bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics of atazanavir/ritonavir in HIV‐1‐infected children and adolescents
Authors: Foissac Frantz , Blanche Stéphane , Dollfus Catherine , Hirt Déborah , Firtion Ghislaine , Laurent Corinne , Treluyer Jean‐Marc , Urien Saïk 
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Population pharmacokinetics has been studied in adult patients. Tenofovir disoproxil fumarate (TDF) co‐medication could decrease atazanavir/ritonavir (ATV/r) exposure.WHAT THIS STUDY ADDS• This first ATV/r population analysis in children and adolescents provides useful insights into the fate of this drug and shows that the allometric scaling of clearance and volume parameters based on bodyweight reduced the associated between‐subject variability. Moreover, the effects of combined ritonavir and tenofovir on ATV clearance are precisely quantified.AIMS To investigate atazanavir (ATV) population pharmacokinetics in children and adolescents, establish factors that influence ATV pharmacokinetics and investigate the ATV exposure after recommended doses.METHODS Atazanavir concentrations were measured in 51 children/adolescents during a mean therapeutic monitoring follow up of 6.6 months. A total of 151 ATV plasma concentrations were obtained, and a population pharmacokinetic model was developed with NONMEM. Patients received ATV alone or boosted with ritonavir.RESULTS Atazanavir pharmacokinetics was best described by a one‐compartment model with first‐order absorption and elimination. The effect of bodyweight was added on both apparent elimination clearance (CL/F) and volume of distribution using allometric scaling. Atazanavir CL/F was reduced by ritonavir by 45%. Tenofovir disoproxil fumarate (TDF) co‐medication (300 mg) increased significantly by 25% the atazanavir/ritonavir (ATV/r) CL/F. Mean ATV/r CL/F values with or without TDF were 8.9 and 7.1 L h−1 (70 kg)−1, respectively. With the recommended 250/100 mg and 300/100 mg ATV/r doses, the exposure was higher than the mean adult steady‐state exposure in the bodyweight range of 32–50 kg.CONCLUSIONS To target the mean adult exposure, children should receive the following once‐daily ATV/r dose: 200/100 mg from 25 to 39 kg, 250/100 mg from 39 to 50 kg and 300/100 mg above 50 kg. When 300 mg TDF is co‐administered, children should receive (ATV/r) at 250/100 mg between 35 and 39 kg, then 300/100 mg over 39 kg.
Mechanisms of Phragmites australis invasion: feedbacks among genetic diversity, nutrients, and sexual reproduction
Authors: Kettenring Karin M. , McCormick Melissa K. , Baron Heather M. , Whigham Dennis F. 
Published: June 2011

Summary1. A fundamental challenge to invasion ecology is to determine what factors cause an exotic species to spread rapidly long after the initial introduction. The increase of a resource (e.g. nitrogen) could trigger an expansion, but in other instances, species have overcome biological limitations (e.g. an Allee effect) like accumulating sufficient genetic diversity for successful reproduction. Understanding the ecological mechanisms governing plant invasions, such as nutrient enrichment or Allee effects, can be used to improve invasive plant management.2. We used the invasive, introduced grass Phragmites australis as a model to evaluate the role of nutrient enrichment and Allee effects in invasion. Based on recent studies that demonstrated the importance of sexual reproduction in this plant’s spread, we chose to focus our efforts on reproductive output. We examined the effects of patch‐level genetic diversity on viable seed production across watersheds of the Chesapeake Bay, USA, with differing levels of anthropogenic development (a proxy for nutrient enrichment). In an outdoor mesocosm experiment, we treated Phragmites plants originating from forested and developed watersheds with elevated vs. ambient nutrients and cross vs. self‐pollination and determined the effects on viable seed, floret and inflorescence production.3. The proportion of viable seeds produced at field sites varied widely and was not directly related to watershed development. Instead, seed viability was positively related to patch‐level genetic diversity, and patches in more developed watersheds had higher genetic diversity. Also, plants in larger patches produced a higher proportion of viable seeds. In the mesocosm experiment, seed viability was substantially higher for out‐crossed plants. Elevated nutrients resulted in greater floret and inflorescence production, particularly for plants originating from developed vs. forested watersheds.4. These findings have important management implications: small populations should be controlled before they accumulate sufficient genetic variation for prolific viable seed production, and landscape‐scale nutrient management could further limit reproductive output.5. Synthesis and applications. Our research shows how nutrient enrichment and a weak Allee effect can interact across multiple scales to impact invasion success and how understanding the ecological mechanisms governing plant invasions can be used to better inform invasive plant management.
Proton‐driven sucrose symport and antiport are provided by the vacuolar transporters SUC4 and TMT1/2
Authors: Schulz Alexander , Beyhl Diana , Marten Irene , Wormit Alexandra , Neuhaus Ekkehard , Poschet Gernot , Büttner Michael , Schneider Sabine , Sauer Norbert , Hedrich Rainer 
Published: June 2011

