Structural equation model for estimating risk factors in type 2 diabetes mellitus in a Middle Eastern setting: evidence from the STEPS Qatar.

AIMS: Understanding type 2 diabetes mellitus is critical for designing effective diabetes prevention policies in Qatar and the Middle East. METHODS: Using the Qatar 2012 WHO STEPwise approach to surveillance survey, a subsample of 1224 Qatari participants aged 18-64 years was selected. Subjects had their fasting blood glucose levels tested, had not been diagnosed with or treated for diabetes, had a fasting time >12 hours and were not pregnant. We applied a hypothesized structural equation model (SEM) to assess sociodemographic, behavioral, anthropometric and metabolic variables affecting persons with type 2 diabetes mellitus. RESULTS: There is a direct effect of triglyceride levels (0.336) and body mass index (BMI) (0.164) on diabetes status. We also found that physical activity levels negatively affect BMI (-0.148) and positively affect high-density lipoprotein (HDL) (0.106); sociodemographic background negatively affects diet (-0.522) and BMI (-0.352); HDL positively affects total cholesterol (0.230) and has a negative effect on BMI (-0.108), triglycerides (-0.128) and waist circumference (-0.104). Diet has a positive effect on triglycerides (0.281) while family history of diabetes negatively affects total cholesterol (-0.104). BMI has a positive effect on waist circumference (0.788) and mediates the effects of physical activity over diabetes status (-0.028). BMI also mediates the effects that sociodemographic factors (-0.058) and physical activity (-0.024) have on diabetes status. BMI and HDL (-0.002) together mediate the effect of physical activity on diabetes status and similarly HDL and tryglycerides (-0.005) also mediate the effect of physical activity on diabetes status. Finally diet and tryglycerides mediate the effects that sociodemographic factors have on diabetes status (-0.049). CONCLUSIONS: This study's main finding is that triglyceride levels and BMI are the main variables directly affecting diabetes status in the Qatari population

Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells

Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133+ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro, confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double strand breaks (DSB) which co-localized with 'replication factories' and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (>1Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro. These data identify RS as a cancer stem cell-specific target with significant clinical potential

Comparative models of biological and social pathways to predict child growth through age 2 years from birth cohorts in Brazil, India, the Philippines, and South Africa

Background: Early growth faltering accounts for one-third of child deaths, and adversely impacts the health and human capital of surviving children. Social as well as biological factors contribute to growth faltering, but their relative strength and interrelations in different contexts have not been fully described. Objective: The aim of this study was to use structural equation modelling to explore social and biological multidetermination of child height at age 2 y in longitudinal data from 4 birth cohort studies in low- and middle-income countries. Methods: We analyzed data from 13,824 participants in birth cohort studies in Brazil, India, the Philippines, and South Africa. We used exploratory structural equation models, with height-for-age at 24 mo as the outcome to derive factors, and path analysis to estimate relations among a wide set of social and biological variables common to the 4 sites. Results: The prevalence of stunting at 24 mo ranged from 14.0% in Brazil to 67.7% in the Philippines. Maternal height and birthweight were strongly predictive of height-for-age at 24 mo in all 4 sites (all P values <0.001). Three social-environmental factors, which we characterized as “child circumstances,” “family socioeconomic status,” and “community facilities,” were identified in all sites. Each social-environmental factor was also strongly predictive of height-for-age at 24 mo (all P values <0.001), with some relations partly mediated through birthweight. The biological pathways accounted for 59% of the total explained variance and the social-environmental pathways accounted for 41%. The resulting path coefficients were broadly similar across the 4 sites. Conclusions: Early child growth faltering is determined by both biological and social factors. Maternal height, itself a marker of intergenerational deprivation, strongly influences child height at 2 y, including indirect effects through birthweight and social factors. However, concurrent social factors, many of which are modifiable, directly and indirectly contribute to child growth. This study highlights opportunities for interventions that address both biological and social determinants over the long and short term

Novice drivers’ individual trajectories of driver behavior over the first three years of driving

Identifying the changes in driving behavior that underlie the decrease in crash risk over the first few months of driving is key to efforts to reduce injury and fatality risk in novice drivers. This study represented a secondary data analysis of 1148 drivers who participated in the UK Cohort II study. The Driver Behavior Questionnaire was completed at 6 months and 1, 2 and 3 years after licensure. Linear latent growth models indicated significant increases across development in all four dimensions of aberrant driving behavior under scrutiny: aggressive violations, ordinary violations, errors and slips. Unconditional and conditional latent growth class analyses showed that the observed heterogeneity in individual trajectories was explained by the presence of multiple homogeneous groups of drivers, each exhibiting specific trajectories of aberrant driver behavior. Initial levels of aberrant driver behavior were important in identifying sub-groups of drivers. All classes showed positive slopes; there was no evidence of a group of drivers whose aberrant behavior decreased over time that might explain the decrease in crash involvement observed over this period. Male gender and younger age predicted membership of trajectories with higher levels of aberrant behavior. These findings highlight the importance of early intervention for improving road safety. We discuss the implications of our findings for understanding the behavioral underpinnings of the decrease in crash involvement observed in the early months of driving

Measuring errors and violations on the road: A bifactor modeling approach to the Driver Behavior Questionnaire

The Driver Behavior Questionnaire (DBQ) is a self-report measure of driving behavior that has been widely used over more than 20 years. Despite this wealth of evidence a number of questions remain, including understanding the correlation between its violations and errors sub-components, identifying how these components are related to crash involvement, and testing whether a DBQ based on a reduced number of items can be effective. We address these issues using a bifactor modeling approach to data drawn from the UK Cohort II longitudinal study of novice drivers. This dataset provides observations on 12,012 drivers with DBQ data collected at .5, 1, 2 and 3 years after passing their test. A bifactor model, including a general factor onto which all items loaded, and specific factors for ordinary violations, aggressive violations, slips and errors fitted the data better than correlated factors and second-order factor structures. A model based on only 12 items replicated this structure and produced factor scores that were highly correlated with the full model. The ordinary violations and general factor were significant independent predictors of crash involvement at 6 months after starting independent driving. The discussion considers the role of the general and specific factors in crash involvemen

Epidemiology and clinical presentation of dogs infected with sarcoptic mange

Sarcoptic mange in dog is a common parasitic dermatitis, especially in non-controlled, stray dogs that develop evocative clinical signs. The present study includes 48 dogs, with different backgrounds, both privately owned and dogs from shelters. We searched for predisposing factors for contacting sarcoptic mange, such as: age, sex, breed, source of contamination. Their age ranged from 1.15 months to 12 years (with more than a half being under 1 year old), they were mostly common or cross-breed dogs, and the sex ratio was almost equal, with 25 females and 23 males. All dogs were naturally infected with Sarcoptes scabiei, as confirmed by identification on the microscope of skin scrapings from different body areas. Furthermore, we aimed to have a general idea concerning the severity of infection with Sarcoptes scabiei in the dogs we studied. The dogs received a clinical score based on the evaluation of typical signs that appear in sarcoptic mange such as alopecia, erythema, scales/crusts and the extent of mange on the cutaneous surface on different body parts (head, trunk, legs, tail). The most affected body part was the head, followed by the trunk and the most scored sign was the extent of affected skin and alopecia. The treatment consisted in the administration of either afoxolaner (Nexgard®), twice at a monthly interval (2.7-6.9 mg/kg), either sarolaner (Simparica®), twice at a monthly interval (2-4 mg/kg), or doramectin (Dectomax®) 0.2 mg/kg, twice at 14 days interval

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure