bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacokinetics of peginterferon alfa‐2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C
Authors: Brennan B. J. , Morcos P. N. , Wang K. , Blotner S. D. , Morrison R. , Hagedorn C. H. , Marbury T. C. , Sulkowski M. , Grippo J. F. 
Published: April 2012

SummaryBackgroundAmongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa‐2a (PEG‐IFN alfa‐2a) and ribavirin.AimTo evaluate the pharmacokinetics (PK) of PEG‐IFN alfa‐2a and ribavirin among these three groups.MethodsForty‐seven patients with genotype 1 CHC (17 African Americans, 14 Hispanics and 16 Caucasians) received 8 weeks of PEG‐IFN alfa‐2a (180 &g/week) and ribavirin (1000 or 1200 mg/day). PEG‐IFN alfa‐2a serum concentrations and ribavirin plasma concentrations were measured following the first dose and at week 8. Pharmacokinetic parameters (Cmax, Tmax, AUC, CL/F) were estimated using noncompartmental methods.ResultsThere was no difference in the pharmacokinetic parameters for PEG‐IFN alfa‐2a following single‐dose or steady‐state administration between African American or Hispanic patients compared with Caucasian patients. Ribavirin pharmacokinetic parameters were similar between Hispanic and Caucasian patients for single‐dose and steady‐state administration. The single‐dose Cmax was 33% lower (P < 0.05) in African American compared with Caucasian patients. Other ribavirin single‐dose and steady‐state pharmacokinetic parameters were slightly decreased (approximately 20% lower) in African American patients, but were not considered clinically meaningful.ConclusionsNo differences were observed in PEG‐IFN alfa‐2a pharmacokinetic parameters between African American or Hispanic patients compared with Caucasian patients. For ribavirin, no differences were observed in pharmacokinetic parameters between Hispanic and Caucasian patients. While a trend towards increased ribavirin clearance and decreased exposure was observed in African American patients vs. Caucasian patients, the differences were small and not considered clinically meaningful (Clinical Trial Number: NP17354).
Methotrexate for psoriasiform lesions associated with anti‐tumour necrosis factor therapy in inflammatory bowel disease
Authors: Buisson A. , Cuny J.‐F. , Barbaud A. , Schmutz J.‐L. , Bigard M.‐A. , Guéant J.‐L. , Peyrin‐Biroulet L. 
Published: April 2012

SummaryBackgroundPsoriasiform lesions associated with anti‐tumour necrosis factor (TNF) therapy are frequent in patients with inflammatory bowel disease (IBD). While methotrexate is the most frequently used systemic treatment for psoriasis, its efficacy for psoriasiform lesions related to anti‐TNF therapy remains unknown.AimsTo assess the efficacy of methotrexate for psoriasiform lesions associated with anti‐TNF therapy refractory to topical therapy in IBD patients.MethodsThe charts of eight patients from the Nancy IBD cohort who developed psoriasiform lesions on anti‐TNF therapy were reviewed. Clinical response was defined as a decrease of more than 50% in the lesions covering surface. All patients were followed up by the same experienced dermatologist.ResultsEight women (seven Crohn's disease) were followed up for a median duration of 29 months (range, 20–45). Of the eight patients receiving methotrexate, three were primary responders without discontinuation of anti‐TNF agents. Only one patient had a sustained response at final follow‐up and was able to continue both methotrexate and anti‐TNF therapy. Of the two other primary responders, one patient had to discontinue anti‐TNF because of severe psoriasiform lesions, whereas the other one continued anti‐TNF therapy despite persistent skin lesions at final follow‐up. Among the five primary nonresponders, four patients had to stop anti‐TNF treatment due to disabling skin lesions.ConclusionMethotrexate does not appear effective in treating psoriasiform lesions associated with anti‐TNF therapy refractory to topical therapy in IBD.
Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects
Authors: Aul Raminder , Armstrong Jane , Duvoix Annelyse , Lomas David , Hayes Brian , Miller Bruce E. , Jagger Chris , Singh Dave 
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Neutrophilic airway inflammation is a feature of chronic obstructive pulmonary disease (COPD). Inhaled lipopolysaccharide (LPS) challenge in healthy non‐smokers has been used to assess the anti‐inflammatory effects of novel drugs on neutrophilic airway inflammation.WHAT THIS STUDY ADDS• We performed inhaled LPS challenge in smokers to study an inflammatory response in subjects who more closely resemble COPD patients. Inhaled LPS caused reproducible pulmonary inflammation in smokers, associated with changes in systemic biomarkers. Inhaled LPS appears to be a suitable model for studying exacerbations of COPD.AIMS Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFκB dependent cytokine production. We investigated LPS inhalation in healthy smokers as a model of COPD bacterial exacerbations. We studied safety, reproducibility, the translocation of the NFκB subunit p65 in sputum cells and changes in systemic biomarkers of inflammation.METHODS Twelve smokers inhaled 5 and 30 µg LPS and safety was monitored over 24 h. IL‐6, CRP, CCl‐18, SP‐D, CC‐16 and β‐defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 h. Sputum was induced at baseline, 6 and 24 h for cell counts and p65 expression. Repeated challenges were performed after a 2 week interval in 10 smokers.RESULTS LPS inhalation was well tolerated. Significant increases occurred in sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 h after 30 µg which was reproducible, ri (intraclass correlation coefficient) = 0.88. LPS increased sputum cell nuclear p65 translocation and phospho‐p65 expression. All of the serum biomarkers increased following challenge but with different temporal patterns.DISCUSSION Inhaled LPS challenge in smokers causes pulmonary and systemic inflammation that involves NFκB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD.
Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE)
Authors: Styles Lori , Wager Carrie G. , Labotka Richard J. , Smith‐Whitley Kim , Thompson Alexis A. , Lane Peter A. , McMahon Lillian E. C. , Miller Robin , Roseff Susan D. , Iyer Rathi V. , Hsu Lewis L. , Castro Oswaldo L. , Ataga Kenneth I. , Onyekwere Onyinye , Okam Maureen , Bellevue Rita , Miller Scott T. ,   for the Sickle Cell Disease Clinical Research Network (SCDCRN)
Published: April 2012

