bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescribing pattern of glucose lowering drugs in the United Kingdom in the last decade: a focus on the effects of safety warnings about rosiglitazone
Authors: Leal Ingrid , Romio Silvana A. , Schuemie Martijn , Oteri Alessandro , Sturkenboom Miriam , Trifirò Gianluca 
Published: July 2012

AimIn the last decade, new glucose lowering drugs (GLDs) have been launched, and also several warnings regarding their safety. The cardiovascular safety of thiazolidinediones (TZD) has been questioned. We analyzed the prescription pattern of GLDs from 2000 to November 2009 in the United Kingdom (UK) using the THIN database with special focus on the effects of the safety warnings about rosiglitazone issued in May 2007 and January 2008.MethodsAnnual prevalence and incidence of GLD prescriptions were measured. For TZD, the monthly prevalence and incidence of prescription were calculated from May 2006 to January 2009. The switching pattern around the FDA alert and the characteristics of subjects starting treatment with TZD before and after the alerts were observed.ResultsThe prevalence of prescriptions of GLDs increased during the 10 year period, metformin increasing more than three times. Rosiglitazone prevalence showed an increased trend until May 2007, (2.3/1000 person‐years) and decreased thereafter (January 2009: 1.1/1000 person‐years). The use of pioglitazone increased surpassing rosiglitazone from April 2008 onwards. The incidence of rosiglitazone use decreased sharply after May 2007 (0.8/1000 person‐years). The prevalence of use of other therapies remained rather stable from 2000 to 2007 but increased afterwards. After May 2007, rosiglitazone users were increasingly switched to pioglitazone. There was an increased proportion of new users of pioglitazone with cardiovascular risk after the alerts.ConclusionsThe prescription of GLDs in the UK has increased in the last decade. For TZDs, it changed after May 2007 as well as the characteristics of the subjects treated with them.
Pharmacokinetics of paracetamol and its metabolites in women at delivery and post‐partum
Authors: Kulo Aida , Peeters Mariska Y. , Allegaert Karel , Smits Anne , de Hoon Jan , Verbesselt Rene , Lewi Liesbeth , van de Velde Marc , Knibbe Catherijne A. J. 
Published: July 2012

AimA recent report on intravenous (i.v.) paracetamol pharmacokinetics (PK) showed a higher total clearance in women at delivery compared with non‐pregnant women. To describe the paracetamol metabolic and elimination routes involved in this increase in clearance, we performed a population PK analysis in women at delivery and post‐partum in which the different pathways were considered.MethodsPopulation PK parameters using non‐linear mixed effect modelling were estimated in a two‐period PK study in women to whom i.v. paracetamol (2 g loading dose followed by 1 g every 6 h up to 24 h) was administered immediately following Caesarean delivery and in a subgroup of the same women to whom single 2 g i.v.loading dose was administered 10–15 weeks post‐partum.ResultsPopulation PK analysis was performed based on 255 plasma and 71 urine samples collected in 39 women at delivery and in eight of these 39 women 12 weeks post‐partum. Total clearance was higher in women at delivery compared with 12th post‐partum week (21.1 vs. 11.7 l h−1) due to higher clearances to paracetamol glucuronide (11.6 vs. 4.76 l h−1), to oxidative metabolites (4.95 vs. 2.77 l h−1) and of unchanged paracetamol (1.15 vs. 0.75 l h−1). In contrast, there was no difference in clearance to paracetamol sulphate.ConclusionThe increased total paracetamol clearance at delivery is caused by a disproportional increase in glucuronidation clearance and a proportional increase in clearance of unchanged paracetamol and in oxidation clearance, of which the latter may potentially limit further dose increase in this patient group.
Antibody combination therapy targeting CD25, CD70 and CD8 reduces islet inflammation and improves glycaemia in diabetic mice
Authors: Alkhamis T , Barbic J , Crnogorac-Jurcevic T , Greenlaw R E , Peakman M , Jurcevic S 
Published: July 2012

Summary
Destruction of pancreatic islets in type 1 diabetes is caused by infiltrating, primed and activated T cells. In a clinical setting this autoimmune process is already in an advanced stage before intervention therapy can be administered. Therefore, an effective intervention needs to reduce islet inflammation and preserve any remaining islet function. In this study we have investigated the role of targeting activated T cells in reversing autoimmune diabetes. A combination therapy consisting of CD25-, CD70- and CD8-specific monoclonal antibodies was administered to non-obese diabetic (NOD) mice with either new-onset diabetes or with advanced diabetes. In NOD mice with new-onset diabetes antibody combination treatment reversed hyperglycaemia and achieved long-term protection from diabetes (blood glucose &lt;13·9 mmol/l) in &gt;50% of mice. In contrast, in the control, untreated group blood glucose levels continued to increase and none of the mice were protected from diabetes (P &lt; 0·0001). Starting therapy early when hyperglycaemia was relatively mild proved critical, as the mice with advanced diabetes showed less efficient control of blood glucose and shorter life span. Histological analysis (insulitis score) showed islet preservation and reduced immune infiltration in all treated groups, compared to their controls. In conclusion, antibody combination therapy that targets CD25, CD70 and CD8 results in decreased islet infiltration and improved blood glucose levels in NOD mice with established diabetes.
A community of practice view of intervention programmes: the case of women returning to IT
Authors: Panteli Niki 
Published: July 2012

