Poor growth, social inequalities and coronary risk.

Data from 5 epidemiological studies, spanning an age range from childhood to late adult life, are used to investigate associations between components of height, used as markers of growth at different phases, and arterial stiffness, subclinical atherosclerosis and cardiovascular risk. The roles of prenatal growth and life course socioeconomic position are considered. In the 1946 Birth Cohort, shorter leg, but not trunk length, was associated with greater pulse pressure, a measure of arterial stiffness, in adult men and women. Longitudinal analyses suggested that these effects were due to a steeper rise of blood pressure with age, independent of potential confounders and mediators considered. In the Whitehall II Study, shorter leg and trunk length were both associated with adverse levels of several cardiovascular risk factors and also lower distensibility and greater stiffness of the carotid arteries in men. In a cross-sectional examination of Filipino-American women, coronary disease was most strongly associated with leg length, while diabetes prevalence was not associated with measures of growth, but highest in women who were socioeconomically disadvantaged in childhood and adulthood. Higher blood pressure levels were observed in children with shorter leg length, relative to total body height, of a contemporary US birth cohort at age 3 years. The contribution of prenatal growth was considered in all studies where birthweight was available and found to be limited. Finally, results from the first Whitehall Study suggested that associations between stature and cardiovascular mortality may differ by socioeconomic position. These findings lend some support to the hypothesis that factors limiting leg growth are associated with arterial stiffness, subclinical atherosclerosis and cardiovascular risk these associations may originate in childhood and be amplified with age. The specificity of leg length as a marker of early influences on growth that alter cardiovascular risk is questioned

Changing Winds: National Politics And Its Role In Funding For Rural Development In Alaska

Thesis (M.A.) University of Alaska Fairbanks, 2010The combination of the election of Senator Mark Begich in 2008, an increased emphasis on transparency, and a growing movement away from congressionally-directed spending (earmarks) and toward competitively-awarded and formula-based funding has the potential to drastically reduce federal funding for rural development in Alaska. Alaska's basic needs for infrastructure remain equivalent to those of some of the least developed nations of the world. Rural development projects in Alaska, however, fight an uphill battle for federal funding because rural populations are low in numbers and remote, costs of rural development in Alaska far exceed similar projects in the "lower 48," and changes in the U.S. Congress have drastically reduced Alaskans' ability to circumvent formula-based and competitively-awarded funding avenues. This thesis is an analysis of recent changes that affect rural development funding in Alaska, and it hypothesizes how rural development funding for Alaska may continue to change

Zur psychosozialen Situation ungeplant schwangerer Frauen

Diese Studie dokumentiert das Verhütungsverhalten ungeplant schwangerer Frauen und untersucht, welche Einflüsse mit unsicherem oder inkonsequentem Verhütungsverhalten in Zusammenhang stehen. Das Interesse galt außerdem Faktoren, die den Ausgang der Schwangerschaft beeinflussen. Fragebögen wurden an Beratungsstellen und gynäkologische Praxen verschickt; deren Mitarbeiter baten Frauen, die aktuell ungeplant schwanger waren, um ihre Teilnahme an der Studie. 37 Frauen schickten den anonymisierten Fragebogen zurück, diese entschieden sich zu ähnlichen Anteilen zur Abtreibung und Austragung der Schwangerschaft. Über zwei Drittel der Schwangeren hatten einen Verhütungsversuch unternommen, weniger als die Hälfte verhütete jedoch "konsequent" oder "sehr konsequent", und über 40% waren bei ihrer ungeplanten Schwangerschaft ein Risiko eingegangen

Experimental Evaluation of Ultrasonic Simulation Techniques in Anisotropic Material

The high performance of the available computer technology provides the possibility to simulate the real life for ultrasonic inspections in terms of primary ultrasonic data like rf-time signals. For isotropic material codes like Generalized Point Source Synthesis (GPSS) or Elastodynamic Finite Integration Technique (EFIT) and the theoretical predictions correlate well with experimental results. Recently, the codes mentioned above have been extended to operate also in anisotropic material. In a first step the codes GPSS and EFIT have been expanded to work in materials of parallel oriented columnar grain structure with transversely isotropic symmetry. In order to verify these codes a set of experiments was carried out on weld metal pads and on welds of defined grain structure. Radiation, propagation, reflexion on boundaries and interaction of the sound field with defects for the modes “through transmission” and “pulse echo” were simulated and compared with the experiment