SummaryAcute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre‐emptive therapy in high‐risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two‐thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.
‘I think I do have strategies’: lawyers' approaches to parent engagement in care proceedings
Authors: Masson Judith 
Published: April 2012

ABSTRACTThis paper examines the issue of parental engagement where children's services have brought court proceedings to protect children, from the perspective of specialist lawyers who represent parents. It draws on an in‐depth, qualitative study of parents' representation conducted between 2008 and 2010. Parental non‐co‐operation with children's services is a common feature in these cases. Lawyers are partisans with duties to follow clients' instructions. They seek to build a trusting relationship and keep clients engaged in the process by giving advice, taking instructions and providing emotional support. Lawyers accept that parents have an absolute right to contest but use their power and authority to encourage their most vulnerable clients to concede. They are largely successful in keeping clients engaged in proceedings but parents rarely make the necessary changes in parenting.
Making the developmental system work better for children: lessons learned implementing an innovative programme
Authors: Branch Sara , Homel Ross , Freiberg Kate 
Published: April 2012

ABSTRACTPathways to Prevention is an early prevention project founded on developmental systems theory operating through a schools‐community agency‐university partnership in a socially disadvantaged area of Brisbane. Circles of Care is a Pathways programme also implemented on a small scale by the same agency in a regional city. The Circles programme is designed to strengthen connections between schools, families and community services, and harmonize activities in these settings by surrounding children with identified needs with a supportive group of adults. A Circle, which includes at least the child, parent(s), teacher and agency staff, sets goals, mobilizes resources for the child, family and school, and monitors progress. The client is conceptualized not as the child but as a dysfunctional developmental system, with better outcomes for children as the ultimate goal. Qualitative evaluation at the two sites showed that while Circles worked well at the level of practical support and relationship building and did achieve good child outcomes, its capacity to achieve collaborative practice and strengthen system relations was limited by entrenched organizational structures and cultures. However, one site, with more support for collaboration across organizational boundaries, suggested that system alignment is achievable on a larger scale with vision and leadership for organizational reform.
Resettlement challenges faced by refugee claimant families in Montreal: lack of access to child care
Authors: Morantz Gillian , Rousseau Cécile , Banerji Anna , Martin Carolina , Heymann Jody 
Published: April 2012

ABSTRACTAdult refugee claimants experience several well‐documented post‐migratory challenges. Little is known about the resettlement process for refugee claimant families with children. This study reports on 75 open‐ended, in‐depth interviews with refugee claimant families in Montreal about their resettlement challenges and their proposed solutions to them. These interviews were conducted with 33 dyads and triads of children and parents attending a paediatric hospital. Experiences accessing formal and informal child care in Montreal were addressed. Subsequently, a comparative policy analysis was conducted on residency eligibility criteria for child care subsidization. Twenty‐eight out of 39 parents (73%) report a lack of informal or formal child care and 15 out of 33 families (39%) propose improving access to formal child care services. They describe a lack of informal child care as a result of reduced social networks, and affordability as a barrier to formal child care services. Refugee claimants are not eligible for subsidized child care in Quebec. A comparative policy analysis within Canada and comparable countries reveals that this situation is not unique to Quebec. However, most provinces and European countries offer child care subsidies to refugee claimants. Refugee claimants should qualify for child care subsidies. Social workers and community organizations should consider their clients' child care needs in designing programmes and services.
Resting egg banks can facilitate recovery of zooplankton communities after extended exposure to saline conditions
Authors: NIELSEN DARYL L. , SMITH DANIELLE , PETRIE ROCHELLE 
Published: April 2012

