bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta‐analysis of hepatitis C seroconversion in relation to shared syringes and drug preparation equipment
Authors: Pouget Enrique R. , Hagan Holly , Des Jarlais Don C. 
Published: December 2011

ABSTRACTAims  We conducted a systematic review of studies reporting seroincidence of hepatitis C infection (HCV) in relation to shared syringes and drug preparation equipment among injection drug users (IDUs). We identified published and unpublished studies that met inclusion criteria.Design  We estimated the relative contributions of shared syringes and drug preparation equipment to HCV transmission using random‐effects meta‐analysis, and analyzed potential sources of heterogeneity of effects among studies.Findings  Syringe sharing was associated with HCV seroconversion [pooled risk ratio (PRR) = 1.94, 95% confidence interval (CI) 1.53, 2.46], as was sharing drug preparation containers (PRR = 2.42, 95% CI 1.89, 3.10), filters (PRR = 2.61, 95% CI 1.91, 3.56), rinse water (PRR = 1.98, 95% CI 1.54, 2.56), combinations of this equipment (PRR = 2.24, 95% CI 1.28, 3.93) and ‘backloading’, a syringe‐mediated form of sharing prepared drugs (PRR = 1.86, 95% CI 1.41, 2.44). Meta‐regression results showed that the association between syringe sharing and seroconversion was modified by HCV seroprevalence in the IDU populations.Conclusions  The risk of hepatitis C infection through shared syringes is dependent upon hepatitis C infection seroprevalence in the population. The risk of hepatitis C infection through shared drug preparation equipment is similar to that of shared syringes. Because the infection status of sharing partners is often unknown, it is important for injection drug users to consistently avoid sharing unsterile equipment used to prepare, divide or inject drugs and avoid backloading with an unsterile syringe.
Increased incidence of QT interval prolongation in a population receiving lower doses of methadone maintenance therapy
Authors: Roy Andrew K. , McCarthy Catherine , Kiernan Gareth , McGorrian Catherine , Keenan Eamon , Mahon Niall G. , Sweeney Brion 
Published: December 2011

ABSTRACTAims  The aim of this study was to investigate the frequency of corrected QT interval (QTc) prolongation in a methadone maintenance therapy (MMT) population, and to examine potential associations between this QTc interval and methadone dose as well as concurrent use of opiates, cocaine and benzodiazepines.Design  Cross‐sectional study of patients attending a specialist drug treatment clinic from July 2008 to January 2009.Setting  Single‐centre inner‐city specialist drug treatment clinic, Ireland.Participants  A total of 180 patients on stable MMT attending for daily methadone doses, over a 6‐month period, where a total of 376 patients were attending during the study period.Measurements  All patients agreeing to participate in the study underwent 12‐lead electrocardiograms and QTc analysis, as well as analysis of urine toxicology screen results for opiates, benzodiazepines and cocaine. ECGs were carried out prior to methadone dose being received, regardless of time of day (trough ECG).Findings  The average age was 32.6 ± 7.1 years, with mean [standard deviation (SD)] methadone dose 80.4 ± 27.5 mg. The mean (SD) QTc was 420.9 ± 21.1 ms, range 368–495 ms. Patients who had a positive toxicology screen for opiates were receiving significantly lower doses of methadone (77.8 ± 23.5 mg versus 85.0 ± 21.4 mg, P = 0.04). No significant association was noted between QTc interval prolongation and presence of cocaine metabolites in the urine (P = 0.13) or methadone dose (P = 0.33). 8.8% of patients had evidence of prolonged QTc interval (8.3% male QTc ≥ 450 ms and 0.5% female QTc ≥ 470 ms), with 11.1% (n = 20) having QTc intervals > 450 ms.Conclusions  Drug‐induced corrected QT interval prolongation is evident (ranging from 8.8–11.1%, depending on definition applied) in patients receiving relatively low daily doses of methadone therapy, with no evidence of a dose–response relationship. The presence of cocaine metabolites in urine does not appear to be associated with increased corrected QT interval. Increased awareness of cardiac safety guidelines, including relevant clinical and family history, baseline and trough dose ECG monitoring, should be incorporated into methadone maintenance therapy protocols.
Neuroprotective effects of a new skin care formulation following ultraviolet exposure
Authors: Fonseca B. L. , dos Santos B. C. , Martins P. , Bonorino C. , Corte T. W. F. , da Silva V. D. , Bauer M. E. 
Published: December 2011

