Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease

Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10−19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients

Prevalence and course of mood and anxiety disorders, and correlates of symptom severity in adolescents with type 1 diabetes:Results from diabetes LEAP

Objectives We aim to determine the prevalence and the course of anxiety and mood disorders in Dutch adolescents (12-18 years old) with type 1 diabetes, and to examine correlates of symptom severity, including parental emotional distress. Methods Participants were 171 adolescents and 149 parents. The Diagnostic Interview Schedule for Children-IV was used to assess current, past year and lifetime anxiety and mood disorders in adolescents. Symptom severity and diabetes distress were measured with validated questionnaires. Correlates of these symptoms were examined using hierarchical regression analyses and included demographics (adolescent sex and age), clinical factors (diabetes duration, treatment modality, most recent glycated hemoglobin A1c ; all extracted from medical charts), adolescent diabetes distress, and parent emotional distress. Results Twenty-four (14%) adolescents met the criteria for ≥1 disorder(s) in the previous 12 months. Anxiety disorders were more prevalent than mood disorders (13% vs. 4%). Lifetime prevalence of anxiety and mood disorders was 29% (n = 49). The presence of any of these disorders earlier in life (from 5 years old up to 12 months prior to assessment) was associated with disorders in the past 12 months (OR = 4.88, p = 0.001). Higher adolescent diabetes distress was related to higher symptoms of anxiety (b = 0.07, p = 0.001) and depression (b = 0.13, p = 0.001), while demographics, clinical characteristics, and parental emotional distress were not related. Conclusions Anxiety and mood disorders are common among adolescents and related to earlier disorders. Higher diabetes distress was related to higher symptom severity. Clinicians are advised to address past psychological problems and remain vigilant of these problems

Discrete approaches to quantum gravity in four dimensions

The construction of a consistent theory of quantum gravity is a problem in theoretical physics that has so far defied all attempts at resolution. One ansatz to try to obtain a non-trivial quantum theory proceeds via a discretization of space-time and the Einstein action. I review here three major areas of research: gauge-theoretic approaches, both in a path-integral and a Hamiltonian formulation, quantum Regge calculus, and the method of dynamical triangulations, confining attention to work that is strictly four-dimensional, strictly discrete, and strictly quantum in nature.Comment: 33 pages, invited contribution to Living Reviews in Relativity; the author welcomes any comments and suggestion

Frame Dependence of Spin-One Angular Conditions in Light Front Dynamics

We elaborate the frame dependence of the angular conditions for spin-1 form factors. An extra angular condition is found in addition to the usual angular condition relating the four helicity amplitudes. Investigating the frame-dependence of the angular conditions, we find that the extra angular condition is in general as complicated as the usual one, although it becomes very simple in the $q^+ = 0$ frame involving only two helicity amplitudes. It is confirmed that the angular conditions are identical in frames that are connected by kinematical transformations. The high $Q^2$ behaviors of the physical form factors and the limiting behaviors in special reference frames are also discussed.Comment: 29 pages RevTeX. submitted to Phys. Rev.

High-resolution spectroscopy of the R Coronae Borealis and Other Hydrogen Deficient Stars

High-resolution spectroscopy is a very important tool for studying stellar physics, perhaps, particularly so for such enigmatic objects like the R Coronae Borealis and related Hydrogen deficient stars that produce carbon dust in addition to their peculiar abundances. Examples of how high-resolution spectroscopy is used in the study of these stars to address the two major puzzles are presented: (i) How are such rare H-deficient stars created? and (ii) How and where are the obscuring soot clouds produced around the R Coronae Borealis stars?Comment: 16 pages, 9 figures, Astrophysics and Space Science Proceedings, Springer-Verlag, Berlin, 201

Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients:Results of the TransplantLines Biobank and Cohort Study

Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (pinteraction < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 ± 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0-55.3) µmol/L. Through a median follow-up of 9.5 (IQR, 6.3‒10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1-SD increment, 0.69; 95% CI 0.54-0.89; p = 0.004), particularly among KTR with triglycerides ≥1.9 mmol/L (HR 0.46; 95% CI 0.30-0.70; p < 0.001; pinteraction = 0.01) and among KTR with HDL cholesterol ≥0.91 mmol/L (HR 0.56; 95% CI 0.38-0.84; p = 0.01; pinteraction = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C‒targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies

How grazing management can maximize erosion resistance of salt marshes

Combining natural saltmarsh habitats with conventional barriers can provide a sustainable and cost-effective alternative for fully engineered flood protection, provided that a minimal salt marsh width can be guaranteed for a long period. Hence, it is essential to understand both the key factors and management options driving the lateral erodibility/stability of salt marshes.We aimed to determine how salt marsh management (i.e. grazing by large vs. small grazers vs. artificial mowing), marsh elevation and marsh age affect soil stability (i.e. soil collapse) and intrinsic lateral erodibility of salt marshes (i.e. particle-by-particle detachment). Soil cores were collected in high and low marshes (above and below 0.5 m MHWL, respectively) of different ages. At these locations, we compared cores from grazed areas to cores inside grazer exclosures, with and without artificial mowing. All cores were exposed to waves in flumes to test their stability and lateral erodibility.All soil cores were characterized by a stable fine-grained layer deposited on top of readily erodible sand. The thickness of the fine-grained layer was a key parameter in reducing salt marsh instability (cliff collapse). This layer thickness increased with marsh age and at lower elevations, but decreased with cattle grazing due to compaction.The erosion resistance of the fine-grained layer increased with (a) large grazers that compacted the soil by trampling, (b) mowing that excluded soil-bioturbating species, and (c) grazing by small grazers that promoted vegetation types with higher root density.Synthesis and applications. Overall, marshes with thinner cohesive and/or fine-grained top layers are more sensitive to lateral erosion than marshes with deep cohesive soils, independently of the management. Grazing and artificial mowing can reduce the erodibility of fine-grained soils, making salt marshes more resilient to lateral erosion. However, compaction by large grazers simultaneously leads to thinner fine-grained layers and lower elevation, potentially leading to more inundation under sea-level rise. Hence, to effectively manage salt marshes to enhance their contribution to coastal protection, we recommend (a) moderate/rotational livestock grazing, avoiding high intensity grazing in sediment-poor systems sensitive to sea-level rise and (b) investigating measures to preserve small grazers.</p

Mesoscopic proximity effect in double barrier Superconductor/Normal Metal junctions

We report transport measurements down to T=60mK of SININ and SNIN structures in the diffusive limit. We fabricated Al-AlOx/Cu/AlOx/Cu (SININ) and Al/Cu/AlOx/Cu (SNIN) vertical junctions. For the first time, a zero bias anomaly was observed in a metallic SININ structure. We attribute this peak of conductance to coherent multi-reflections of electrons between the two tunnel barriers. This conductance maximum is quantitatively fitted by the relevant theory of mesoscopic SININ structures. When the barrier at the SN interface is removed (SNIN structure), we observe a peak of conductance at finite voltage accompagnied by an excess of sub-gap conductance.Comment: 4 pages, 4 figures, editorially approved for publication in Phys. Rev. B Rapid Com

Designing Genome-Wide Association Studies: Sample Size, Power, Imputation, and the Choice of Genotyping Chip

Genome-wide association studies are revolutionizing the search for the genes underlying human complex diseases. The main decisions to be made at the design stage of these studies are the choice of the commercial genotyping chip to be used and the numbers of case and control samples to be genotyped. The most common method of comparing different chips is using a measure of coverage, but this fails to properly account for the effects of sample size, the genetic model of the disease, and linkage disequilibrium between SNPs. In this paper, we argue that the statistical power to detect a causative variant should be the major criterion in study design. Because of the complicated pattern of linkage disequilibrium (LD) in the human genome, power cannot be calculated analytically and must instead be assessed by simulation. We describe in detail a method of simulating case-control samples at a set of linked SNPs that replicates the patterns of LD in human populations, and we used it to assess power for a comprehensive set of available genotyping chips. Our results allow us to compare the performance of the chips to detect variants with different effect sizes and allele frequencies, look at how power changes with sample size in different populations or when using multi-marker tags and genotype imputation approaches, and how performance compares to a hypothetical chip that contains every SNP in HapMap. A main conclusion of this study is that marked differences in genome coverage may not translate into appreciable differences in power and that, when taking budgetary considerations into account, the most powerful design may not always correspond to the chip with the highest coverage. We also show that genotype imputation can be used to boost the power of many chips up to the level obtained from a hypothetical “complete” chip containing all the SNPs in HapMap. Our results have been encapsulated into an R software package that allows users to design future association studies and our methods provide a framework with which new chip sets can be evaluated