Summary1. Salinisation has had a major effect on the diversity of biota associated with freshwater wetlands. However, there is no information available about whether elements of the biotic communities would be able to recover if the concentration of salts within secondarily salinised wetlands was lowered to levels more typical of freshwater wetlands.2. We tested the hypothesis that dormant eggs of zooplankton are able to persist in wetlands with elevated salinities for extended periods of time by using zooplankton communities that had developed in mesocosms exposed to either salt concentrations of 13 500 mg L−1 or freshwater (<300 mg L−1) for a period of 22 months. We measured the response of the zooplankton community as concentration was reduced along a gradient of decreasing salinity from 13 500 mg L−1 to freshwater.3. In the freshwater mesocosms, the zooplankton community was abundant and taxon rich. In comparison at the start of the experiment in the high salinity mesocosms, the zooplankton community had low abundances and very few taxa. Numbers remained low in these mesocosms until salinity was reduced to <2500 mg L−1. Below this, there was a rapid increase in the abundance, and richness of zooplankton and communities became similar to the communities in the freshwater mesocosms.4. These results indicate that dormant eggs of zooplankton are able to persist in wetlands exposed to high salinity levels for up to 22 months and provide a means for zooplankton communities to rapidly respond once a wetland returns to freshwater.5. It is likely that if the underlying causes of secondary salinisation in wetlands are addressed, it will be possible to undertake restoration activities that allow the rapid return of some components of their biotic communities.
Chlorhexidine, ethanol, lipopolysaccharide and nicotine do not enhance the cytotoxicity of a calcium hydroxide pulp capping material
Authors: Wheater M. A. , Falvo J. , Ruiz F. , Byars M. 
Published: April 2012

Wheater MA, Falvo J, Ruiz F, Byars M. Chlorhexidine, ethanol, lipopolysaccharide and nicotine do not enhance the cytotoxicity of a calcium hydroxide pulp capping material. International Endodontic Journal, 45, 989–995, 2012.AbstractAim  To determine whether cells pre‐stressed by known cytotoxic or inflammatory agents are more susceptible to the deleterious effects of a calcium hydroxide formulation used in pulp capping.Methodology  Adult human dermal fibroblasts were treated for 48 h with 0.001% chlorhexidine, 0.2% ethanol, 5 μg mL−1Escherichia coli lipopolysaccharide (LPS) or 0.05 mmol L−1 nicotine. Cells were subsequently treated with the soluble materials extracted from Dycal pellets for an additional 24 h. Controls included cells cultured in medium only and cells exposed to Dycal only. Cytotoxicity was measured using colorimetric MTT, WST and secreted lactate dehydrogenase assays. In addition, mitotic activity was evaluated using a colorimetric histone H3 phosphorylation assay. Data were statistically analysed using anova with Tukey’s multiple comparison post‐test and significance at P ≤ 0.05.Results  For all assays, measured values for cells treated with chlorhexidine, ethanol, LPS or nicotine plus the soluble materials extracted from Dycal pellets were significantly lower compared to control (P < 0.05) for all comparisons between experimental conditions. However, between treatments and for comparisons of treatments with Dycal, there were no differences observed for any assay.Conclusions  Calcium hydroxide in a formulation used in dental clinical procedures is highly cytotoxic to cultured cells, as evidenced by several cellular assays. However, other known toxic agents, including chlorhexidine, ethanol, bacterial LPS and nicotine, do not appear to function synergistically to increase the deleterious cellular effects of the calcium hydroxide in an in vitro model of cytotoxicity.
Rapid environmental degradation in a subarctic ecosystem influences resource use of a keystone avian herbivore
Authors: Winiarski Kristopher J. , McWilliams Scott R. , Rockwell Robert F. 
Published: April 2012

