Effect of Arterial Stiffness and Carotid Intima-Media Thickness Progression on the Risk of Dysglycemia, Insulin Resistance, and Dyslipidemia: a Temporal Causal Longitudinal Study

This is the final version. Available on open access from the American Heart Association via the DOI in this recordData Availability Statement: The informed consent obtained from ALSPAC participants does not allow the data to be made freely available through any third-party maintained public repository. However, data used for this submission can be made available on request to the ALSPAC Executive. The ALSPAC data management plan describes in detail the policy regarding data sharing, which is through a system of managed open access. Full instructions for applying for data access can be found here: http://www.bristol.ac.uk/alspac/researchers/access/. The ALSPAC study website contains details of all the data that are available (http://www.bristol.ac.uk/alspac/researchers/our-data/).BACKGROUND: We investigated the temporal causal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT) progression with the risk of dysglycemia, insulin resistance, and dyslipidemia. METHODS: We included 3862, 17.7-year-old, participants from the Avon Longitudinal Study of Parents and Children, followed up for 7 years. cfPWV, cIMT, and fasting plasma samples were repeatedly measured. We computed homeostatic model assessment (HOMA) of insulin resistance and percent pancreatic beta-cell function. Data were analyzed using logistic regression, linear mixed-effect, and cross-lagged structural equation models. RESULTS: A higher cfPWV at 17.7 years was associated with higher insulin at age 24.5 years (odds ratio, 1.25 [CI, 1.08-1.44]; P=0.003), which slightly attenuated after covariates adjustment. Higher cIMT at 17.7 years was associated with lower insulin (odds ratio, 0.06 [0.01-0.95]; P=0.046) at 24.5 years, after covariate adjustments. In mixed-effect models, the 7-year progression in cfPWV (predictor) was directly associated with the increase in triglyceride (outcome). cIMT progression was associated with the 7-year increase in LDL (low-density lipoprotein), triglyceride, and glucose. In cross-lagged models, higher cfPWV at 17.7 years was associated with higher insulin (β=0.06, SE, 0.12, P=0.014), HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years. However, insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 17.7 years were not associated with cfPWV at 24.5 years. Higher cIMT at 17.7 years was associated with reduced insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years, but not vice versa. Higher glucose at 17.7 years was associated with higher cfPWV and cIMT at 24.5 years only. CONCLUSIONS: Arterial stiffness in adolescence may be a causal risk factor for hyperinsulinemia and insulin resistance in young adulthood

Density of Common Complex Ocular Traits in the Aging Eye: Analysis of Secondary Traits in Genome-Wide Association Studies

Genetic association studies are identifying genetic risks for common complex ocular traits such as age-related macular degeneration (AMD). The subjects used for discovery of these loci have been largely from clinic-based, case-control studies. Typically, only the primary phenotype (e.g., AMD) being studied is systematically documented and other complex traits (e.g., affecting the eye) are largely ignored. The purpose of this study was to characterize these other or secondary complex ocular traits present in the cases and controls of clinic-based studies being used for genetic study of AMD. The records of 100 consecutive new patients (of any diagnosis) age 60 or older for which all traits affecting the eye had been recorded systematically were reviewed. The average patient had 3.5 distinct diagnoses. A subset of 10 complex traits was selected for further study because they were common and could be reliably diagnosed. The density of these 10 complex ocular traits increased by 0.017 log-traits/year (P = 0.03), ranging from a predicted 2.74 at age 60 to 4.45 at age 90. Trait-trait association was observed only between AMD and primary vitreomacular traction (P = 0.0009). Only 1% of subjects age 60 or older had no common complex traits affecting the eye. Extrapolations suggested that a study of 2000 similar subjects would have sufficient power to detect genetic association with an odds ratio of 2.0 or less for 4 of these 10 traits. In conclusion, the high prevalence of complex traits affecting the aging eye and the inherent biases in referral patterns leads to the potential for confounding by undocumented secondary traits within case-control studies. In addition to the primary trait, other common ocular phenotypes should be systematically documented in genetic association studies so that adjustments for potential trait-trait associations and other bias can be made and genetic risk variants identified in secondary analyses

Low-dimensional network formation in molten sodium carbonate

Molten carbonates are highly inviscid liquids characterized by low melting points and high solubility of rare earth elements and volatile molecules. An understanding of the structure and related properties of these intriguing liquids has been limited to date. We report the results of a study of molten sodium carbonate (Na2CO3) which combines high energy X-ray diffraction, containerless techniques and computer simulation to provide insight into the liquid structure. Total structure factors (Fx(Q)) are collected on the laser-heated carbonate spheres suspended in flowing gases of varying composition in an aerodynamic levitation furnace. The respective partial structure factor contributions to Fx(Q) are obtained by performing molecular dynamics simulations treating the carbonate anions as flexible entities. The carbonate liquid structure is found to be heavily temperature-dependent. At low temperatures a low-dimensional carbonate chain network forms, at T = 1100 K for example ~55% of the C atoms form part of a chain. The mean chain lengths decrease as temperature is increased and as the chains become shorter the rotation of the carbonate anions becomes more rapid enhancing the diffusion of Na+ ions

A pilot randomized controlled trial of a stepped care intervention package for depression in primary care in Nigeria

Background Depression is common in primary care and is often unrecognized and untreated. Studies are needed to demonstrate the feasibility of implementing evidence-based depression care provided by primary health care workers (PHCWs) in sub-Saharan Africa. We carried out a pilot two-parallel arm cluster randomized controlled trial of a package of care for depression in primary care. Methods Six primary health care centers (PHCC) in two Local Government Areas of Oyo State, South West Nigeria were randomized into 3 intervention and 3 control clinics. Three PHCWs were selected for training from each of the participating clinics. The PHCWs from the intervention clinics were trained to deliver a manualized multicomponent stepped care intervention package for depression consisting of psychoeducation, activity scheduling, problem solving treatment and medication for severe depression. Providers from the control clinics delivered care as usual, enhanced by a refresher training on depression diagnosis and management. Outcome measures Patient’s Health Questionnaire (PHQ-9), WHO quality of Life instrument (WHOQOL-Bref) and the WHO disability assessment schedule (WHODAS) were administered in the participants’ home at baseline, 3 and 6 months. Results About 98% of the consecutive attendees to the clinics agreed to have the screening interview. Of those screened, 284 (22.7%) were positive (PHQ-9 score ≥ 8) and 234 gave consent for inclusion in the study: 165 from intervention and 69 from control clinics. The rates of eligible and consenting participants were similar in the control and intervention arms. In all 85.9% (92.8% in intervention and 83% in control) of the participants were successfully administered outcome assessments at 6 months. The PHCWs had little difficulty in delivering the intervention package. At 6 months follow up, depression symptoms had improved in 73.0% from the intervention arm compared to 51.6% control. Compared to the mean scores at baseline, there was improvement in the mean scores on all outcome measures in both arms at six months. Conclusion The results provide support for the feasibility of conducting a fully-powered randomized study in this setting and suggest that the instruments used may have the potential to detect differences between the arms