AbstractBackground:  Chronic ultraviolet (UV) exposure is a major environmental factor involved in extrinsic skin ageing (photo‐ageing). Skin nerve fibres are significantly reduced in number following UV irradiation and new skincare compounds with neuroprotective effects are thus highly warranted.Objectives:  We developed a new skincare formulation from a plant extract and evaluated its neuroprotective effects of ex vivo UV irradiation.Materials and methods:  The new skincare emulsion was formulated from Echinacea purpurea extract and was enriched with antioxidants (patent no. PROV020110087075). Skin samples were obtained from 20 healthy patients enrolled for plastic surgery and were immediately treated with placebo (SPF 15) or test emulsions. Skin samples were exposed to UVA and UVB for 60 min. Nerve fibres were identified by immunofluorescence using a monoclonal antibody, anti‐human CD56. Cell damage was quantified by image analysis.Results:  UVA and UVB significantly reduced (40–60%) densities of nerve endings in control samples treated with placebo (P < 0.001). Samples treated with test emulsion completely blocked UV‐related effects on skin nerve endings. These neuroprotective effects were similarly observed regardless of age or tissue analysed (breast versus abdomen).Conclusions:  Our new skincare formulation obtained from E. purpurea provides important neuroprotective effects of UV irradiation and could be used together with SPFs to prevent chronic deleterious effects of solar exposure.
Twin studies as a model for exploring the aetiology of autoimmune thyroid disease
Authors: Brix Thomas Heiberg , Hegedüs Laszlo 
Published: December 2011

SummaryTwins are an important resource for evaluating the relative contribution of genetic and environmental factors in determining a phenotype. During the last decades, a number of twin studies have investigated the aetiology of several phenotypes related to thyroid autoimmunity. Taken together, these studies have provided valid and unbiased information regarding the influence of genetic and environmental factors in the aetiology of autoimmune thyroid disease (AITD). The comparison of concordance rates between monozygotic (MZ) and dizygotic twins provides irrefutable evidence of a genetic component, and biometric twin modelling shows that approximately 75% of the total phenotypic variance in AITD is because of genetic effects. On the other hand, the lack of complete concordance in MZ twin pairs is proof of environmental and/or epigenetic factors also playing an important role. The impact of environmental triggers such as cigarette smoking, birth characteristics, infection with Yersinia enterocolitica, microchimerism and degree of X chromosome inactivation (XCI) has been evaluated by investigating AITD discordant twin pairs. These studies indicate that smoking, Y. enterocolitica infection and skewed XCI may be causally associated with clinically overt AITD, but not with the presence of thyroid autoantibodies in euthyroid subjects. Microchimerism, but not birth weight, might play a role in AITD. Twin studies offer several features that uniquely enhance our ability to localize genes and understand their function. Future twin studies should incorporate information on genetic, epigenetic and environmental variation thereby enhancing our ability to quantify the precise effect of specific risk factors.
Lipoprotein‐associated phospholipase A2 and outcome in patients with type 2 diabetes on haemodialysis
Authors: Winkler Karl , Hoffmann Michael M. , Krane Vera , Drechsler Christiane , Wanner Christoph ,   for the German Diabetes and Dialysis Study Investigators
Published: December 2011