AbstractThe study presents an intervention programme for women returning to the information technology (IT) industry following a career break. This is interpreted through the lens of the community of practice perspective. The longitudinal nature of the case study offered opportunities for in‐depth investigation of participants' experience and development during the process. Using this datum, a mid‐level analytical approach is adopted. It is found that learning about the path to return to IT emerged regardless of the degree of participation in the intervention programme, and this was supported by the diversity and integration embedded in this programme. The implications of the findings for our understanding of intervention programmes are discussed.
Environmental species sorting dominates forest‐bird community assembly across scales
Authors: Özkan Korhan , Svenning Jens‐Christian , Jeppesen Erik 
Published: July 2012

Summary

Environmental species sorting and dispersal are seen as key factors in community assembly, but their relative importance and scale dependence remain uncertain, as the extent to which communities are consistently assembled throughout their biomes.
To address these issues, we analysed bird metacommunity structure in a 1200‐km2 forested landscape (Istranca Forests) in Turkish Thrace at the margin of the Western Palaearctic (WP) temperate‐forest biome. First, we used spatial regressions and Mantel tests to assess the relative importance of environmental and spatial factors as drivers of local species richness and composition within the metacommunity. Second, we analysed species' abundance–occupancy relationship across the metacommunity and used null models to assess whether occupancy is determined by species' environmental niches. Third, we used generalized linear models to test for links between species' metacommunity‐wide occupancy and their broader WP regional populations and assessed whether these links are consistent with environmental species sorting.
There was strong environmental control on local species richness and composition patterns within the metacommunity, but non‐environmental spatial factors had also an important joint role.
Null model analyses on randomized communities showed that species' occupancy across the metacommunity was strongly determined by species' environmental niches, with occupancy being related to niche position marginality.
Species' metacommunity‐wide occupancy correlated with their local abundance as well as with their range size and total abundance for the whole WP, suggesting that the same assembly mechanisms act consistently across local to regional scales. A species specialization index that was estimated by bird species' habitat use across France, incorporating both niche position and breadth, was significantly related to species' occupancy and abundance at both metacommunity and WP regional scales. Hence, the same niche‐related assembly mechanisms appear to act consistently across the WP region.
Overall, our results suggest that the structure of the Istranca Forest' bird metacommunity was predominantly controlled by environmental species sorting in a manner consistent with the broader WP region. However, variability in local community structure was also linked to purely spatial factors, albeit more weakly.
A range‐wide genetic bottleneck overwhelms contemporary landscape factors and local abundance in shaping genetic patterns of an alpine butterfly (Lepidoptera: Pieridae: Colias behrii)
Authors: SCHOVILLE SEAN D. , LAM ATHENA W. , RODERICK GEORGE K. 
Published: July 2012

AbstractSpatial and environmental heterogeneity are major factors in structuring species distributions in alpine landscapes. These landscapes have also been affected by glacial advances and retreats, causing alpine taxa to undergo range shifts and demographic changes. These nonequilibrium population dynamics have the potential to obscure the effects of environmental factors on the distribution of genetic variation. Here, we investigate how demographic change and environmental factors influence genetic variation in the alpine butterfly Colias behrii. Data from 14 microsatellite loci provide evidence of bottlenecks in all population samples. We test several alternative models of demography using approximate Bayesian computation (ABC), with the results favouring a model in which a recent bottleneck precedes rapid population growth. Applying independent calibrations to microsatellite loci and a nuclear gene, we estimate that this bottleneck affected both northern and southern populations 531–281 years ago, coinciding with a period of global cooling. Using regression approaches, we attempt to separate the effects of population structure, geographical distance and landscape on patterns of population genetic differentiation. Only 40% of the variation in FST is explained by these models, with geographical distance and least‐cost distance among meadow patches selected as the best predictors. Various measures of genetic diversity within populations are also decoupled from estimates of local abundance and habitat patch characteristics. Our results demonstrate that demographic change can have a disproportionate influence on genetic diversity in alpine species, contrasting with other studies that suggest landscape features control contemporary demographic processes in high‐elevation environments.
Asymmetric adaptation to indolic and aliphatic glucosinolates in the B and Q sibling species of Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: ELBAZ M. , HALON E. , MALKA O. , MALITSKY S. , BLUM E. , AHARONI A. , MORIN S. 
Published: July 2012