SummaryThe vacuolar membrane is involved in solute uptake into and release from the vacuole, which is the largest plant organelle. In addition to inorganic ions and metabolites, large quantities of protons and sugars are shuttled across this membrane. Current models suggest that the proton gradient across the membrane drives the accumulation and/or release of sugars. Recent studies have associated AtSUC4 with the vacuolar membrane. Some members of the SUC family are plasma membrane proton/sucrose symporters. In addition, the sugar transporters TMT1 and TMT2, which are localized to the vacuolar membrane, have been suggested to function in proton‐driven glucose antiport. Here we used the patch‐clamp technique to monitor carrier‐mediated sucrose transport by AtSUC4 and AtTMTs in intact Arabidopsis thaliana mesophyll vacuoles. In the whole‐vacuole configuration with wild‐type material, cytosolic sucrose‐induced proton currents were associated with a proton/sucrose antiport mechanism. To identify the related transporter on one hand, and to enable the recording of symporter‐mediated currents on the other hand, we electrophysiologically characterized vacuolar proteins recognized by Arabidopsis mutants of partially impaired sugar compartmentation. To our surprise, the intrinsic sucrose/proton antiporter activity was greatly reduced when vacuoles were isolated from plants lacking the monosaccharide transporter AtTMT1/TMT2. Transient expression of AtSUC4 in this mutant background resulted in proton/sucrose symport activity. From these studies, we conclude that, in the natural environment within the Arabidopsis cell, AtSUC4 most likely catalyses proton‐coupled sucrose export from the vacuole. However, TMT1/2 probably represents a proton‐coupled antiporter capable of high‐capacity loading of glucose and sucrose into the vacuole.
Validation study of the Leeds Dyspepsia Questionnaire in a multi‐ethnic Asian population
Authors: Mahadeva Sanjiv , Chan Wah‐Kheong , Mohazmi Mohammed , Sujarita Ramanujam , Goh Khean‐Lee 
Published: June 2011

AbstractBackground and Aim:  Outcome measures for clinical trials in dyspepsia require an assessment of symptom response. There is a lack of validated instruments assessing dyspepsia symptoms in the Asian region. We aimed to translate and validate the Leeds Dyspepsia Questionnaire (LDQ) in a multi‐ethnic Asian population.Methods:  A Malay and culturally adapted English version of the LDQ were developed according to established protocols. Psychometric evaluation was performed by assessing the validity, internal consistency, test‐retest reliability and responsiveness of the instruments in both primary and secondary care patients.Results:  Between April and September 2010, both Malay (n = 166) and Malaysian English (n = 154) versions were assessed in primary and secondary care patients. Both language versions were found to be reliable (internal consistency was 0.80 and 0.74 (Cronbach's α) for Malay and English, respectively; spearman's correlation coefficient for test‐retest reliability was 0.98 for both versions), valid (area under receiver operating curve for accuracy of diagnosing dyspepsia was 0.71 and 0.77 for Malay and English versions, respectively), discriminative (median LDQ score discriminated between primary and secondary care patients in Malay (11.0 vs 20.0, P < 0.0001) and English (10.0 vs 14.0, P = 0.001), and responsive (median LDQ score reduced after treatment in Malay (17.0 to 14.0, P = 0.08) and English (18.0 to 11.0, P = 0.008) to dyspepsia.Conclusions:  The Malaysian versions of the LDQ are valid, reliable and responsive instruments for assessing symptoms in a multi‐ethnic Asian population with dyspepsia.
Effect of warfarin on menstruation and menstrual management of the adolescent on warfarin
Authors: Peake Lyndal J , Grover Sonia R , Monagle Paul T , Kennedy Andrew D 
Published: June 2011

