Aims/hypothesis
Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, ...we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
Methods
A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.
Results
A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.
Conclusions/interpretation
Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.
Aims/hypothesis
Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of ...sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults.
Methods
We established a case–cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case–cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence.
Results
In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence.
Conclusions/interpretation
This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.
The integrator SSS performs accurate
N
-body simulations of the Solar System when there is a mix of massive bodies and test particles. The orbital motion of all bodies at all times is integrated ...using a 12-10 explicit Runge-Kutta Nyström (RKN) pair. The test particles are divided into sets and each set integrated on a different processor. The explicit RKN pair uses an order 12 interpolant for the position and velocity when checking for collisions. We report on two significant improvements to SSS. The first improvement reduced the local round-off error in interpolated values by approximately four orders of magnitude, permitting more accurate modelling of collisions. The technique used to reduce the round-off error can be applied to other high-order interpolants. The second improvement is hand optimization of the implementation of SSS. This optimization increased the speed of SSS by approximately 60%, permitting more accurate modelling through the use of more test particles. We also present a summary of the numerical performance of SSS on a simulation of the Sun, the planets Earth to Neptune, and 500,000 test particles over 100 million years.
Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI ...with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16,154 participants and 12,403 incident cases of T2D were identified from 340,234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.
Summary
Carbamylation is a post‐translational modification that can be detected on a range of proteins, including immunoglobulin (Ig)G, in several clinical conditions. Carbamylated IgG (ca‐IgG) was ...reported to lose its capacity to trigger complement activation, but the mechanism remains unclear. Because C1q binds with high affinity to hexameric IgG, we analyzed whether carbamylation of IgG affects binding of C1q, hexamerization and complement‐dependent cytotoxicity (CDC). Synovial tissues of rheumatoid arthritis (RA) patients were analyzed for the presence of ca‐IgG in vivo. Synovial tissues from RA patients were analyzed for the presence of ca‐IgG using mass spectrometry (MS). Monomeric or hexameric antibodies were carbamylated in vitro and quality in solution was controlled. The capacity of ca‐IgG to activate complement was analyzed in enzyme‐linked immunosorbent (ELISAs) and cellular CDC assays. Using MS, we identified ca‐IgG to be present in the joints of RA patients. Using in vitro carbamylated antibodies, we observed that ca‐IgG lost its capacity to activate complement in both solid‐phase and CDC assays. Mixing ca‐IgG with non‐modified IgG did not result in effective inhibition of complement activation by ca‐IgG. Carbamylation of both monomeric IgG and preformed hexameric IgG greatly impaired the capacity to trigger complement activation. Furthermore, upon carbamylation, the preformed hexameric IgG dissociated into monomeric IgG in solution, indicating that carbamylation influences both hexamerization and C1q binding. In conclusion, ca‐IgG can be detected in vivo and has a strongly reduced capacity to activate complement which is, in part, mediated through a reduced ability to form hexamers.
Carbamylation of both monomeric IgG and pre‐formed hexameric IgG greatly impaired the capacity to trigger complement activation. Upon carbamylation the pre‐formed hexameric IgG, dissociated into monomeric IgG in solution. Indicating that carbamylation does not only influence C1q binding, but also the ability to form hexamers.
Inferred amino acid sequences of the methyl coenzyme-M reductase (mcrA) gene from five different methanogen species were aligned and two regions with a high degree of homology flanking a more ...variable region were identified. Analysis of the DNA sequences from the conserved regions yielded two degenerate sequences from which a forward primer, a 32-mer, and a reverse primer, a 23-mer, could be derived for use in the specific PCR-based detection of methanogens. The primers were successfully evaluated against 23 species of methanogen representing all five recognized orders of this group of Archaea, generating a PCR product between 464 and 491 bp. Comparisons between the mcrA and 16S small subunit rRNA gene sequences using PHYLIP demonstrated that the tree topologies were strikingly similar. Methods were developed to enable the analysis of methanogen populations in landfill using the mcrA gene as the target. Two landfill sites were examined and 63 clones from a site in Mucking, Essex, and 102 from a site in Odcombe, Somerset, were analysed. Analysis revealed a far greater diversity in the methanogen population within landfill material than has been seen previously.
Objective
As inspired oxygen availability falls with ascent to altitude, some individuals develop high‐altitude headache (HAH). We postulated that HAH results when hypoxia‐associated increases in ...cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies.
Methods
In high‐altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea‐level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores 0–4 ≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea‐level hypoxic study, 11 subjects underwent gadolinium‐enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen = 0.11, 1 hour).
Results
In the high‐altitude studies, headache burden correlated with both RVD (Spearman rho = 0.55, p = 0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r = −0.56, p = 0.03). It also related inversely to both the lateral + third ventricle summed volumes (Spearman rho = −0.5, p = 0.05) and pericerebellar CSF volume (r = −0.56, p = 0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r = ‐0.66, p < 0.05 and r = −0.75, p < 0.05, respectively).
Interpretation
Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia‐related increases in cerebral arterial flow occur. ANN NEUROL 2013;73:381–389
EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of ...intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (<weblink xlink:type="simple" xlink:href="http://empire10.isi.uu.nl" xmlns:xlink="http://www.w3.org/1999/xlink">http://empire10.isi.uu.nl ). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.
ABSTRACT We present and analyze the performance of a new algorithm for performing accurate simulations of the solar system when collisions between massive bodies and test particles are permitted. The ...orbital motion of all bodies at all times is integrated using a high-order variable-timestep explicit Runge-Kutta Nyström (ERKN) method. The variation in the timestep ensures that the orbital motion of test particles on eccentric orbits or close to the Sun is calculated accurately. The test particles are divided into groups and each group is integrated using a different sequence of timesteps, giving a multirate algorithm. The ERKN method uses a high-order continuous approximation to the position and velocity when checking for collisions across a step. We give a summary of the extensive testing of our algorithm. In our largest simulation-that of the Sun, the planets Earth to Neptune and 100,000 test particles over 100 million years-the relative error in the energy after 100 million years was of the order of 10−11.
Increased thyrotrophin‐stimulating hormone β (TSHβ) expression in the pars tuberalis is assumed to be an early step in the neuroendocrine mechanism transducing photoperiodic information. The present ...study aimed to determine the relationship between long‐photoperiod (LP) and diurnal TSHβ gene expression in the juvenile chicken by comparing LP‐photostimulated birds with groups kept on a short photoperiod (SP) for 1 or 12 days. TSHβ expression increased by 3‐ and 23‐fold after 1 and 12 days of LP‐photostimulation both during the day and at night. Under both SP and LP conditions, TSHβ expression was between 3‐ and 14‐fold higher at night than in the day, suggesting that TSHβ expression cycles in a diurnal pattern irrespective of photoperiod. The ratio of DIO2/3 was decreased on LPs, consequent to changes in DIO3 expression, although there was no evidence of any diurnal effect on DIO2 or DIO3 expression. Plasma prolactin concentrations revealed both an effect of LPs and time‐of‐day. Thus, TSHβ expression changes in a dynamic fashion both diurnally and in response to photoperiod.
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