bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing drug–drug interactions with new direct‐acting antiviral agents in chronic hepatitis C
Authors: Talavera Pons Sarah , Boyer Anne , Lamblin Geraldine , Chennell Philip , Châtenet François‐Thibault , Nicolas Carine , Sautou Valérie , Abergel Armand 
Published: August 2016

Several direct‐acting antiviral agents (DAAs) have marketing authorization in Europe and in the USA and have changed the landscape of hepatitis C treatment: each DAA has its own metabolism and drug–drug interactions (DDIs), and managing them is a challenge. To compile the pharmacokinetics and DDI data of the new DAA and to provide a guide for management of DDI. An indexed MEDLINE search was conducted using the keywords: DAA, hepatitis C, simeprevir, daclatasvir, ledipasvir, sofosbuvir, 3D regimen (paritaprevir/ritonavir, ombitasvir, dasabuvir), DDI and pharmacokinetics. Data were also collected from hepatology, and infectious disease and clinical pharmacology conferences abstracts. Food can play a role in the absorption of DAAs. Most of the interactions are linked to metabolism (cytochrome P450‐3 A4 [CYP3A4]) or hepatic and/or intestinal transporters (organic anion‐transporting polypeptide and P‐glycoprotein [P‐gp]). To a lesser extent other pathways can be involved such as breast cancer resistance protein transporter or UDP‐glucuronosyltransferase metabolism. DDI are more likely to occur with 3D regimen, daclatasvir, simeprevir and ledipasvir, as they are all both substrates and inhibitors of P‐gp and/or CYP3A4, than with sofosbuvir. They can increase concentrations of coadministered drugs and their concentrations may be influenced by P‐gp or CYP3A4 inducers or inhibitors. Overdosage or low dosage can be encountered with potent inducers or inhibitors of CYP3A4 or drugs with a narrow therapeutic range. The key to interpret DDI data is a good understanding of the pharmacokinetic profiles of the drugs involved. Their ability to inhibit CYP450‐3A4 and transporters (hepatic and/or intestinal) can have significant clinical consequences.
The conformational IgE epitope profile of soya bean allergen Gly m 4
Authors: Husslik F. , Nürnberg J. , Seutter von Loetzen C. , Mews T. , Ballmer‐Weber B. K. , Kleine‐Tebbe J. , Treudler R. , Simon J.‐C. , Randow S. , Völker E. , Reuter A. , Rösch P. , Vieths S. , Holzhauser T. , Schiller D. 
Published: August 2016

SummaryBackgroundBirch pollen‐related soya allergy is mediated by Gly m 4. Conformational IgE epitopes of Gly m 4 are unknown.ObjectiveTo identify the IgE epitope profile of Gly m 4 in subjects with birch pollen‐related soya allergy utilizing an epitope library presented by Gly m 4‐type model proteins.MethodsSera from patients with (n = 26) and without (n = 19) allergy to soya as determined by oral provocation tests were studied. Specific IgE (Bet v 1/Gly m 4) was determined by ImmunoCAP. A library of 59 non‐allergenic Gly m 4‐type model proteins harbouring individual and multiple putative epitopes for IgE was tested in IgE binding assays. Primary, secondary and tertiary protein structures were assessed by mass spectrometry, circular dichroism and nuclear magnetic resonance spectroscopy.ResultsAll subjects were sensitized to Gly m 4 and Bet v 1. Allergen‐specific serum IgE levels ranged from 0.94 to > 100 kUA/L. The avidities of serum IgE were 5.06 ng (allergic) and 1.8 ng (tolerant) as determined by EC50 for IgE binding to Gly m 4. 96% (46/48) of the protein variants bound IgE. Model proteins had Gly m 4‐type conformation and individual IgE binding clustered in six major surface areas. Gly m 4‐specific IgE binding could be inhibited to up to 80% by model proteins harbouring individual IgE binding sites in an epitope‐wise equimolar fashion. Receiver operating curve analysis revealed an area under fitted curve of up to 0.88 for model proteins and 0.66 for Gly m 4.Conclusion and Clinical RelevanceSerum levels and avidity of Gly m 4‐specific IgE do not correlate with clinical reactivity to soya. Six IgE‐binding areas, represented by 23 amino acids, account for more than 80% of total IgE binding capacity of Gly m 4. Model proteins may be used for epitope‐resolved diagnosis to differentiate birch‐soya allergy from clinical tolerance.
Social capital as a key determinant of perceived benefits of community‐based marine protected areas
Authors: Diedrich Amy , Stoeckl Natalie , Gurney Georgina G. , Esparon Michelle , Pollnac Richard 
Published: August 2016

AbstractGlobally, marine protected areas (MPAs) have been relatively unsuccessful in meeting biodiversity objectives. To be effective, they require some alteration of people's use and access to marine resources, which they will resist if they do not perceive associated benefits. Stakeholders’ support is crucial to ecological success of MPAs, and their support is likely to depend on their capacity to adapt to and benefit from MPAs. We examined the influence of social adaptive capacity (SAC) on perceived benefits of MPAs in Siquijor, Philippines, in the Coral Triangle. This region has substantial biodiversity and a population of over 120 million people, many of them dependent on marine resources for food and income. The region has many MPAs, most of which are managed under decentralized governance systems. We collected survey data from 540 households in 19 villages with associated MPAs. We evaluated the influence of multiple SAC variables (e.g., occupational multiplicity and social capital) on perceived benefits with decision trees (CHAID) and qualitatively analyzed this relationship with respect to types and recipients of benefits. Our models revealed the key role of social capital, particularly trust in leadership, in influencing perceptions of benefits (χ2 = 14.762, p = 0.000). A path analysis revealed that perceptions of distributional equity were a key mechanism through which social capital affected perceived MPA benefits (root mean‐square error of approximation = 0.050). Building social capital and equity within communities could lead to more effective management of MPAs and thus to expenditure of fewer resources relative to, for example, regulation enforcement.
1,25 Dihydroxyvitamin D circulating levels, calcitriol administration, and incidence of acute rejection, CMV infection, and polyoma virus infection in renal transplant recipients
Authors: Moscarelli Luciano , Antognoli Giulia , Buti Elisa , Dervishi Egrina , Fani Filippo , Caroti Leonardo , Tsalouchos Aris , Romoli Elena , Ghiandai Giulia , Minetti Enrico 
Published: August 2016

AbstractObservation that 1,25‐Dihydroxyvitamin‐D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy‐proven acute rejection, CMV infection, BKV infection, with 1,25‐Dihydroxyvitamin‐D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25‐Dihydroxyvitamin‐D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus‐associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2‐D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2‐D3 circulating levels.
Treatment of Type 2 diabetes mellitus in Chongqing of China: unaffordable care for the poor
Authors: Long Q. , He M. , Tang X. , Allotey P. , Tang S. 
Published: August 2016

AbstractAimThis study aims to investigate the medical expenditure of people with Type 2 diabetes mellitus in Chongqing, China; to explore factors that contribute to the expenditure; and to examine the financial burden placed on households, particularly poor households.MethodsA cross sectional survey was conducted with a sample of people diagnosed with Type 2 diabetes mellitus in 2014. Of the 664 people eligible, 76% were interviewed. Descriptive statistics and log‐linear regression were used to examine respondents’ age, sex and level education, location of residence, income and type of health insurance associated with out‐of‐pocket expenditure on accessing diabetes mellitus care.ResultsIn a year, average out‐of‐pocket expenditure on the purchase of drugs from pharmacies and having outpatient care were US $333 and US $310, respectively. The average out‐of‐pocket expenditure on accessing inpatient care was 3.7 times (US $1159) that of accessing outpatient care. After adjusting for age and sex, out‐of‐pocket expenditure on diabetes care was significantly higher for people covered by the Urban Employee Basic Medical Insurance programme and those enrolled in the identified priority diseases reimbursement programme, which provided higher reimbursement rates for outpatient and (or) inpatient care. Out‐of‐pocket expenditures on the purchase of drugs from pharmacies, having outpatient and inpatient care, respectively, were 9.8%, 16.2% and 62.6% of annual household income in low‐income group.ConclusionEven with health insurance coverage, poor people with Type 2 diabetes mellitus suffered from significant financial hardship. This has significant implications for models of care and healthcare financing in China with the growing burden of diabetes.
Mass‐flowering crops dilute pollinator abundance in agricultural landscapes across Europe
Authors: Holzschuh Andrea , Dainese Matteo , González‐Varo Juan P. , Mudri‐Stojnić Sonja , Riedinger Verena , Rundlöf Maj , Scheper Jeroen , Wickens Jennifer B. , Wickens Victoria J. , Bommarco Riccardo , Kleijn David , Potts Simon G. , Roberts Stuart P. M. , Smith Henrik G. , Vilà Montserrat , Vujić Ante , Steffan‐Dewenter Ingolf 
Published: August 2016