AbstractThe role glucosinolates play in defending plants against phloem feeders such as aphids and whiteflies is currently not clear as these herbivores may avoid bringing glucosinolates from the phloem sap into contact with myrosinase enzymes. Here, we investigated the effects of high levels of aliphatic and indolic glucosinolates on life history traits and detoxification gene expression in two sibling species, B and Q, of the whitefly Bemisia tabaci. High levels of aliphatic glucosinolates decreased the average oviposition rate of both species and reduced the survival and developmental rate of Q nymphs. High levels of indolic glucosinolates decreased the oviposition rate and survival of nymphal stages of the B species and the developmental rate of both species. Molecular analyses revealed two major asymmetries between the B and Q species. First, specific GST genes (BtGST1 and BtGST2) were significantly induced during exposure to indolic glucosinolates only in Q. This may reflect the genes putative involvement in indolic glucosinolates detoxification and explain the species’ good performance on plants accumulating indolic glucosinolates. Second, the constitutive expression of eight of the 10 detoxification genes analysed was higher in the Q species than in the B species. Interestingly, four of these genes were induced in B in response to high levels of glucosinolates. It seems, therefore, that the B and Q species differ in their ‘optimal defence strategy’. B utilizes inducible defences that are profitable if the probability of experiencing the stress is small and its severity is low, while Q invests significant resources in being always ‘ready’ for a challenge.
Triple‐phase abdominal computed tomography for detecting spontaneous portopulmonary shunts in cirrhotic patients
Authors: Gonzalez German , Wilkinson Lana M , Carcano Carolina , Kumar Anand , Mohammed Tan‐Lucien , Lurix Einar , Castro Fernando , Kirsch Jacobo 
Published: July 2012

AbstractBackground and AimData on prevalence of portopulmonary shunts (PPS) are quite limited. Most studies have used cineportography or echocardiography for diagnosis. Only few recent case reports have reported the use of computed tomography (CT) for identification of PPS. This study tried to determine the prevalence of PPS in patients with cirrhosis using contrast‐enhanced CT of the abdomen, and to determine their association with demographic and clinical characteristics.MethodsA total of 150 subjects with cirrhosis who had previously undergone triple‐phase CT were analyzed. PPS was diagnosed when at least one esophageal varix met all of the following criteria: (i) it could be followed cephalad into the chest to the level of the inferior pulmonary vein or left atrium; (ii) it abutted the wall of either of these structures; (iii) it had luminal continuity with one of these structures; and (iv) it was no longer seen one slice above the level of contact.ResultsOf 150 subjects, 18 were excluded for incomplete data. The prevalence of PPS was found to be 26/132 (19.7%). Of these, 14 (53.8%) patients had PPS draining into the left atrium and 12 (46.2%) had those draining into one of the pulmonary veins. Presence of PPS was associated with the presence of varices at endoscopy, ascites, thrombocytopenia and splenomegaly.ConclusionIn our study, the largest study on PPS to date, the prevalence of PPS in cirrhotic patients using triple phase CT was found to be 19.7%. CT may be a useful technique to study PPS and their clinical implications.
Ten‐day sequential versus triple therapy for Helicobacter pylori eradication: A prospective, open‐label, randomized trial
Authors: Chung Jun‐Won , Jung Young Kul , Kim Yoon Jae , Kwon Kwang Ahn , Kim Jung Ho , Lee Jong Joon , Lee Sung Min , Hahm Ki Baik , Lee Sun Mi , Jeong Jin Yong , Yun Sung‐Cheol 
Published: July 2012

AbstractBackground and AimIncreased resistance of Helicobacter pylori to antibiotics has increased the need to develop new first‐line treatments for H. pylori. We have prospectively evaluated 10‐day sequential versus conventional triple therapy in peptic ulcer patients.MethodsOne hundred and fifty‐nine patients with peptic ulcer diseases were prospectively randomized to receive 10 days of lansoprazole, amoxicillin, and clarithromycin (conventional triple therapy) or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Post‐treatment H. pylori status was determined by the 13C‐urea breath test. Eradication rates, antibiotic resistance rates by agar dilution method, drug compliance, and side‐effects were compared.ResultsThe intention‐to‐treat eradication rates were 75.9% (95% CI 66.5–85.3%, 60/79) in the sequential therapy group and 58.7% (95% CI 47.9–69.5%, 47/80) in the conventional triple therapy group (P = 0.01), while the per‐protocol eradication rates were 86.8% (95% CI 78.7–94.8%, 59/68) and 67.6% (95% CI 56.5–78.7%, 46/68) (P = 0.01), respectively. Compliance and side‐effects were similar in the two groups. Culture of H. pylori showed that 18.2% were resistant to clarithromycin, 41.9% to metronidazole. Dual resistance to both antibiotics was 9.6%.ConclusionsAlthough 10‐day sequential therapy yielded a higher H. pylori eradication rate than 10‐day conventional triple therapy, the sequential therapy protocol did not result in a sufficiently satisfactory eradication rate. This might be related to the higher antibiotics resistance rate especially to dual resistance. More effective regimens are needed to overcome antibiotic resistance in Korea.
Real medicine
Authors: Wilson Hayden , Payne Donald 
Published: July 2012