Fractures around the shoulder in the skeletally immature:A scoping review

Fractures around the shoulder girdle in children are mainly caused by sports accidents. The clavicle and the proximal humerus are most commonly involved. Both the clavicle and the proximal humerus have a remarkable potential for remodeling, which is why most of these fractures in children can be treated conservatively. However, the key is to understand when a child benefits from surgical management. Clear indications for surgery of these fractures are lacking. This review focuses on the available evidence on the management of clavicle and proximal humerus fractures in children. The only strict indications for surgery for diaphyseal clavicle fractures in children are open fractures, tenting of the skin with necrosis, associated neurovascular injury, or a floating shoulder. There is no evidence to argue for surgery of displaced clavicle fractures to prevent malunion since most malunions are asymptomatic. In the rare case of a symptomatic malunion of the clavicle in children, corrective osteosynthesis is a viable treatment option. For proximal humerus fractures in children, treatment is dictated by the patient's age (and thus remodeling potential) and the amount of fracture displacement. Under ten years of age, even severely displaced fractures can be treated conservatively. From the age of 13 and onwards, surgery has better outcomes for severely displaced (Neer types III and IV) fractures. Between 10 and 13 years of age, the indications for surgical treatment are less clear, with varying cut-off values of angulation (30-60 degrees) or displacement (1/3 – 2/3 shaft width) in the current literature.</p

Multi-omic prediction of incident type 2 diabetes.

AIMS/HYPOTHESIS: The identification of people who are at high risk of developing type 2 diabetes is a key part of population-level prevention strategies. Previous studies have evaluated the predictive utility of omics measurements, such as metabolites, proteins or polygenic scores, but have considered these separately. The improvement that combined omics biomarkers can provide over and above current clinical standard models is unclear. The aim of this study was to test the predictive performance of genome, proteome, metabolome and clinical biomarkers when added to established clinical prediction models for type 2 diabetes. METHODS: We developed sparse interpretable prediction models in a prospective, nested type 2 diabetes case-cohort study (N=1105, incident type 2 diabetes cases=375) with 10,792 person-years of follow-up, selecting from 5759 features across the genome, proteome, metabolome and clinical biomarkers using least absolute shrinkage and selection operator (LASSO) regression. We compared the predictive performance of omics-derived predictors with a clinical model including the variables from the Cambridge Diabetes Risk Score and HbA1c. RESULTS: Among single omics prediction models that did not include clinical risk factors, the top ten proteins alone achieved the highest performance (concordance index [C index]=0.82 [95% CI 0.75, 0.88]), suggesting the proteome as the most informative single omic layer in the absence of clinical information. However, the largest improvement in prediction of type 2 diabetes incidence over and above the clinical model was achieved by the top ten features across several omic layers (C index=0.87 [95% CI 0.82, 0.92], Δ C index=0.05, p=0.045). This improvement by the top ten omic features was also evident in individuals with HbA1c <42 mmol/mol (6.0%), the threshold for prediabetes (C index=0.84 [95% CI 0.77, 0.90], Δ C index=0.07, p=0.03), the group in whom prediction would be most useful since they are not targeted for preventative interventions by current clinical guidelines. In this subgroup, the type 2 diabetes polygenic risk score was the major contributor to the improvement in prediction, and achieved a comparable improvement in performance when added onto the clinical model alone (C index=0.83 [95% CI 0.75, 0.90], Δ C index=0.06, p=0.002). However, compared with those with prediabetes, individuals at high polygenic risk in this group had only around half the absolute risk for type 2 diabetes over a 20 year period. CONCLUSIONS/INTERPRETATION: Omic approaches provided marginal improvements in prediction of incident type 2 diabetes. However, while a polygenic risk score does improve prediction in people with an HbA1c in the normoglycaemic range, the group in whom prediction would be most useful, even individuals with a high polygenic burden in that subgroup had a low absolute type 2 diabetes risk. This suggests a limited feasibility of implementing targeted population-based genetic screening for preventative interventions

Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank.