Aim:  The aim of this study was to review a consecutive cohort of adolescent females on warfarin to determine the effect of warfarin on menstruation, management options and their perceived efficacy.Methods:  All female patients on warfarin, over the age of 10 years, as of 31 August 2006, were identified using the Department of Haematology (Royal Children's Hospital) warfarin database. The presence of menorrhagia was defined by clinical indicators.Results:  Of 81 adolescent females on warfarin, 24 (30%) were referred to gynaecology due to a concern about heavy periods and one for anticipatory guidance, on the basis of impending menarche. In 18 cases (22% of the cohort), menorrhagia could be substantiated on the basis of clinical indicators. Nineteen patients required treatment for menorrhagia with the options for treatment being the combined oral contraceptive pill, subdermal hormone administrations, tranexamic acid and the progesterone‐only contraceptive pill. Significant adolescent psychosocial stresses were identified in those adolescents taking warfarin.Conclusions:  Adolescent females on warfarin commonly suffer from menorrhagia. Adolescent review of all teenage girls receiving warfarin therapy is indicated.
Effects of Nordic walking on health‐related quality of life in overweight individuals with Type 2 diabetes mellitus, impaired or normal glucose tolerance
Authors: Fritz T. , Caidahl K. , Osler M. , Östenson C. G. , Zierath J. R. , Wändell P. 
Published: June 2011

Diabet. Med. 28, 1362–1372 (2011)AbstractAims  To assess the effects of 4 months of increased physical activity on health‐related quality of life in overweight individuals with Type 2 diabetes mellitus, normal or impaired glucose tolerance.Methods  We included 212 individuals without severe physical or cardiovascular impairments aged 61 (57–64) years, with BMI of 29 (27.5–32) kg/m2. Numbers are median (25th–75th percentile). Subjects were stratified based on normal glucose tolerance (n = 128), impaired glucose tolerance (n = 34) or Type 2 diabetes mellitus (n = 50). They were randomized into either a control group (n = 125), who maintained unaltered habitual lifestyle, or an exercise intervention group (n = 87), who were directed to engage in Nordic walking with walking poles, 5 h per week over 4 months. Self‐reported physical activity and health‐related quality of life was assessed at the time of inclusion and after 4 months.Results  Baseline health‐related quality of life of this study cohort was similar to, or better than, an age‐ and sex‐matched Swedish population sample, for 12 of 13 scales. Quality of sleep and BMI were improved for participants with normal glucose tolerance after 4 months of Nordic walking, with little or no musculoskeletal pain as compared with control subjects. No correlation was evident between improved quality of sleep and improved BMI.Conclusions  Quality of sleep improved in the group with normal glucose tolerance following 4 months of Nordic walking. BMI reduction did not account for this improvement. Nordic walking can be introduced in a primary health care setting as a low‐cost mode of exercise that promotes weight loss and improved health satisfaction.
Fit for Work? The Influence of Sick Pay and Job Flexibility on Sickness Absence and Implications for Presenteeism
Authors: Irvine Annie 
Published: June 2011

AbstractRecent developments in UK policy on health and employment have sought to change perceptions about what constitutes ‘fitness for work’. With the aim of reducing the incidence and duration of sickness absence, a range of initiatives, including the introduction of the ‘fit note’, are challenging the belief that it is necessary to be 100 per cent well in order to be at work. However, this article suggests that contextual factors independent of health may also influence people's decisions about whether or not to attend work at times of reduced wellness. Drawing upon data from a qualitative study of mental health and employment, this article illustrates how the terms and conditions of a person's employment may influence sickness absence decisions in a number of ways. It is argued that sick pay provisions, size of employer and nature of work may influence both decisions to take time off and decisions about when to return to work. The degree of flexibility to manage one's workload around times of poorer health may also have a bearing on whether people feel able to carry on with their work without recourse to sickness absence. Therefore, it may be important for policy interventions to consider not only health circumstances but also structural/contextual influences on conceptualizations of being ‘fit for work’. The implications of such contextually‐influenced decision‐making for ‘presenteeism’ are also considered. It is suggested that current conceptualizations of presenteeism are somewhat ambiguous; employees coming to work despite ill health is simultaneously presented as a problem and an aspiration.
AFRICAN TOURISM GEOGRAPHIES: EXISTING PATHS AND NEW DIRECTIONS
Authors: ROGERSON CHRISTIAN M. , VISSER GUSTAV 
Published: June 2011

