Validity evidence for a novel multiple-choice question bank in the field of child abuse pediatrics.

BACKGROUND: Though child abuse pediatrics has been a board-certified subspecialty for 15 years, there are few formalized board preparation resources available. OBJECTIVE: The purpose of this project was to establish a multiple-choice question bank with sufficient validity evidence for use in preparation for the child abuse pediatrics board examination. PARTICIPANTS AND SETTING: The question bank was distributed via an electronic child abuse pediatrics mailing list. Participants completing the entire question bank included 27 board-certified child abuse pediatricians (CAPs), 19 board-eligible CAPs, and 18 CAP fellows. METHODS: We used Messick's framework to conduct the validity investigation, which includes five components: content evidence, response process, internal structure, relation to other variables, and consequences. Item analyses included difficulty index, discrimination index, and distractor analysis. We used Cronbach's alpha to estimate internal consistency reliability. We conducted linear regressions of scores on the question bank compared to in-training exam scores and career stage. RESULTS: Eighty-four participants completed part of the question bank, and 64 completed the entire question bank. Of the original 117 questions ("items"), 94 met inclusion criteria. The mean score among board-certified CAPs was 80 %, and among participants reporting passing third-year ITE scores was 81 %. Correlation coefficient of scores on this question bank by career stage was r = 0.94, and by year of fellowship was r = 0.99. Cronbach's alpha for internal consistency reliability was 0.83. CONCLUSIONS: This multiple-choice question bank is the first question bank with a robust validity investigation for use by child abuse pediatrics trainees.

WT1 expression is inversely correlated with MYCN amplification or expression and associated with poor survival in non-MYCN-amplified neuroblastoma.

Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. A striking feature of this tumor is its clinical heterogeneity. Several tumor progression markers have been delineated so far, among which MYCN amplification, which occurs in about 25% of total NB cases, with the percentage increasing to 30% in advanced stage NB. Although MYCN amplification is strongly correlated with NB of poor outcome, the MYCN status cannot alone predict all cases of poor survival in NB. Indeed NB without MYCN amplification (about 70-80% of NB) are not always favorable. WT1 was initially identified as a tumor suppressor gene involved in the development of a pediatric renal tumor (Wilms' tumor). Here, we describe an inverse correlation between WT1 expression and MYCN amplification and expression. However and most notably, our results show that WT1 gene expression is associated with a poor outcome for patients showing non-MYCN-amplified tumors. Thus WT1 expression is clinically significant in NB and may be a prognostic marker for better risk stratification and for an optimized therapeutic management of NB.

Analysis of the effect of occupational exposure to asbestos based on threshold regression modeling of case-control data.

We analyze the effect of occupational exposure to asbestos on the occurrence of lung cancer based on a recent French case-control (CC) study. We build a large collection of threshold regression models, data-adaptively select a better model by CC-weighted likelihood-based cross-validation and then fit this better model by CC-weighted maximum likelihood. The CC-weighting allows us to draw valid inferences from CC data without relying on a logistic regression. This is possible because the joint distribution of the indicator of being a case and matching variable is available beforehand owing to two studies independent from our data set. The implications of the fitted model in terms of years of life free of lung cancer lost due to the exposure to asbestos are discussed.

Testing independence between two sequential gap times in the presence of covariates.

In the risk analysis of sequential events, the successive gap times are often correlated, e.g. as a result of an individual heterogeneity. Correlation is usually accounted for by using a shared gamma-frailty model, where the variance φ of the random individual effect quantifies the correlation between gap times. This method is known to yield satisfactory estimates of covariate effects, but underestimates φ, which could result in a lack of power of the test of independence. We propose a new test of independence between two sequential gap times where the first is the time elapsed from the origin. The test is based on an approximation of the hazard of the second event given the first gap time in a frailty model, with a frailty distribution belonging to the power variance function family. Simulation results show an increased power of the new test compared with the test derived from the gamma-frailty model. In the realistic case where hazards are event specific, and using event-specific approaches, the proposed estimation of the variance of the frailty is less biased than the gamma-frailty based estimation for a wide range of values (φ < 2.5 with the set of parameters considered), and similar for higher values. As an illustration, the methods are applied to a previously analysed asthma prevention trial with results showing a significant positive association between the successive times to asthmatic events. We also analyse data from a cohort of HIV-seropositive patients in order to assess the effect of risk factors on the occurrence of two successive markers of progression of the HIV disease. The results demonstrate the ability of the proposed model to account for negative correlations between gap times.

Relationship between adipocyte size and adipokine expression and secretion.

CONTEXT: Adipocytes are known to release a variety of factors that may contribute to the proinflammatory state characteristic for obesity. This secretory function is considered to provide the basis for obesity-related complications such as type 2 diabetes and atherosclerosis. OBJECTIVE: To get a better insight into possible underlying mechanisms, we investigated the effect of adipocyte size on adipokine production and secretion. DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES: Protein secretion and mRNA expression in cultured adipocytes separated according to cell size from 30 individuals undergoing elective plastic surgery were investigated. RESULTS: The mean adipocyte volume of the four fractions ranged from 205 +/- 146 to 1.077 +/- 471 pl. There were strong linear correlations for the secretion of adipokines over time. Secretion of leptin, IL-6, IL-8, TNF-alpha, monocyte chemoattractant protein-1, interferon-gamma-inducible protein 10, macrophage inflammatory protein-1beta, granulocyte colony stimulating factor, IL-1ra, and adiponectin was positively correlated with cell size. After correction for cell surface, there was still a significant difference between fraction IV (very large) and fraction I (small cells), for leptin, IL-6, IL-8, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. In contrast, antiinflammatory factors such as IL-1ra and adiponectin lost their association after correction for cell surface area comparing fraction I and IV. In addition, there was a decrease of IL-10 secretion with increasing cell size. CONCLUSIONS: The results clearly suggest that adipocyte size is an important determinant of adipokine secretion. There seems to be a differential expression of pro- and antiinflammatory factors with increasing adipocyte size resulting in a shift toward dominance of proinflammatory adipokines largely as a result of a dysregulation of hypertrophic, very large cells.

Albumin inhibits adipogenesis and stimulates cytokine release from human adipocytes.

Bovine serum albumin (BSA) is commonly used in adipocyte experiments as a binding protein for fat-soluble substances. Therefore, it is of interest to investigate whether BSA per se is influencing the functioning of human adipocytes in vitro. In the present study, we investigated the potential of BSA to affect the proliferation and differentiation capacity of human preadipocytes. BSA was found to inhibit adipose differentiation in a dose-dependent manner (being significant at concentrations of 2.5 microM), whereas proliferation was not affected. We further investigated the effect of BSA on the secretory function of adipocytes focusing on the release of selected cytokines. Preadipocytes and freshly isolated adipocytes incubated with BSA secreted significantly higher amounts of IL-6, -8, and -10, and TNF-alpha compared with cells incubated without BSA. The effects on cytokine secretion seemed to reside at the level of gene expression because BSA increased TNF-alpha and IL-6 mRNA in a dose-dependent manner. The results of the present study indicate that the presence of BSA in the culture medium has considerable effects on adipocyte function in vitro. These effects should be carefully considered for in vitro studies of adipose tissue.