748 research outputs found

    Mapping Snowmelt Progression in the Upper Indus Basin with Synthetic Aperture Radar

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    The Indus River is a vital resource for food security, ecosystem services, hydropower, and economy for millions of people living in Pakistan, India, China, and Afghanistan. Glacier and snowmelt from the high altitude Himalaya, Karakoram, and Hindu Kush mountain ranges are the largest drivers of discharge in the upper Indus Basin (UIB), and contribute significantly to Indus flows. Complex climatology and topography, coupled with the challenges of field study and meteorological measurement in these rugged ranges, elicit notable uncertainties in predicting seasonal runoff as well as cryospheric response to changes in climate. Here we utilize Sentinel-1 synthetic aperture radar (SAR) imagery to track ablation season development of wet snow in the Shigar Watershed of the Karakoram Mountains in Pakistan from 2015 to 2018. We exploit opportune local image acquisition times to highlight diurnal differences in radar indications of wet snow, and examine the spatial and temporal contexts of radar diurnal differences for 2015, 2017, and 2018 ablation seasons. Radar classifications for each ablation season show spatial and temporal patterns that indicate a dry winter snowpack undergoing diurnal surface melt-refreeze cycles, transitioning to surface snow that remains wet both day and night, and finally snow free conditions following melt out. Diurnally differing SAR signals may offer insights into important snowpack energy balance processes that precede melt out, which could provide useful constraints for both glacier mass balance modeling and runoff forecasting in remote alpine watersheds

    Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions

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    An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions Patients were randomly assigned to placebo (n=3401) or enalapril (n=3396) at doses of 2[middle dot]5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n=2569) and those without heart failure entered the prevention trial (n=4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, PEnalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29729/1/0000065.pd

    Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance.

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    The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.IMPORTANCE The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you.

    Lessons learned from COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life during Ramadan Fasting in Children and Adolescents living with Type 1 Diabetes

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    Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8-18 years (study=276, control=223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children’s care during lockdown (p=0.019). Patients had better compliance with treatment (p= 0.002), a reversed sleep pattern (p= 0.033), increased food intake (p=<0.001) and less exercise (p<0.001). Children and parents perceived better QoL during lockdown (p=<0.001) with no differences between their reports in “Diabetes Symptoms”, “Treatment Adherence” and “Communication” domains. Self and proxy reports were different in all domains during non-lockdown (p-values <0.001- 0.009). In gap analysis, although not statistically significant, the gap was approximated between children’s and parents’ perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics

    Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes

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    Objective: Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. Research Design and Methods: We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. Results: Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels (\geq75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 × 104^{−4}), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 × 103^{−3}) and CYP2R1 (P = 3.0 × 103^{−3}). Conclusions: Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes

    Marriage “sharia style”: everyday practices of Islamic morality in England

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    The growing visibility of Islam in the public spaces of Western societies is often interpreted in the media as a sign of Muslim radicalisation. This article questions this postulate by examining the flourishing Muslim marriage industry in the UK. It argues that these ‘halal’ services, increasingly popular among the young generation of British Muslims, reflect the semantic shifting of categories away from the repertoire of Islamic jurisprudence to cultural and identity labels visible in public space. Informed by long-term ethnographic fieldwork in the British field of Islamic law, this article examines a Muslim speed-dating event, which took place in central London in 2013. It investigates how Islamic morality is maintained and negotiated in everyday social interactions rather than cultivated via discipline and the pursuit of virtuous dispositions. Using Goffman’s “frame analysis” and his interpretation of the social as a space of “performances” as well as recent anthropological reflections on “ordinary ethics” (Lambek) and “everyday Islam” (Schielke, Osella and Soares), it examines the potential for such practices to define the contours of a new public culture where difference is celebrated as a form of distinction

    Serum Vitamin D and Risk of Prostate Cancer in a Case-Control Analysis Nested Within the European Prospective Investigation into Cancer and Nutrition (EPIC)

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    Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994–2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer
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