Background The causal relevance of elevated blood pressure for several cardiovascular diseases (CVDs) is uncertain, as is the population impact of blood pressure lowering. This study systematically assesses evidence of causality for various CVDs in a 2-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP). Methods and Results We investigated associations of genetically predicted SBP as predicted by 256 genetic variants with 21 CVDs in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376 703 participants of European ancestry, aged 40 to 69 years at recruitment. Genetically predicted SBP was positively associated with 14 of the outcomes (P<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease in a middle-aged to early late-aged UK-based population, population reductions in SBP were predicted to result in an overall 16.9% (95% CI, 12.2%-21.3%) decrease in morbidity for a 5-mm Hg decrease from a population mean of 137.7 mm Hg, 30.8% (95% CI, 22.8%-38.0%) decrease for a 10-mm Hg decrease, and 56.2% (95% CI, 43.7%-65.9%) decrease for a 22.7-mm Hg decrease in SBP (22.7 mm Hg represents a shift from the current mean SBP to 115 mm Hg). Conclusions Risk of many CVDs is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure

A Systematic Review of Biomarkers and Risk of Incident Type 2 Diabetes: An Overview of Epidemiological, Prediction and Aetiological Research Literature

$\textbf{BACKGROUND}$ Blood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D. We aimed to systematically review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field. $\textbf{METHODS AND FINDINGS}$ We systematically searched PubMed MEDLINE (January 2000 until March 2015) and Embase (until January 2016) databases for observational studies of biomarkers and incident T2D according to the 2009 PRISMA guidelines. We also searched availability of meta-analyses, Mendelian randomisation and prediction research for the identified biomarkers. We reviewed 3910 titles (705 abstracts) and 164 full papers and included 139 papers from 69 cohort studies that described the prospective relationships between 167 blood-based or urinary biomarkers and incident T2D. Only 35 biomarkers were reported in large scale studies with more than 1000 T2D cases, and thus the evidence for association was inconclusive for the majority of biomarkers. Fourteen biomarkers have been investigated using Mendelian randomisation approaches. Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association. In additional search for T2D prediction, we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers. Most biomarkers did not enhance the strength of prediction, but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia. $\textbf{CONCLUSIONS}$ This study presents an extensive review of the current state of the literature to inform the strategy for future interrogation of existing and newly described biomarkers for T2D. Many biomarkers have been reported to be associated with the risk of developing T2D. The evidence of their value in adding to understanding of causal pathways to disease is very limited so far. The utility of most biomarkers remains largely unknown in clinical prediction. Future research should focus on providing good genetic instruments across consortia for possible biomarkers in Mendelian randomisation, prioritising biomarkers for measurement in large-scale cohort studies and examining predictive utility of biomarkers for a given context.This study was supported by the Medical Research Council UK (grant reference no. MC_UU_12015/1), http://gtr.rcuk.ac.uk/projects?ref=MC_UU_12015/1; Netherlands Organization for Scientific Research (NWO project number 825.13.004), http://www.nwo.nl/en/research-and-results/research-projects/i/85/10585.html; Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013), http://www.emif.eu/about. GSK provided support in the form of salaries for DW, DJN, AS. Pfizer provided support in the form of salary to JMB

Chemical shifts and cluster structure

The 2p core-level electron binding energies of size-selected silicon cluster ions have been determined from soft x-ray photoionization efficiency curves. Local chemical shifts and global charging energy contributions to the 2p binding energy can be separated, because core-level and valence-band electron binding energies exhibit the same inverse radius dependence. The experimental 2p binding energy distributions show characteristic size-specific patterns that are well reproduced by the corresponding electronic density of states obtained from density functional theory modeling. These results demonstrate that 2p binding energies in silicon clusters are dominated by initial state effects, i.e., by the interaction with the local valence electron density, and can thus be used to corroborate structural assignments