Eur J Clin Invest 2012; 42 (7): 693–701AbstractBackground  Lipoprotein‐associated phospholipase A2 (LpPLA2) is a lipoprotein‐bound enzyme involved in inflammation and atherosclerosis. In a post hoc analysis of a controlled trial with atorvastatin in patients with type 2 diabetes (T2D) on haemodialysis, we examined the association between baseline and change by measuring baseline LpPLA2 activity on cardiovascular events (CVE) and mortality.Methods and results  LpPLA2 activity was available of 1202 patients at baseline and 6 months after randomisation from 1255 patients in the German Diabetes Dialysis Study. During the 4‐year follow‐up, 445 patients (37%) suffered from CVE and 583 patients (49%) died. The highest quartile of LpPLA2 activity (≥615 U/L) was associated with elevated risk for CVE [HR 1·35 (1·02–1·87); P = 0·035]. This association was mainly driven by the placebo group [HR 1·51 (1·01–2·25); P = 0·046]. Receiver‐operating characteristics analysis revealed that including LpPLA2 activity in an already adjusted model increased the area under the curve (AUC) for CVE from 0·586 (0·553–0·620) to 0·632 (0·599–0·664; P = 0·020) and for death from 0·704 (0·674–0·733) to 0·708 (0·679–0·737; P = 0·026). In atorvastatin‐treated patients, the decrease in LpPLA2 was associated with reduced fatal risk [HR per standard deviation 0·74 (0·62–0·90); P = 0·002], an effect not seen in the placebo group. In contrast, those patients in the placebo group presenting a > 25% decrease in LpPLA2 activity (n = 33) had a more than doubled risk of dying [HR 2·48 (1·56–3·95); P < 0·001].Conclusion  LpPLA2 activity is predictive for cardiovascular outcome and total mortality. Reducing LpPLA2 by atorvastatin was associated with reduced mortality in patients with T2D on haemodialysis.
Contrasting effects of an invasive crayfish (Procambarus clarkii) on two temperate stream communities
Authors: KLOSE KRISTIE , COOPER SCOTT D. 
Published: December 2011

Summary1. The effects of omnivorous exotic species on native communities are often difficult to predict because of the broad diets and behavioural flexibility of the omnivore, and the diverse abiotic and biotic characteristics of invaded systems. We investigated experimentally the effects of a gradient of density of the introduced, omnivorous red swamp crayfish Procambarus clarkii (Decapoda: Cambaridae) on two stream communities in southern California, U.S.A.2. The Ventura River is a clear, flowing stream with a cobble substratum, with abundant algae but low densities of large invertebrates, small herbivores and snails. The Santa Ynez River at the time of the study consisted of a series of drying pools underlain by sand, with abundant charophytes, large predatory invertebrates and herbivores, including snails.3. In the Ventura River, periphyton biomass and inorganic sediment decreased with increasing crayfish abundance, but in the Santa Ynez River, periphyton and sediment were unrelated to crayfish densities.4. In the Ventura River, the biomass and density of all benthic invertebrates combined, chironomids, micropredators, the meiofauna (chydorid cladocerans, copepods and ostracods), and specific predatory and herbivorous taxa, as well as taxon richness, were negatively related to crayfish density. In the Santa Ynez River, the biomass and average body size of benthic invertebrates, predatory invertebrates, herbivores and chironomids, but not total invertebrate density or taxon richness, were negatively related to crayfish density.5. Fewer large predatory invertebrates and snails (Physella gyrina) in both streams, and baetid mayflies in the Ventura River, were visible at night in channels where crayfish were abundant. Snails responded to crayfish by moving above the water line in the Santa Ynez River, but not in the Ventura River.6. We suggest that the same omnivore had different effects on these neighbouring streams because of crayfish predation on large invertebrates in the Santa Ynez River and the scarcity of such prey in the Ventura River, leading to increased crayfish grazing on periphyton, and reductions in periphyton‐associated invertebrates, in the Ventura River.
Pasture use and management strategies in the Ankole pastoral system in Uganda
Authors: Roschinsky R. , Mulindwa H. , Galukande E. , Wurzinger M. , Mpairwe D. , Okeyo A. M. , Sölkner J. 
Published: December 2011

AbstractThe Bahima ethnic group have been crossbreeding autochthonous Ankole with Holstein‐Friesian cattle. Separate herds (pure Ankole and crossbreds) are common. A survey was conducted to characterize pasture utilization and management in the Ankole region to gain a better understanding of current and emerging practices. Herds are largely grazed by continuous stocking although there are efforts to establish paddocks. Factors considered for pasture allocation to cattle genotypes were high‐quality feed, limited shrubs/weeds and close proximity to homestead for 80, 80 and 30% of farmers, respectively. Cross‐bred cattle were kept on medium/high‐quality, and Ankole cattle on medium/low‐quality pastures. Pastures for cross‐bred cattle yielded 0·17 t ha−1 more dry matter than pastures allocated to Ankole cattle. Crude protein (CP) content of Ankole pasture was significantly (P < 0·05) lower than CP of cross‐bred pasture (6·3% compared with 7·3%). Neutral detergent fibre content was similar (72·8% vs. 69·8%) for both pasture types. Farmers’ perceptions of indicator plant species were important for allocation of pasture. Hyparrhenia rufa, Brachiaria spp., Themeda triandra and Chloris gayana were identified as the preferred pasture species. Sporobolus pyramidalis and Cymbopogon afronardus were the most undesirable pasture species. Brachiaria spp. offers an opportunity for utilization as hay for dry season supplementation.
The endocrine disruptors dibutyl phthalate (DBP) and diethylstilbestrol (DES) influence Leydig cell regeneration following ethane dimethane sulphonate treatment of adult male rats
Authors: Heng K. , Anand‐Ivell R. , Teerds K. , Ivell R. 
Published: December 2011

