Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

Facile, productive, and cost-effective synthesis of a novel tetrazine-based iron oxide nanoparticle for targeted image contrast agents and nanomedicines

We have developed an operationally simple, time, and cost-effective protocol to produce a novel tetrazine-based iron oxide nanoparticle using commercially available and inexpensive materials. Our protocol proceeds at room temperature and uses hexafluorophosphate azabenzotriazole tetramethyl uronium, a well-known, widely used reagent for the large-scale industrial production of important pharmaceuticals. The nanoparticles obtained have a diameter range between 16 and 21 nm and showed no toxicity against endothelial cell lines. The tetrazine moiety on the nanoparticle surface could potentially allow further attachment of specific targeting vectors by using so-called copper-free click chemistry. We therefore anticipate that our protocol can represent a significant breakthrough in the future development and commercialization of improved, tissue-specific contrast agents and drug delivery for clinical diagnosis, monitoring and therapy of diseases at an asymptomatic stage

An evaluation of iron bioavailability and speciation in western lake superior with the use of combined physical, chemical, and biological assessment

An iron-dependent cyanobacterial bioreporter (Synechococcus strain KAS101) was used in unison with sizefractionated iron content (.0.45, ,0.45, ,0.02 mm), and chemical characterization of iron complexation (C18 resin column) to elucidate the bioavailable forms of iron present in Lake Superior during periods of inverse thermal stratification (May) and strong thermal stratification (September) of the water column. The results provide evidence of organic complexation of iron in Lake Superior waters. Iron in most sampled water was complexed by organic compounds that behaved like fulvic acids, whereas some samples showed evidence for the presence of siderophore-like compounds. The presence of dissolved organic matter suppressed the cellular luminescence of the bioreporter, indicating an increased iron bioavailability. This effect could result either from the presence of siderophores forming iron complexes that are bioavailable to the bioreporter, or from more indirect effects because of the presence of other organic compounds, such as fulvic acids or polysaccharides. Model ligand additions, iron bioaccumulation, and photo-oxidation of dissolved organic matter were used to assess the bioavailability of organically complexed iron to the bioreporter. A significant fraction of the iron (40- 100%) was bioavailable to the bioreporter. Iron bioavailability was high enough for the bioreporter not to be iron limited in the water collected from Lake Superior. This measure of bioavailability to picocyanobacteria is relevant because picoplankton accounted for the majority of chlorophyll a in Lake Superior during this study. 2009, by the American Society of Limnology and Oceanography, Inc

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Effects of the Affordable Care Act Dependent Coverage Mandate on Health Insurance Coverage for Individuals in Same-Sex Couples

This is the final version. Available on open access from Duke University Press via the DOI in this recordA large body of research documents that the 2010 dependent coverage mandate of the U.S. Affordable Care Act was responsible for significantly increasing health insurance coverage among young adults. No prior research has examined whether sexual minority young adults also benefitted from the dependent coverage mandate despite previous studies showing lower health insurance coverage among sexual minorities. Our estimates from the American Community Survey, using difference-in-differences and event study models, show that men in same-sex couples aged 21-25 experienced a significantly greater increase in the likelihood of having any health insurance after 2010 than older, 27- to 31-year-old men in same-sex couples. This increase is concentrated among employer-sponsored insurance, and it is robust to permutations of periods and age groups. Effects for women in same-sex couples and men in different-sex couples are smaller than the associated effects for men in same-sex couples. These findings confirm the broad effects of expanded dependent coverage and suggest that eliminating the federal dependent mandate could reduce health insurance coverage among young adult sexual minorities in same-sex couples.Robert Wood Johnson Foundatio

Molecular networks of human muscle adaptation to exercise and age

Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity

Lunar resources: a review

There is growing interest in the possibility that the resource base of the Solar System might in future be used to supplement the economic resources of our own planet. As the Earth’s closest celestial neighbour, the Moon is sure to feature prominently in these developments. In this paper I review what is currently known about economically exploitable resources on the Moon, while also stressing the need for continued lunar exploration. I find that, although it is difficult to identify any single lunar resource that will be sufficiently valuable to drive a lunar resource extraction industry on its own (notwithstanding claims sometimes made for the 3He isotope, which are found to be exaggerated), the Moon nevertheless does possess abundant raw materials that are of potential economic interest. These are relevant to a hierarchy of future applications, beginning with the use of lunar materials to facilitate human activities on the Moon itself, and progressing to the use of lunar resources to underpin a future industrial capability within the Earth-Moon system. In this way, gradually increasing access to lunar resources may help ‘bootstrap’ a space-based economy from which the world economy, and possibly also the world’s environment, will ultimately benefit

Aberrant signaling in T-cell acute lymphoblastic leukemia: biological and therapeutic implications

T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL