An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Escaping the Ashby limit for mechanical damping/stiffness trade-off using a constrained high internal friction interfacial layer.

The development of new materials with reduced noise and vibration levels is an active area of research due to concerns in various aspects of environmental noise pollution and its effects on health. Excessive vibrations also reduce the service live of the structures and limit the fields of their utilization. In oscillations, the viscoelastic moduli of a material are complex and it is their loss part - the product of the stiffness part and loss tangent - that is commonly viewed as a figure of merit in noise and vibration damping applications. The stiffness modulus and loss tangent are usually mutually exclusive properties so it is a technological challenge to develop materials that simultaneously combine high stiffness and high loss. Here we achieve this rare balance of properties by filling a solid polymer matrix with rigid inorganic spheres coated by a sub-micron layer of a viscoelastic material with a high level of internal friction. We demonstrate that this combination can be experimentally realised and that the analytically predicted behaviour is closely reproduced, thereby escaping the often termed 'Ashby' limit for mechanical stiffness/damping trade-off and offering a new route for manufacturing advanced composite structures with markedly reduced noise and vibration levels

Closing in on Asymmetric Dark Matter I: Model independent limits for interactions with quarks

It is argued that experimental constraints on theories of asymmetric dark matter (ADM) almost certainly require that the DM be part of a richer hidden sector of interacting states of comparable mass or lighter. A general requisite of models of ADM is that the vast majority of the symmetric component of the DM number density must be removed in order to explain the observed relationship $\Omega_B\sim\Omega_{DM}$ via the DM asymmetry. Demanding the efficient annihilation of the symmetric component leads to a tension with experimental limits if the annihilation is directly to Standard Model (SM) degrees of freedom. A comprehensive effective operator analysis of the model independent constraints on ADM from direct detection experiments and LHC monojet searches is presented. Notably, the limits obtained essentially exclude models of ADM with mass 1GeV$\lesssim m_{DM} \lesssim$ 100GeV annihilating to SM quarks via heavy mediator states. This motivates the study of portal interactions between the dark and SM sectors mediated by light states. Resonances and threshold effects involving the new light states are shown to be important for determining the exclusion limits.Comment: 18+6 pages, 18 figures. v2: version accepted for publicatio

Prevalence of cardiovascular risk factors in a middle-income country and estimated cost of a treatment strategy

BACKGROUND: We assessed the prevalence of risk factors for cardiovascular disease (CVD) in a middle-income country in rapid epidemiological transition and estimated direct costs for treating all individuals at increased cardiovascular risk, i.e. following the so-called "high risk strategy". METHODS: Survey of risk factors using an age- and sex-stratified random sample of the population of Seychelles aged 25–64 in 2004. Assessment of CVD risk and treatment modalities were in line with international guidelines. Costs are expressed as US$per capita per year. RESULTS: 1255 persons took part in the survey (participation rate of 80.2$45.6, i.e. $11.2 for high blood pressure,$3.8 for diabetes, and $30.6 for dyslipidemia (using generic drugs except for hypercholesterolemia). Cost for minimal follow-up medical care and laboratory tests amounted to$22.6. CONCLUSION: High prevalence of major risk factors was found in a rapidly developing country and costs for treatment needed to reduce risk factors in all high-risk individuals exceeded resources generally available in low or middle income countries. Our findings emphasize the need for affordable cost-effective treatment strategies and the critical importance of population strategies aimed at reducing risk factors in the entire population

On the Size and Flight Diversity of Giant Pterosaurs, the Use of Birds as Pterosaur Analogues and Comments on Pterosaur Flightlessness

The size and flight mechanics of giant pterosaurs have received considerable research interest for the last century but are confused by conflicting interpretations of pterosaur biology and flight capabilities. Avian biomechanical parameters have often been applied to pterosaurs in such research but, due to considerable differences in avian and pterosaur anatomy, have lead to systematic errors interpreting pterosaur flight mechanics. Such assumptions have lead to assertions that giant pterosaurs were extremely lightweight to facilitate flight or, if more realistic masses are assumed, were flightless. Reappraisal of the proportions, scaling and morphology of giant pterosaur fossils suggests that bird and pterosaur wing structure, gross anatomy and launch kinematics are too different to be considered mechanically interchangeable. Conclusions assuming such interchangeability—including those indicating that giant pterosaurs were flightless—are found to be based on inaccurate and poorly supported assumptions of structural scaling and launch kinematics. Pterosaur bone strength and flap-gliding performance demonstrate that giant pterosaur anatomy was capable of generating sufficient lift and thrust for powered flight as well as resisting flight loading stresses. The retention of flight characteristics across giant pterosaur skeletons and their considerable robustness compared to similarly-massed terrestrial animals suggest that giant pterosaurs were not flightless. Moreover, the term ‘giant pterosaur’ includes at least two radically different forms with very distinct palaeoecological signatures and, accordingly, all but the most basic sweeping conclusions about giant pterosaur flight should be treated with caution. Reappraisal of giant pterosaur material also reveals that the size of the largest pterosaurs, previously suggested to have wingspans up to 13 m and masses up to 544 kg, have been overestimated. Scaling of fragmentary giant pterosaur remains have been misled by distorted fossils or used inappropriate scaling techniques, indicating that 10–11 m wingspans and masses of 200–250 kg are the most reliable upper estimates of known pterosaur size

Socioeconomic inequalities in mortality, morbidity and diabetes management for adults with type 1 diabetes: A systematic review.

AIMS: To systematically review the evidence of socioeconomic inequalities for adults with type 1 diabetes in relation to mortality, morbidity and diabetes management. METHODS: We carried out a systematic search across six relevant databases and included all studies reporting associations between socioeconomic indicators and mortality, morbidity, or diabetes management for adults with type 1 diabetes. Data extraction and quality assessment was undertaken for all included studies. A narrative synthesis was conducted. RESULTS: A total of 33 studies were identified. Twelve cohort, 19 cross sectional and 2 case control studies met the inclusion criteria. Regardless of healthcare system, low socioeconomic status was associated with poorer outcomes. Following adjustments for other risk factors, socioeconomic status was a statistically significant independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies for adults with type 1 diabetes. There appeared to be an association between low socioeconomic status and some aspects of diabetes management. Although only 3 of 16 studies made adjustments for confounders and other risk factors, poor diabetes management was associated with lower socioeconomic status in 3/3 of these studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels of mortality and morbidity for adults with type 1 diabetes even amongst those with access to a universal healthcare system. The association between low socioeconomic status and diabetes management requires further research given the paucity of evidence and the potential for diabetes management to mitigate the adverse effects of low socioeconomic status

Metabonomic fingerprints of fasting plasma and spot urine reveal human pre-diabetic metabolic traits

Impaired glucose tolerance (IGT) which precedes overt type 2 diabetes (T2DM) for decades is associated with multiple metabolic alterations in insulin sensitive tissues. In an UPLC-qTOF-mass spectrometry-driven non-targeted metabonomics approach we investigated plasma as well as spot urine of 51 non-diabetic, overnight fasted individuals aiming to separate subjects with IGT from controls thereby identify pathways affected by the pre-diabetic metabolic state. We could clearly demonstrate that normal glucose tolerant (NGT) and IGT subjects clustered in two distinct groups independent of the investigated metabonome. These findings reflect considerable differences in individual metabolite fingerprints, both in plasma and urine. Pre-diabetes associated alterations in fatty acid-, tryptophan-, uric acid-, bile acid-, and lysophosphatidylcholine-metabolism, as well as the TCA cycle were identified. Of note, individuals with IGT also showed decreased levels of gut flora-associated metabolites namely hippuric acid, methylxanthine, methyluric acid, and 3-hydroxyhippuric acid. The findings of our non-targeted UPLC-qTOF-MS metabonomics analysis in plasma and spot urine of individuals with IGT vs NGT offers novel insights into the metabolic alterations occurring in the long, asymptomatic period preceding the manifestation of T2DM thereby giving prospects for new intervention targets

Heavy burden of non-communicable diseases at early age and gender disparities in an adult population of Burkina Faso: world health survey

<p>Abstract</p> <p>Background</p> <p>WHO estimates suggest that age-specific death rates from non-communicable diseases are higher in sub-Saharan Africa than in high-income countries. The objectives of this study were to examine, in Burkina Faso, the prevalence of non-communicable disease symptoms by age, gender, socioeconomic group and setting (rural/urban), and to assess gender and socioeconomic inequalities in the prevalence of these symptoms.</p> <p>Methods</p> <p>We obtained data from the Burkina Faso World Health Survey, which was conducted in an adult population (18 years and over) with a high response rate (4822/4880 selected individuals). The survey used a multi-stage stratified random cluster sampling strategy to identify participants. The survey collected information on socio-demographic and economic characteristics, as well as data on symptoms of a variety of health conditions. Our study focused on joint disease, back pain, angina pectoris, and asthma. We estimated prevalence correcting for the sampling design. We used multiple Poisson regression to estimate associations between non-communicable disease symptoms, gender, socioeconomic status and setting.</p> <p>Results</p> <p>The overall crude prevalence and 95% confidence intervals (CI) were: 16.2% [13.5; 19.2] for joint disease, 24% [21.5; 26.6] for back pain, 17.9% [15.8; 20.2] for angina pectoris, and 11.6% [9.5; 14.2] for asthma. Consistent relationships between age and the prevalence of non-communicable disease symptoms were observed in both men and women from rural and urban settings. There was markedly high prevalence in all conditions studied, starting with young adults. Women presented higher prevalence rates of symptoms than men for all conditions: prevalence ratios and 95% CIs were 1.20 [1.01; 1.43] for joint disease, 1.42 [1.21; 1.66] for back pain, 1.68 [1.39; 2.04] for angina pectoris, and 1.28 [0.99; 1.65] for asthma. Housewives and unemployed women had the highest prevalence rates of non-communicable disease symptoms.</p> <p>Conclusions</p> <p>Our work suggests that social inequality extends into the distribution of non-communicable diseases among social groups and supports the thesis of a differential vulnerability in Burkinabè women. It raises the possibility of an abnormally high rate of premature morbidity that could manifest as a form of premature aging in the adult population. Increased prevention, screening and treatment are needed in Burkina Faso to address high prevalence and gender inequalities in non-communicable diseases.</p

Are Reports of Psychological Stress Higher in Occupational Studies? A Systematic Review across Occupational and Population Based Studies

This study was funded by the UK Ministry of Defence (MoD)