218 research outputs found

    New housing association development and its potential to reduce concentrations of deprivation: An English case study

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    Social housing across Western Europe has become significantly more residualised as governments concentrate on helping vulnerable households. Many countries are trying to reduce the concentrations of deprivation by building for a wider range of households and tenures. In England this policy has two main strands: (i) including other tenures when regenerating areas originally built as mono-tenure social housing estates and (ii) introducing social rented and low cost homeownership into new private market developments through planning obligations. By examining where new social housing and low cost home ownership homes have been built and who moves into them, this paper examines whether these policies achieve social mix and reduce spatial concentrations of deprivation. The evidence suggests that new housing association development has enabled some vulnerable households to live in areas which are not deprived, while some better off households have moved into more deprived areas. But these trends have not been sufficient to stem increases in deprivation in the most deprived areas

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Acclimatization of the crustose coralline alga Porolithon onkodes to variable pCO2

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    Ocean acidification (OA) has important implications for the persistence of coral reef ecosystems, due to potentially negative effects on biomineralization. Many coral reefs are dynamic with respect to carbonate chemistry, and experience fluctuations in pCO2 that exceed OA projections for the near future. To understand the influence of dynamic pCO2 on an important reef calcifier, we tested the response of the crustose coralline alga Porolithon onkodes to oscillating pCO2. Individuals were exposed to ambient (400 ??atm), high (660 ??atm), or variable pCO2 (oscillating between 400/660 ??atm) treatments for 14 days. To explore the potential for coralline acclimatization, we collected individuals from low and high pCO2 variability sites (upstream and downstream respectively) on a back reef characterized by unidirectional water flow in Moorea, French Polynesia. We quantified the effects of treatment on algal calcification by measuring the change in buoyant weight, and on algal metabolism by conducting sealed incubations to measure rates of photosynthesis and respiration. Net photosynthesis was higher in the ambient treatment than the variable treatment, regardless of habitat origin, and there was no effect on respiration or gross photosynthesis. Exposure to high pCO2 decreased P. onkodes calcification by >70%, regardless of the original habitat. In the variable treatment, corallines from the high variability habitat calcified 42% more than corallines from the low variability habitat. The significance of the original habitat for the coralline calcification response to variable, high pCO2 indicates that individuals existing in dynamic pCO2 habitats may be acclimatized to OA within the scope of in situ variability. These results highlight the importance of accounting for natural pCO2 variability in OA manipulations, and provide insight into the potential for plasticity in habitat and species-specific responses to changing ocean chemistry.Funding was provided by grants from the National Science Foundation (OCE-0417412, OCE-10-26852, OCE-1041270) and gifts from the Gordon and Betty Moore Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

    A novel μCT analysis reveals different responses of bioerosion and secondary accretion to environmental variability

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    Corals build reefs through accretion of calcium carbonate (CaCO3) skeletons, but net reef growth also depends on bioerosion by grazers and borers and on secondary calcification by crustose coralline algae and other calcifying invertebrates. However, traditional field methods for quantifying secondary accretion and bioerosion confound both processes, do not measure them on the same time-scale, or are restricted to 2D methods. In a prior study, we compared multiple environmental drivers of net erosion using pre- and post-deployment micro-computed tomography scans (μCT; calculated as the % change in volume of experimental CaCO3 blocks) and found a shift from net accretion to net erosion with increasing ocean acidity. Here, we present a novel μCT method and detail a procedure that aligns and digitally subtracts pre- and post-deployment μCT scans and measures the simultaneous response of secondary accretion and bioerosion on blocks exposed to the same environmental variation over the same time-scale. We tested our method on a dataset from a prior study and show that it can be used to uncover information previously unattainable using traditional methods. We demonstrated that secondary accretion and bioerosion are driven by different environmental parameters, bioerosion is more sensitive to ocean acidity than secondary accretion, and net erosion is driven more by changes in bioerosion than secondary accretion

    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Association analysis of ADPRT1, AKR1B1, RAGE, GFPT2 and PAI-1 gene polymorphisms with chronic renal insufficiency among Asian Indians with type-2 diabetes