SummaryThe manner by which endocrine‐disrupting xenobiotics, such as phthalates, can induce changes in the development of the male reproductive system still remains largely unknown. Herein, we have explored the application of ethane dimethane sulphonate (EDS) to eliminate adult‐type Leydig cells in the mature rat testis, leading to their regeneration from resident stem cells, as a novel system to investigate the effects of dibutyl phthalate (DBP) and diethylstilbestrol (DES) on adult‐type Leydig cell differentiation. The advantage of this model is that one can study adult‐type Leydig cell differentiation in vivo divorced from the concomitant endocrine development of puberty. In these preliminary studies, we show that both DBP and/or DES, given for 2 or 4 days following EDS application, indeed affect Leydig cell differentiation in the adult testis, largely by increasing early Leydig cell proliferation and possibly thereby delaying early differentiation. In particular, on day 27 post‐EDS, a time‐point when the differentiation trajectory appears to be most discriminating, we observe that both DBP and/or DES cause a fourfold increase in Leydig cell density, and a significant increase in the expression of the Leydig cell‐specific marker transcripts INSL3, LH receptor, Cyp17a1 and Cyp 11a1. In conclusion, both DBP and DES are able to affect adult‐type Leydig cells during their differentiation to cause a significant perturbation in their ultimate functional capacity.
Ecosystem CO2 starvation and terrestrial silicate weathering: mechanisms and global‐scale quantification during the late Miocene
Authors: Beerling David J. , Taylor Lyla L. , Bradshaw Catherine D. C. , Lunt Daniel J. , Valdes Paul J. , Banwart Steven A. , Pagani Mark , Leake Jonathan R. 
Published: December 2011

Summary1. The relative constancy of the lower limit on Earth’s atmospheric CO2 concentration ([CO2]a) during major tectonic episodes over the final 24 million years (Ma) of the Cenozoic is surprising because they are expected to draw‐down [CO2]a by enhancing chemical weathering and carbonate deposition on the seafloor. That [CO2]a did not drop to extremely low values suggests the existence of feedback mechanisms that slow silicate weathering as [CO2]a declines. One proposed mechanism is a negative feedback mediated through CO2 starvation of land plants in active orogenic regions compromising the efficiency of the primary carboxylating enzyme in C3 plants (Rubisco) and diminishing productivity and terrestrial weathering.2. The CO2 starvation hypothesis is developed further by identifying four key related mechanisms: decreasing net primary production leading to (i) decreasing below‐ground C allocation, reducing the surface area of contact between minerals and roots and mycorrhizal fungi and (ii) reduced demand for soil nutrients decreasing the active exudation of protons and organic acids by fine roots and mycorrhizas; (iii) lower carbon cost‐for‐nutrient benefits of arbuscular mycorrhizas (AM) favouring AM over ectomycorrhizal root–fungal symbioses, which are less effective at mineral weathering, and (iv) conversion of forest to C3 and C4 grassland arresting Ca leaching from soils.3. We evaluated the global importance of mechanisms 1 and 2 in silicate weathering under a changing late Miocene [CO2]a and climate using a process‐based model describing the effects of plants and mycorrhizal fungi on the biological proton cycle and soil chemistry. The model captures what we believe are the key processes controlling the pH of the mycorrhizosphere and includes numerical routines for calculating weathering rates on basalt and granite using simple yet rigorous equilibrium chemistry and rate laws.4. Our simulations indicate a reduction in the capacity of the terrestrial biosphere to weather continental silicate rocks by a factor of four in response to successively decreasing [CO2]a values (400, 280, 180 and 100 p.p.m.) and associated late Miocene (11.6–5.3 Ma) cooling. Marked reductions in terrestrial weathering could effectively limit biologically mediated long‐term carbon sequestration in marine sediments.5. These results support the idea of terrestrial vegetation acting as a negative feedback mechanism that counteracts substantial declines in [CO2]a linked to increased production of fresh weatherable minerals in warm, low‐latitude, active orogenic regions.
A forest structure model that determines crown layers and partitions growth and mortality rates for landscape‐scale applications of tropical forests
Authors: Bohlman Stephanie , Pacala Stephen 
Published: December 2011

