1,751 research outputs found

    Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

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    A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the Mr 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p < 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ chain (p < 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies. We conclude that 64K antibodies, complement-fixing islet cell antibodies and insulin autoantibodies represent sensitive serological markers in assessing high risk for a progression to Type 1 diabetes in islet cell antibody positive non-diabetic individuals

    Microstructural evolution under low shear rates during Rheo processing of LM25 alloy

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    © ASM InternationalMicrostructural features of LM25 alloy processed by two different routes: (1) conventional casting, and(2)shear casting based on inclined heated surface are studied. The microstructures of the primary phase for the shear-cast samples show rosette or ellipsoidal morphologies. Heat transfer of contacting melt with the inclined tube surface and shear stress exerted on the layers of the melt as result of gravitational force are crucial parameters for the microstructural evolution. Compared to those produced by conventional casting, shear-cast samples have a much improved tensile strength and ductility due to globular microstructure

    Defining the key wintering habitats in the Sahel for declining African-Eurasian migrants using expert assessment

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    SummaryThe Sahel in West Africa is a major wintering area for many western Palearctic migrants. The breeding populations of many of these have declined over the past 50 years. However, there have been few intensive field studies on migrant ecology in the Sahel and these were generally within a very restricted area. Consequently our knowledge of the distribution of species within this extensive area and the habitat associations of these species is limited. Understanding these habitat associations is essential for the effective conservation management of populations. We brought together a group of experts and consulted a wider group by email to assess the main Sahelian habitat types used by 68 African-Eurasian migrant bird species. Those species that showed strongest declines during 1970–1990 were associated with more open habitats than those newly declining during 1990–2000, when declining species were associated with habitats with more shrubs and trees. Populations of species that winter in the Sahel are generally stable or increasing now as rainfall has increased and is now near the long-term average for the Sahel. Those which use the Sahel only as a staging area are, in many cases, in rapid decline at present.We would like to thank Andy Clements, Paul Donald, Lincoln Fishpool and Mike Mortimore for contributing to the workshop and Peter Jones, Ian Newton, Volker Salewski, Tim Wacher, Eddy Wymenga and Leo Zwarts for useful comments by email on draft habitat importance scores. This study was funded by the Newton Trust and the Cambridge Conservation Initiative Collaborative Fund, supported by Arcadia. WJS is funded by Arcadia.This is the accepted manuscript of a paper published in Bird Conservation International, Volume 24, Issue 04, December 2014, pp 477-491, DOI: http://dx.doi.org/10.1017/S0959270913000531, Published online: 24 February 201

    Traffic-related pollution and asthma prevalence in children. Quantification of associations with nitrogen dioxide.

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    Ambient nitrogen dioxide is a widely available measure of traffic-related air pollution and is inconsistently associated with the prevalence of asthma symptoms in children. The use of this relationship to evaluate the health impact of policies affecting traffic management and traffic emissions is limited by the lack of a concentration-response function based on systematic review and meta-analysis of relevant studies. Using systematic methods, we identified papers containing quantitative estimates for nitrogen dioxide and the 12 month period prevalence of asthma symptoms in children in which the exposure contrast was within-community and dominated by traffic pollution. One estimate was selected from each study according to an a priori algorithm. Odds ratios were standardised to 10 Όg/m(3) and summary estimates were obtained using random- and fixed-effects estimates. Eighteen studies were identified. Concentrations of nitrogen dioxide were estimated for the home address (12) and/or school (8) using a range of methods; land use regression (6), study monitors (6), dispersion modelling (4) and interpolation (2). Fourteen studies showed positive associations but only two associations were statistically significant at the 5 % level. There was moderate heterogeneity (I(2) = 32.8 %) and the random-effects estimate for the odds ratio was 1.06 (95 % CI 1.00 to 1.11). There was no evidence of small study bias. Individual studies tended to have only weak positive associations between nitrogen dioxide and asthma prevalence but the summary estimate bordered on statistical significance at the 5 % level. Although small, the potential impact on asthma prevalence could be considerable because of the high level of baseline prevalence in many cities. Whether the association is causal or indicates the effects of a correlated pollutant or other confounders, the estimate obtained by the meta-analysis would be appropriate for estimating impacts of traffic pollution on asthma prevalence

    Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

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    <p>Abstract</p> <p>Introduction</p> <p>The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone.</p> <p>Case presentation</p> <p>We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations.</p> <p>Conclusions</p> <p>The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic effect, appear primarily due to a reduced volume of distribution. The extent of plasma methadone binding may help to explain the unpredictability of its pharmacokinetics. Changes in volume of distribution due to plasma binding may represent important causes of clinically meaningful drug interactions.</p

    The differential hormonal milieu of morning versus evening, may have an impact on muscle hypertrophic potential