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    <p>Abstract</p> <p>Background</p> <p>To determine association of nine single nucleotide polymorphisms (SNPs) in ADP ribosyltransferase-1 (ADPRT1), aldo-keto reductase family 1 member B1 (AKR1B1), receptor for advanced glycation end-products (RAGE), glutamine:fructose-6-phosphate amidotransferase-2 (GFPT2), and plasminogen activator inhibitor-1 (PAI-1) genes with chronic renal insufficiency (CRI) among Asian Indians with type 2 diabetes; and to identify epistatic interactionss between genes from the present study and those from renin-angiotensin-aldosterone system (RAAS), and chemokine-cytokine, dopaminergic and oxidative stress pathways (previously investigated using the same sample set).</p> <p>Methods</p> <p>Type 2 diabetes subjects with CRI (serum creatinine ≥3.0 mg/dl) constituted the cases (n = 196), and ethnicity and age matched individuals with diabetes for a duration of ≥ 10 years, normal renal functions and normoalbuminuria recruited as controls (n = 225). Allelic and genotypic constitution of 10 polymorphisms (SNPs) from five genes namely- <it>ADPRT1</it>, <it>AKR1B1, RAGE, GFPT2 </it>and <it>PAI-1 </it>with diabetic CRI was investigated. The genetic associations were evaluated by computation of odds ratio and 95% confidence interval. Multiple logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study epistatic interactions between SNPs in different genes.</p> <p>Results</p> <p>Single nucleotide polymorphisms -429 T>C in <it>RAGE </it>and rs7725 C>T SNP in 3' UTR in <it>GFPT2 </it>gene showed a trend towards association with diabetic CRI. Investigation using miRBase statistical tool revealed that rs7725 in <it>GFPT2 </it>was a perfect target for predicted miRNA (hsa miR-378) suggesting the presence of the variant 'T' allele may result in an upregulation of GFPT2 contributing to diabetic renal complication. Epistatic interaction between SNPs in transforming growth factor <it>TGF-β1 </it>(investigated using the same sample set and reported elsewhere) and <it>GFPT2 </it>genotype was observed.</p> <p>Conclusions</p> <p>Association of SNPs in <it>RAGE </it>and <it>GFPT2 </it>suggest that the genes involved in modulation of oxidative pathway could be major contributor to diabetic chronic renal insufficiency. In addition, GFPT2 mediated overproduction of TGF-β1 leading to endothelial expansion and thereby CRI seems likely, suggested by our observation of a significant interaction between GFPT2 with TGF-β1 genes. Further, identification of predicted miRNA targets spanning the associated SNP in <it>GFPT2 </it>implicates the rs7725 SNP in transcriptional regulation of the gene, and suggests <it>GFPT2 </it>could be a relevant target for pharmacological intervention. Larger replication studies are needed to confirm these observations.</p

    Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania

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    BACKGROUND: The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A(1c). RESULTS: Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure

    A Randomized Community-based Intervention Trial Comparing Faith Community Nurse Referrals to Telephone-Assisted Physician Appointments for Health Fair Participants with Elevated Blood Pressure

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    To measure the effect of faith community nurse referrals versus telephone-assisted physician appointments on blood pressure control among persons with elevated blood pressure at health fairs. Randomized community-based intervention trial conducted from October 2006 to October 2007 of 100 adults who had an average blood pressure reading equal to or above a systolic of 140 mm Hg or a diastolic of 90 mm Hg obtained at a faith community nurse-led church health event. Participants were randomized to either referral to a faith community nurse or to a telephone-assisted physician appointment. The average enrollment systolic blood pressure (SBP) was 149 ± 14 mm Hg, diastolic blood pressure (DBP) was 87 ± 11 mm Hg, 57% were uninsured and 25% were undiagnosed at the time of enrollment. The follow-up rate was 85% at 4 months. Patients in the faith community nurse referral arm had a 7 ± 15 mm Hg drop in SBP versus a 14 ± 15 mm Hg drop in the telephone-assisted physician appointment arm (p = 0.04). Twenty-seven percent of the patients in the faith community nurse referral arm had medication intensification compared to 32% in the telephone-assisted physician appointment arm (p = 0.98). Church health fairs conducted in low-income, multiethnic communities can identify many people with elevated blood pressure. Facilitating physician appointments for people with elevated blood pressure identified at health fairs confers a greater decrease in SBP than referral to a faith community nurse at four months

    High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

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    The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change

    Cellular binding partners of the human papillomavirus E6 protein

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    The high-risk strains of human papillomavirus (HR-HPV) are known to be causative agents of cervical cancer and have recently also been implicated in cancers of the oropharynx. E6 is a potent oncogene of HR-HPVs, and its role in the progression to malignancy has been and continues to be explored. E6 is known to interact with and subsequently inactivate numerous cellular proteins pivotal in the mediation of apoptosis, transcription of tumor suppressor genes, maintenance of epithelial organization, and control of cell proliferation. Binding of E6 to these proteins cumulatively contributes to the oncogenic potential of HPV. This paper provides an overview of these cellular protein partners of HR-E6, the motifs known to mediate oncoprotein binding, and the agents that have the potential to interfere with E6 expression and activity and thus prevent the subsequent progression to oncogenesis
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