A Bayesian nonparametric approach to dynamic item-response modeling: An application to the GUSTO cohort study.

Statistical analysis of questionnaire data is often performed employing techniques from item-response theory. In this framework, it is possible to differentiate respondent profiles and characterize the questions (items) included in the questionnaire via interpretable parameters. These models are often crosssectional and aim at evaluating the performance of the respondents. The motivating application of this work is the analysis of psychometric questionnaires taken by a group of mothers at different time points and by their children at one later time point. The data are available through the GUSTO cohort study. To this end, we propose a Bayesian semiparametric model and extend the current literature by: (i) introducing temporal dependence among questionnaires taken at different time points; (ii) jointly modeling the responses to questionnaires taken from different, but related, groups of subjects (in our case mothers and children), introducing a further dependency structure and therefore sharing of information; (iii) allowing clustering of subjects based on their latent response profile. The proposed model is able to identify three main groups of mother/child pairs characterized by their response profiles. Furthermore, we report an interesting maternal reporting bias effect strongly affecting the clustering structure of the mother/child dyads.

Determinants of intramyocellular lipid accumulation in early childhood.

BACKGROUND/OBJECTIVES: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. SUBJECTS/METHODS: This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. RESULTS: The mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. CONCLUSION: This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.

CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.

Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.

The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

Validation of prediction equations for resting energy expenditure in Singaporean Chinese men.

Accurate prediction of resting energy expenditure (REE) is important in establishing adequate dietary intake goals for effective weight management. Previous studies have shown that the validity of an energy prediction equation may depend on the ethnicity of the population. Validation studies are lacking in the Singaporean Chinese population. A total of 96 healthy Singaporean Chinese males of age 21­40 years and body mass index (BMI) 18.5­30.0 kg/m2 participated in this study. REE was measured by indirect calorimetry and compared with REE predicted using existing equations. Validity was evaluated on the basis of mean bias and percentage of subjects predicted within ±10% of REE measured. In addition, Bland and Altman analyses were performed. No significant difference was observed between the mean levels of measured and predicted REE derived from the Owen equation. The Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Harris­Benedict and Mifflin equations significantly overestimated the mean measured REE by 7.5%, 6.0% and 2.4% respectively. Percentage of valid predictions for FAO/WHO/UNU, Harris­Benedict, Mifflin and Owen equations were 60%, 67%, 75% and 73% respectively. Bland and Altman analyses demonstrated poor agreement for all equations. The Owen equation provided a valid estimation of REE in Singaporean Chinese men at a group level. However, the individual errors of the equations were unacceptable high and may have limited utility in making clinical decisions on nutritional requirements.

A multi-institutional survey on faculty development needs, priorities and preferences in medical education in an Asian medical school.

BACKGROUND: Faculty development in medical education is crucial for maintaining academic vitality. The authors conducted a needs assessment survey in Singapore to determine the educational needs and priorities of clinical faculty. METHODS: This study implemented a questionnaire-based, anonymous, multi-institutional survey with stratified random sampling. Each question was anchored with two statements on a 9-point scale. Respondents were asked to determine their current knowledge and the knowledge they would need in future. RESULTS: The response rate was 81.9%. Overall, the participants' current knowledge was rated either "modest" (scale 4-6) or "substantial" (scale 7-9), irrespective of teaching experience. Participants reported higher knowledge in areas related to teaching and modest knowledge in educational concepts and assessment. They reported a need for higher knowledge in most areas to function well as a teacher. CONCLUSION: The need for faculty development is universal and independent of teaching experience in this group. Teaching faculty from the institutes studied understood the need for improved knowledge in pedagogical knowledge.