AbstractMass‐flowering crops (MFCs) are increasingly cultivated and might influence pollinator communities in MFC fields and nearby semi‐natural habitats (SNHs). Across six European regions and 2 years, we assessed how landscape‐scale cover of MFCs affected pollinator densities in 408 MFC fields and adjacent SNHs. In MFC fields, densities of bumblebees, solitary bees, managed honeybees and hoverflies were negatively related to the cover of MFCs in the landscape. In SNHs, densities of bumblebees declined with increasing cover of MFCs but densities of honeybees increased. The densities of all pollinators were generally unrelated to the cover of SNHs in the landscape. Although MFC fields apparently attracted pollinators from SNHs, in landscapes with large areas of MFCs they became diluted. The resulting lower densities might negatively affect yields of pollinator‐dependent crops and the reproductive success of wild plants. An expansion of MFCs needs to be accompanied by pollinator‐supporting practices in agricultural landscapes.
Evolutionary response when selection and genetic variation covary across environments
Authors: Wood Corlett W. , Brodie Edmund D. 
Published: August 2016

AbstractAlthough models of evolution usually assume that the strength of selection on a trait and the expression of genetic variation in that trait are independent, whenever the same ecological factor impacts both parameters, a correlation between the two may arise that accelerates trait evolution in some environments and slows it in others. Here, we address the evolutionary consequences and ecological causes of a correlation between selection and expressed genetic variation. Using a simple analytical model, we show that the correlation has a modest effect on the mean evolutionary response and a large effect on its variance, increasing among‐population or among‐generation variation in the response when positive, and diminishing variation when negative. We performed a literature review to identify the ecological factors that influence selection and expressed genetic variation across traits. We found that some factors – temperature and competition – are unlikely to generate the correlation because they affected one parameter more than the other, and identified others – most notably, environmental novelty – that merit further investigation because little is known about their impact on one of the two parameters. We argue that the correlation between selection and genetic variation deserves attention alongside other factors that promote or constrain evolution in heterogeneous landscapes.
Teasing apart plant community responses to N enrichment: the roles of resource limitation, competition and soil microbes
Authors: Farrer Emily C. , Suding Katharine N. 
Published: August 2016

AbstractAlthough ecologists have documented the effects of nitrogen enrichment on productivity, diversity and species composition, we know little about the relative importance of the mechanisms driving these effects. We propose that distinct aspects of environmental change associated with N enrichment (resource limitation, asymmetric competition, and interactions with soil microbes) drive different aspects of plant response. We test this in greenhouse mesocosms, experimentally manipulating each factor across three ecosystems: tallgrass prairie, alpine tundra and desert grassland. We found that resource limitation controlled productivity responses to N enrichment in all systems. Asymmetric competition was responsible for diversity declines in two systems. Plant community composition was impacted by both asymmetric competition and altered soil microbes, with some contributions from resource limitation. Results suggest there may be generality in the mechanisms of plant community change with N enrichment. Understanding these links can help us better predict N response across a wide range of ecosystems.
Genomics advances the study of inbreeding depression in the wild
Authors: Kardos Marty , Taylor Helen R. , Ellegren Hans , Luikart Gordon , Allendorf Fred W. 
Published: August 2016

AbstractInbreeding depression (reduced fitness of individuals with related parents) has long been a major focus of ecology, evolution, and conservation biology. Despite decades of research, we still have a limited understanding of the strength, underlying genetic mechanisms, and demographic consequences of inbreeding depression in the wild. Studying inbreeding depression in natural populations has been hampered by the inability to precisely measure individual inbreeding. Fortunately, the rapidly increasing availability of high‐throughput sequencing data means it is now feasible to measure the inbreeding of any individual with high precision. Here, we review how genomic data are advancing our understanding of inbreeding depression in the wild. Recent results show that individual inbreeding and inbreeding depression can be measured more precisely with genomic data than via traditional pedigree analysis. Additionally, the availability of genomic data has made it possible to pinpoint loci with large effects contributing to inbreeding depression in wild populations, although this will continue to be a challenging task in many study systems due to low statistical power. Now that reliably measuring individual inbreeding is no longer a limitation, a major focus of future studies should be to more accurately quantify effects of inbreeding depression on population growth and viability.
Prediction of taxon occurrence: a test on taxon‐specific change point values of stream benthic invertebrates
Authors: Leps Moritz , Leisner Sabrina , Haase Peter , Sundermann Andrea 
Published: August 2016

Summary

Ecological thresholds represent abrupt species responses to minor changes in the environment. However, as aquatic organisms are frequently exposed to multiple stressors, prediction of taxon occurrence is challenging and often associated with much uncertainty. In this study, we analysed the response of stream benthic invertebrates to selected environmental gradients and determined the frequency and predictability of threshold responses.