AbstractA substantial part of a paediatrician's work increasingly involves caring for children and young people with mental health, developmental, emotional and behavioural problems. Over time, recognition of these aspects has redefined and broadened the notion of what classically constitutes ‘Paediatrics.’ This paper discusses the ways in which paediatricians and psychiatrists can support each other in this work. It highlights the role of supervision and specifically advocates for the expansion of consultation/liaison psychiatry services.
Teachers’ perceptions, beliefs and concerns about cyberbullying
Authors: Eden Sigal , Heiman Tali , Olenik‐Shemesh Dorit 
Published: July 2012

AbstractSchools and teachers nowadays face new difficulties and challenges as a result of the fast growth of cyberbullying. The aim of the study is to examine the perceptions, beliefs and concerns about cyberbullying, as well as the needs, of a professionally diverse group of teachers. Three‐hundred and twenty‐eight teachers (88.4% female, 11.6% male) from different types of schools and professional foci were randomly selected and completed a cyberbullying questionnaire regarding their perceptions of cyberbullying and about their personal experiences in relation to cyberbullying. They also provided background information. Findings indicate that teachers noted that cyberbullying is a problem in their school, suggesting that urgent attention be paid to three aspects: policy making, enhancing awareness of the school team and coping strategies for parents. About half the teachers reported that students complain of harassment through the mobile phone and Internet, and some teachers were themselves cyberbullied. It was found that the teachers’ gender, education level and the age of the students they taught affected their level of concern about cyberbullying, and therefore how credible they found the school's commitment to act on it. Female teachers expressed more concern than male teachers, as did teachers of younger children. Special education teachers were more concerned than mainstream teachers and were more likely to believe that the cyberbullying must be confronted. The results contribute to our understanding of the teachers’ perceptions, beliefs and concerns about cyberbullying, which could serve as a basis for developing policy guidelines in schools as well as establishing programs for school teachers to cope with cyberbullying.
Success rate, efficacy, and safety/tolerability of overnight switching from immediate‐ to extended‐release pramipexole in advanced Parkinson's disease
Authors: Schapira A. H. V. , Barone P. , Hauser R. A. , Mizuno Y. , Rascol O. , Busse M. , Debieuvre C. , Fraessdorf M. , Poewe W. 
Published: July 2012

Background and purposeFor Parkinson's disease (PD), an extended‐release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate‐release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER.MethodsLevodopa users experiencing motor fluctuations were randomized to adjunctive double‐blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open‐label maintenance dosage.ResultsOne week post‐switch, 86.2% of 123 IR‐to‐ER and 83.8% of 105 ER‐to‐ER patients had ≤15% (or ≤3‐point, for pre‐switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1‐h increase in daily OFF‐time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of −14.8 (1.5) for IR‐to‐ER and −13.3 (1.6) for ER‐to‐ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR‐to‐ER and 4.9% for ER‐to‐ER.ConclusionsBy OFF‐time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.
‘It's Always English in the Cop Shop’: Accounts of Minority Language Use in the Criminal Justice System in Wales
Authors: Madoc‐Jones Iolo , Parry Odette 
Published: July 2012

AbstractEuropean language activists have successfully campaigned for the right to use regional or minority languages in judicial contexts. Despite this, such rights are rarely exercised. This is commonly understood as a function of the unavailability and/or inaccessibility of appropriate language services, so judicial authorities in a range of countries are urged to do more to meet their obligations to meet the needs of minority language speakers. The article draws on a study of language use in one criminal justice system where the right to use a minority language exists. It uses a discourse analytic approach to explore how first‐language Welsh‐speaking criminal justice service users account for their choice, and usage, of language, and what purposes these accounts may serve for narrators. Despite their commitment to the Welsh language, none of the study respondents used Welsh in their most recent episodes in the police station or at court. Two competing discursive constructions were evident in respondent accounts which served specific objectives for narrators. A ‘down to them’ discursive construction, which drew on wider imperialist discourses, positioned narrators as powerless victims of a system in which they had no choice over language. This construction legitimised narrators’ claim to Welshness and castigated agencies of the criminal justice system. Simultaneously, however, narrators deployed ‘up to me’ discursive constructions to demonstrate resistance to the role of victim. This construction positioned narrators as more powerful and as exercising agency and choice in the criminal justice system. The article thus challenges oversimplified understandings of minority language use and non‐use in the criminal justice system.