drug use, and antibiotic use, and a negative association was observed with current employment. In contrast, only exposure to antiviral drugs was significantly correlated with lesion presence for seropositive intravenous drug users. This baseline analysis from our longitudinal study suggests clear differences in oral manifestations of HIV infection between seropositive homosexual men and intravenous drug users and between seronegative homosexual men and intravenous drug users. Among other parameters, it is apparent that lifestyle, access to health care, and the condition of the oral cavity before infection influence the development of oral lesions in persons with HIV infection.

Oral lesions as markers of severe immunosuppression in HIV-infected homosexual men and injection drug users.

OBJECTIVES We examined the diagnostic utility of the presence of oral lesions, individually and in combination, in identifying severe immunosuppression, defined as CD4 cell count under 200. STUDY DESIGN Data were collected on 82 HIV-seropositive homosexual men and 82 HIV-seropositive injection drug users who volunteered to participate in a longitudinal study of HIV infection. CD4 cell counts were measured within 24 hours of oral examination. METHODS Sensitivity, specificity, positive predictive value, negative predictive value, and the odds ratio were computed to assess the association between oral lesions and CD4 less than 200. In addition to the individual lesions, we studied the diagnostic properties of sets of three to six lesions. For each set of lesions, a patient was classified as positive for the set if he or she had one or more lesions in that set. RESULTS In homosexual men and injection drug users, individual lesions had low sensitivity, high specificity, and moderate positive and negative predictive values. Odds ratios reflected weak correlation to immunosuppression. When lesion sets were considered in homosexual men, sensitivity rose dramatically with only modest decreases in specificity. The positive and negative predictive values remained almost the same. Similar results for lesion sets were obtained in injection drug users, with greater reduction in specificity but stable positive and negative predictive values. Odds ratios indicated that for homosexual men, the more lesions included in the set, the stronger the correlation with immunosuppression. For injection drug users, strong correlations were observed for all lesion sets. CONCLUSIONS Analysis of sensitivities and odds ratios in homosexual men suggest that it may be valid to note the occurrence of a greater number of oral lesions than is currently done in staging patients with HIV infection. Among injection drug users, monitoring a larger number of lesions neither improves nor reduces the correlation to severe immunosuppression.

Strengthening the Career Development of Clinical Translational Scientist Trainees: A Consensus Statement of the Clinical Translational Science Award (CTSA) Research Education and Career Development Committees

The challenges for scholars committed to successful careers in clinical and translational science are increasingly well recognized. The Education and Career Development (EdCD) of the national Clinical and Translational Science Award consortium gathered thought leaders to propose sustainable solutions and an agenda for future studies that would strengthen the infrastructure across the spectrum of pre‐ and postdoctoral, MD and PhD, scholars. Six consensus statements were prepared that include: (1) the requirement for career development of a qualitatively different investigator; (2) the implications of interdisciplinary science for career advancement including institutional promotion and tenure actions that were developed for discipline‐specific accomplishments; (3) the need for long‐term commitment of institutions to scholars; (4) discipline‐specific curricula are still required but curricula designed to promote team work and interdisciplinary training will promote innovation; (5) PhD trainees have many pathways to career satisfaction and success; and (6) a centralized infrastructure to enhance and reward mentoring is required. Several themes cut across all of the recommendations including team science, innovation, and sustained institutional commitment. Implied themes include an effective and diverse job force and the requirement for a well‐crafted public policy that supports continued investments in science education. Clin Trans Sci 2012; Volume #: 1–6

Identifying and aligning expectations in a mentoring relationship.

The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar’s research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities. Clin Trans Sci 2011; Volume 4: 439–447

A comparison of regression approaches for analyzing clustered data.

OBJECTIVES We used 3 approaches to analyzing clustered data to assess the impact of model choice on interpretation. METHODS Approaches 1 and 2 specified random intercept models but differed in standard versus novel specification of covariates, which impacts ability to separate within- and between-cluster effects. Approach 3 was based on standard analysis of paired differences. We applied these methods to data from the National Collaborative Perinatal Project to examine the association between head circumference at birth and intelligence (IQ) at age 7 years. RESULTS Approach 1, which ignored within- and between-family effects, yielded an overall IQ effect of 1.1 points (95% confidence interval [CI]=0.9, 1.3) for every 1-cm increase in head circumference. Approaches 2 and 3 found comparable within-family effects of 0.6 points (95% CI = 0.4, 0.9) and 0.69 points (95% CI = 0.4, 1.0), respectively. CONCLUSIONS Our findings confirm the importance of applying appropriate analytic methods to clustered data, as well as the need for careful covariate specification in regression modeling. Method choice should be informed by the level of interest in cluster-level effects and item-level effects.

Building Interdisciplinary Research Models: A Didactic Course to Prepare Interdisciplinary Scholars and Faculty

Many academicians assume that anyone can engage in interdisciplinary research, but it is clear that successful interdisciplinary efforts require mastery of specific competencies that can be learned and improved. This paper describes the development and implementation of a course designed for Master’s, pre‐ and postdoctoral students and research faculty on models of interdisciplinary research skills, based on a set of core competencies. Major challenges included working through institutional structures that made it difficult to offer cross‐school courses, and interpersonal challenges among a diverse group of students from a number of disciplines. Although universities may be poised for interdisciplinary research, strategies for faculty preparation and support are lacking. Institutions embracing the concept of team and interdisciplinary science must focus not only on the structural barriers and facilitators, but also on direct support to faculty. The didactic course described in this paper is one approach to enhance interdisciplinary research skills of scholars‐in‐training and faculty, and we recommend that similar efforts be widely implemented. Clin Trans Sci 2011; Volume 4: 38–41