Re‐analysis of taxon‐specific change point values for 213 riverine benthic invertebrate taxa and nine water quality variables showed that the predictive performance was acceptable for 30.4% and excellent for 9.6% of the total number of validated change points (n = 978). In total, 48.3% of the taxa that were predicted to occur (taxon presence predicted) and 67% of the taxa predicted not to occur (taxon absence predicted) were correct but with high variability across taxa and chemical variables. Predictive performance was the highest for stenoecious taxa and for certain chemical variables, such as ammonium nitrogen and the daytime dissolved oxygen concentration.

Responses to peak level concentrations of water quality variables were less threshold‐like compared with relationships with mean values. However, model predictions were equal for both of the approaches.

Successful prediction of taxon absence at stress levels beyond the change point values showed that the latter can well represent the upper limit of the taxon‐specific range of occurrence. Thus, change points are valuable for establishing and evaluating new water management tools, such as water quality criteria. By contrast, prediction of taxon presence at low levels of stress was associated with relatively high uncertainty, reflecting the limitation of taxon occurrence by stressors other than those investigated.
Effects of model assumptions and data quality on spatial cumulative human impact assessments
Authors: Stock Andy , Micheli Fiorenza 
Published: August 2016

AbstractAimMany studies have quantified and mapped cumulative human impacts on marine ecosystems. These maps are intended to inform management and planning, but uncertainty in them has not been studied in depth. This paper aims to: (1) quantify the uncertainty in cumulative impact maps and related spatial modelling results; (2) attribute this uncertainty to specific model assumptions and problems with data quality; (3) identify and test sound approaches to such analyses.LocationWe used the Baltic Sea and the Mediterranean and Black Seas as example regions. The methods and conclusions are relevant for human impact mapping anywhere.MethodsWe conducted computational experiments to test the effects of nine model assumptions and data quality problems (factors) on maps of human impact and related modelling results. The factors were implemented on the basis of a literature review. We quantified aggregate uncertainty using Monte Carlo simulations, and ranked the factors by their influence on modelling results using the elementary effects method. Both methods are well established and theoretically suitable for complex models, but had to be modified for application to spatial human impact models.ResultsSome, but not all, modelling results were robust. This contradicts previous studies that found only minor effects of the factors they tested. Of the nine factors tested here, eight had a considerable influence on at least one modelling result in at least one of the two study regions.Main conclusionsModel assumptions and data quality have larger aggregate effects on maps of human impact than found in previous analyses. These effects depend on the study region and the data that describe it. Future human impact mapping studies should thus include comprehensive uncertainty analyses. Computational experiments allow us to distinguish robust from less reliable modelling results and to prioritize improvements in models and data.
Introduction history, climatic suitability, native range size, species traits and their interactions explain establishment of Chinese woody species in Europe
Authors: Feng Yanhao , Maurel Noëlie , Wang Zhiheng , Ning Lei , Yu Fei‐Hai , van Kleunen Mark 
Published: August 2016

AbstractAimA major challenge in ecology is to understand how multiple causal factors, which may interact, drive success of non‐native plants in new ranges. In this study we addressed the role of introduction history, climatic suitability, native range size, species traits and their interactions in the establishment of Chinese woody species in Europe.LocationChina (native range), Europe (new range).MethodsWe tested whether establishment of 449 Chinese woody species in Europe was associated with residence time (time since earliest planting), planting frequency, climatic suitability, native range size and species traits. We also considered possible nonlinear effects and interactions among these variables. For the 38 species that have established in Europe, we further tested whether these variables and interactions explained their establishment in multiple European countries.ResultsEstablishment of the 449 species in Europe was positively associated with residence time, planting frequency and climatic suitability. Except residence time, these factors were also positively associated with establishment of the 38 species in multiple countries. None of the traits tested had statistically significant main effects on establishment in Europe, but, for the established species, longer flowering period and having compound leaves were positively associated with establishment in multiple countries. The positive association between establishment in Europe and residence time was stronger for evergreen than for deciduous species. In addition, evergreens, unlike deciduous species, showed a positive association between establishment in Europe and fruiting duration. Moreover, establishment in multiple countries was positively associated with planting frequency for species with compound leaves but not for species with simple leaves, and the association between the establishment and fruiting duration changed from negative to moderately positive as climatic suitability increased.Main conclusionsIntroduction history and climatic suitability explain most of the variation in establishment, and modulate the role of species traits, such as leaf retention, leaf type and fruiting duration.