Summary1. We present a model to quantify tropical forest structure and explain variance in dynamic rates (growth and mortality) that is computationally simple and can be applied to landscape‐scale forest inventory and, potentially, remote sensing‐derived data.2. The model is a modification of the perfect plasticity approximation (PPA) based on tree allometry, tree locations and sizes. The model quantifies crown area index (CAI) (number of crowns per unit ground area) and assigns trees to crown layers, which determines the expected number of crowns above each tree and thus its light environment.3. The structural model, parameterized and tested for the Barro Colorado Island, Panama 50‐ha forest dynamics plot using data from forest inventories and stereo aerial photographs, reproduces most canopy and understorey structural and dynamic properties. The PPA model worked as well or better than a computationally intensive, spatially explicit model. A single allometry for all trees worked equally well as functional group or species allometries. Models of growth and mortality were always improved by adding crown layers as defined by the PPA model.4. The mean CAI of the 50‐ha plot was 3.1 with low variance. The observed variance was lower than when tree locations were randomized, which drastically lowered the variance in tree density per plot, indicating that there are regulating forces towards a small range of crown area indices.5. Synthesis. A number of simplifying characteristics in structure were uncovered with the PPA structural model applied to a tropical forest: species allometries were not needed despite the high species diversity in the forest; the model worked on a range of plot sizes; and the variance in CAI was surprisingly low, suggesting regulatory mechanisms. The PPA structural model can be used to develop a fully dynamic simulation model for tropical forests. The ability of the simulation model to predict temporal changes in landscape patterns of biomass, dynamic rates, and species and/or functional group composition will provide validation for the partitioning of dynamic rates by crown layers in the PPA structural model.
Realist methods in medical education research: what are they and what can they contribute?
Authors: Wong Geoff , Greenhalgh Trisha , Westhorp Gill , Pawson Ray 
Published: December 2011

Medical Education 2012: 46: 89–96Context  Education is a complex intervention which produces different outcomes in different circumstances. Education researchers have long recognised the need to supplement experimental studies of efficacy with a broader range of study designs that will help to unpack the ‘how’ and ‘why’ questions and illuminate the many, varied and interdependent mechanisms by which interventions may work (or fail to work) in different contexts.Methods  One promising approach is realist evaluation, which seeks to establish what works, for whom, in what circumstances, in what respects, to what extent, and why. This paper introduces the realist approach and explains why it is particularly suited to education research. It gives a brief introduction to the philosophical assumptions underlying realist methods and outlines key principles of realist evaluation (designed for empirical studies) and realist review (the application of realist methods to secondary research).Discussion  The paper warns that realist approaches are not a panacea and lists the circumstances in which they are likely to be particularly useful.
History and practice of competency‐based assessment
Authors: Lurie Stephen J. 
Published: December 2011

Medical Education 2012: 46: 49–57Context  In response to historical trends in expectations of doctors, the goals of medical education are increasingly framed in terms of global competencies. The language of these competencies has tended to adopt a prescriptive, rather than descriptive, approach. However, despite widespread agreement on the importance of competency‐based education and more than two decades of study, this effort has not generated a dependable set of assessment tools.Discussion  Because models of competency are legislated, rather than shaped by scholarly consideration of empirical data, it is unlikely that such models directly reflect actual human behaviour. Efforts to measure clinical behaviours could benefit from increased clarity in three related conceptual areas. Firstly, the language of educational constructs should be framed in terms of data‐based hypotheses, rather than in terms of intuitively plausible abilities. Secondly, these constructs should be specified in terms of the situations to which they are relevant, rather than as global personal characteristics. Finally, the resources required to measure these constructs should be rigorously established because a common resource‐based metric would allow for rational selection of assessment methods. Specific methods to establish each of these objectives are discussed.Conclusions  The political process of negotiating educational objectives should not be confused with the scientific work of establishing coherent and interpretable patterns of behaviour. Although the two activities can complement one another, each has its own distinct methods and style of discourse. It is thus critical to maintain boundaries between these two approaches to defining professional performance.