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    Substantial gains in muscle strength and hypertrophy are clearly associated with the routine performance of resistance training. What is less evident is the optimal timing of the resistance training stimulus to elicit these significant functional and structural skeletal muscle changes. Therefore, this investigation determined the impact of a single bout of resistance training performed either in the morning or evening upon acute anabolic signalling (insulin-like growth factor-binding protein-3 (IGFBP-3), myogenic index and differentiation) and catabolic processes (cortisol). Twenty-four male participants (age 21.4±1.9yrs, mass 83.7±13.7kg) with no sustained resistance training experience were allocated to a resistance exercise group (REP). Sixteen of the 24 participants were randomly selected to perform an additional non-exercising control group (CP) protocol. REP performed two bouts of resistance exercise (80% 1RM) in the morning (AM: 0800 hrs) and evening (PM: 1800 hrs), with the sessions separated by a minimum of 72 hours. Venous blood was collected immediately prior to, and 5 min after, each resistance exercise and control sessions. Serum cortisol and IGFBP-3 levels, myogenic index, myotube width, were determined at each sampling period. All data are reported as mean ± SEM, statistical significance was set at P≀0.05. As expected a significant reduction in evening cortisol concentration was observed at pre (AM: 98.4±10.5, PM: 49.8±4.4 ng/ml, P0.05). Timing of resistance training regimen in the evening appears to augment some markers of hypertrophic potential, with elevated IGFBP-3, suppressed cortisol and a superior cellular environment. Further investigation, to further elucidate the time course of peak anabolic signalling in morning vs evening training conditions, are timely

    Krill Excretion Boosts Microbial Activity in the Southern Ocean

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    Antarctic krill are known to release large amounts of inorganic and organic nutrients to the water column. Here we test the role of krill excretion of dissolved products in stimulating heterotrophic bacteria on the basis of three experiments where ammonium and organic excretory products released by krill were added to bacterial assemblages, free of grazers. Our results demonstrate that the addition of krill excretion products (but not of ammonium alone), at levels expected in krill swarms, greatly stimulates bacteria resulting in an order-of-magnitude increase in growth and production. Furthermore, they suggest that bacterial growth rate in the Southern Ocean is suppressed well below their potential by resource limitation. Enhanced bacterial activity in the presence of krill, which are major sources of DOC in the Southern Ocean, would further increase recycling processes associated with krill activity, resulting in highly efficient krill-bacterial recycling that should be conducive to stimulating periods of high primary productivity in the Southern Ocean.This research is a contribution to projects ICEPOS (REN2002-04165-CO3-O2) and ATOS (POL2006-00550/CTM), funded by the Spanish Ministry of Science and Innovation

    Caffeine Ingestion Reverses the Circadian Rhythm Effects on Neuromuscular Performance in Highly Resistance-Trained Men

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    Purpose: To investigate whether caffeine ingestion counteracts the morning reduction in neuromuscular performance associated with the circadian rhythm pattern. Methods: Twelve highly resistance-trained men underwent a battery of neuromuscular tests under three different conditions; i) morning (10:00 a.m.) with caffeine ingestion (i.e., 3 mg kg 21; AMCAFF trial); ii) morning (10:00 a.m.) with placebo ingestion (AMPLAC trial); and iii) afternoon (18:00 p.m.) with placebo ingestion (PMPLAC trial). A randomized, doubleblind, crossover, placebo controlled experimental design was used, with all subjects serving as their own controls. The neuromuscular test battery consisted in the measurement of bar displacement velocity during free-weight full-squat (SQ) and bench press (BP) exercises against loads that elicit maximum strength (75 % 1RM load) and muscle power adaptations (1 m s 21 load). Isometric maximum voluntary contraction (MVCLEG) and isometric electrically evoked strength of the right knee (EVOK LEG) were measured to identify caffeine’s action mechanisms. Steroid hormone levels (serum testosterone, cortisol and growth hormone) were evaluated at the beginning of each trial (PRE). In addition, plasma norepinephrine (NE) and epinephrine were measured PRE and at the end of each trial following a standardized intense (85 % 1RM) 6 repetitions bout of SQ (POST). Results: In the PM PLAC trial, dynamic muscle strength and power output were significantly enhanced compared with AM PLA

    Water quality and planktonic microbial assemblages of isolated wetlands in an agricultural landscape

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    Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Wetlands 31 (2011): 885-894, doi:10.1007/s13157-011-0203-6.Wetlands provide ecosystem services including flood protection, water quality enhancement, food chain support, carbon sequestration, and support regional biodiversity. Wetlands occur in human-altered landscapes, and the ongoing ability of these wetlands to provide ecosystem services is lacking. Additionally, the apparent lack of connection of some wetlands, termed geographically isolated, to permanent waters has resulted in little regulatory recognition. We examined the influence of intensive agriculture on water quality and planktonic microbial assemblages of intermittently inundated wetlands. We sampled 10 reference and 10 agriculturally altered wetlands in the Gulf Coastal Plain of Georgia. Water quality measures included pH, alkalinity, dissolved organic carbon, nutrients (nitrate, ammonium, and phosphate), and filterable solids (dry mass and ash-free dry mass). We measured abundance and relative size distribution of the planktonic microbial assemblage (< 45 Όm) using flow cytometry. Water quality in agricultural wetlands was characterized by elevated nutrients, pH, and suspended solids. Autotrophic microbial cells were largely absent from both wetland types. Heterotrophic microbial abundance was influenced by nutrients and suspended matter concentration. Agriculture caused changes in microbial assemblages forming the base of wetland food webs. Yet, these wetlands potentially support important ecological services in a highly altered landscape.Funding was provided by the Joseph W. Jones Ecological Research Center.2012-07-2
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