Summary1. Environmental degradation can change resource use strategies of animals and thereby affect survival and fitness. Arctic herbivores may be especially susceptible to the effects of such environmental change because their rapid growth rates demand high‐quality forage, which may be limited as environmental conditions deteriorate. We studied the consequences of a trophic cascade, driven by Lesser Snow Goose (Chen caerulescens caerulescens) overgrazing on the south‐west coast of Hudson Bay, Canada, which has caused tidal marsh (TM) degradation and the reduction in high‐quality forage plants, on gosling growth and resource use.2. We compared resource use and body size of goslings that inhabited tidal and freshwater marsh (FM) to determine how current foraging strategies influence growth and to test the hypothesis that during early growth goslings require and so consume high‐quality TM plants, but that during later growth they may switch to foraging in lower‐quality FM.3. To investigate gosling resource use throughout growth, we measured once a week for 28 days the body size of goslings as well as stable isotope ratios (δ34S, δ15N and δ13C) in multiple tissues of goslings that were collected from both TM and nearby FM. We also measured the stable isotope ratios in forage plants sampled along transects and from gosling foreguts. We used an isotope‐mixing model to determine the contribution of FM plants to gosling tissues.4. Contrary to the proposed hypothesis, goslings inhabiting FM or TM primarily consumed FM plants during early growth. Furthermore, goslings that foraged extensively in FM had similar growth rates and grew to a similar size and body mass, as goslings that foraged in the degraded TM. However, goslings that currently inhabit freshwater or TM were significantly smaller than goslings that inhabited TM in the 1980s prior to habitat degradation.5. Consequences of smaller overall body size include decreased survival and fecundity for arctic‐nesting geese. The ability of phenotypically plastic responses to sustain persistence is limited by reaction norms and the extent of environmental change. Current research is assessing whether those limits have been reached in this system.
Impact of landscape alteration and invasions on pollinators: a meta‐analysis
Authors: Montero‐Castaño Ana , Vilà Montserrat 
Published: April 2012

Summary1. Alterations in land use and biological invasions are two major components of global change that threaten biodiversity. There is high concern about their impact on pollinators and the pollination services they provide. However, the growing literature shows different, even contradictory results.2. We present a global meta‐analysis of 58 publications reporting 143 studies (37 on landscape alteration and 21 on biological invasions) to assess the extent to which these components affect pollinators, and whether taxonomic and ecosystem‐type differences in pollinator responses occur. We also quantified which component of landscape alteration had the largest effect on pollinators and assessed whether animal invasions differ from plant invasions in their effect on native pollinators.3. Habitat alteration and invasions affected pollinators to the same magnitude by decreasing visitation rates. Vertebrates in altered landscapes and insects (excluding bees) in invaded areas were the most affected pollinator taxa.4. Pollinator abundance was more reduced in altered forest ecosystems than in altered grasslands; while the reverse pattern was found for pollinator richness. However, the response of pollinators to invasions was independent of ecosystem type.5. Disturbance of the surrounding matrix was more important in decreasing pollinator visitation rates than fragment size.6. Invasive animals seemed to have a more consistent negative effect on visitation rates than invasive plants.7. Synthesis. Our study highlights that different components of global change have similar negative outcomes on pollination patterns, but that responses of pollinators vary among taxa and ecosystem types, as well as the attributes of landscape alteration considered and whether the invader is an animal or a plant.
Forest fragmentation genetics in a formerly widespread island endemic tree: Vateriopsis seychellarum (Dipterocarpaceae)
Authors: FINGER A. , KETTLE C. J. , KAISER‐BUNBURY C. N. , VALENTIN T. , MOUGAL J. , GHAZOUL J. 
Published: April 2012

AbstractHabitat fragmentation and changed land use have seriously reduced population size in many tropical forest tree species. Formerly widespread species with limited gene flow may be particularly vulnerable to the negative genetic effects of forest fragmentation and small population size. Vateriopsis seychellarum (Dipterocarpaceae) is a formerly widespread canopy tree of the Seychelles, but is now reduced to 132 adult individuals distributed in eleven sites. Using ten microsatellite loci, a genetic inventory of all adult trees and a sample of 317 progeny, we demonstrate that despite its restricted range, overall genetic diversity was relatively high (HE: 0.56). The juvenile cohort, however, had significantly lower allelic richness (adults RS: 3.91; juveniles RS: 2.83) and observed heterozygosity than adult trees (adults HO: 0.62; juveniles HO: 0.48). Rare alleles were fewer and kinship between individuals was stronger in juveniles. Significant fine‐scale spatial genetic structure was observed in remnant adults, and parentage analysis indicated that more than 90% of sampled progeny disperse <25 m and pollen dispersed <50 m. The molecular data confirmed that two populations were derived entirely from self‐fertilized offspring from a single surviving mother tree. These populations produce viable offspring. Despite this extreme genetic bottleneck, self‐compatibility may provide V. seychellarum with some resistance to the genetic consequences of habitat fragmentation, at least in the short term. We discuss our findings in the context of other rare and threatened dipterocarp species which are vulnerable to miss‐management of genetic resources and population fragmentation.