ABSTRACTIn the global profile of scholarship on tourism geographies, Africa is the least represented continent. With Africa's incorporation into the global tourism economy, considerable optimism has been raised by many national governments as well as external international development agencies as to the potential contribution of tourism for social and economic development across the continent. The number of geographical voices interrogating the nexus of tourism and development is small but expanding. This paper provides a review of the existing paths and new directions of tourism geographies of the region of Southern Africa as the context for this special dossier. It is argued that tourism research and debates in Southern Africa are growing in importance, including an expansion of geographical research.
GOVERNANCE STRUCTURES AND THE DISTRIBUTION OF TOURISM INCOME IN NAMIBIAN COMMUNAL LANDS: A NEW INSTITUTIONAL FRAMEWORK
Authors: LAPEYRE RENAUD 
Published: June 2011

ABSTRACTThis paper applies a new institutional framework to analyse the generation and distribution of tourism income in Namibian communal lands. Utilising two of Williamson's four levels of institutions, it is shown that reallocating and securing property rights (rules of the game), is essential to allow rural communities to benefit from tourism activities on their land. Contingent to those rights and local communities' capacity and social capital, a typology of institutional arrangements (play of the game), is proposed that govern relationships between actors (local communities, the private sector and the State), in the tourism sector. Overall, this framework facilitates understanding of why and how actors craft specific governance structures in order to operate tourism activities, redistribute revenues and minimise transaction costs.
PLACE MARKETING IN SHRINKING EUROPE: SOME GEOGRAPHICAL NOTES
Authors: HOSPERS GERT‐JAN 
Published: June 2011

ABSTRACTOne third of Europe's regions is confronted with a shrinking population: they are losing inhabitants due to ageing, low fertility and brain drain. To turn the tide, many local authorities invest in place marketing aimed at attracting new residents and firms. This paper deals with the question as to how useful place marketing to beat demographic shrinkage really is. Theoretical and empirical insights from geography (e.g. place fuzziness, sense of place and locational inertia), are used to argue that there are limits to place marketing to attract newcomers. To illustrate this argument, some examples and data from European territories are presented. We conclude that it is more useful for Europe's shrinking territories to focus on ‘warm’ marketing that tries to retain rather than to attract place customers.
The pharmacology of Adrenomedullin 2/Intermedin
Authors: Hong Yanguo , Hay Debbie L , Quirion Remi , Poyner David R 
Published: June 2011

Adrenomedullin 2 (AM2) or intermedin is a member of the calcitonin gene‐related peptide (CGRP)/calcitonin family of peptides and was discovered in 2004. Unlike other members of this family, no unique receptor has yet been identified for it. It is extensively distributed throughout the body. It causes hypotension when given peripherally, but when given into the CNS, it increases blood pressure and causes sympathetic activation. It also increases prolactin release, is anti‐diuretic and natriuretic and reduces food intake. Whilst its effects resemble those of AM, it is frequently more potent. Some characterization of AM2 has been done on molecularly defined receptors; the existing data suggest that it preferentially activates the AM2 receptor formed from calcitonin receptor‐like receptor and receptor activity modifying protein 3. On this complex, its potency is generally equivalent to that of AM. There is no known receptor‐activity where it is more potent than AM. In tissues and in animals it is frequently antagonised by CGRP and AM antagonists; however, situations exist in which an AM2 response is maintained even in the presence of supramaximal concentrations of these antagonists. Thus, there is a partial mismatch between the pharmacology seen in tissues and that on cloned receptors. The only AM2 antagonists are peptide fragments, and these have limited selectivity. It remains unclear as to whether novel AM2 receptors exist or whether the mismatch in pharmacology can be explained by factors such as metabolism.LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein‐Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐1
A Src family kinase inhibitor improves survival in experimental acute liver failure associated with elevated cerebral and circulating vascular endothelial growth factor levels
Authors: Aspinall Richard J. , Weis Sara M. , Barnes Leo , Lutu‐Fuga Kimberly , Bylund David J. , Pockros Paul J. , Cheresh David A. 
Published: June 2011

AbstractBackground and aims: Acute liver failure (ALF) is frequently complicated by cerebral oedema, systemic inflammation and multiorgan dysfunction. Vascular endothelial growth factor (VEGF) may stimulate liver regeneration but it can also be pro‐inflammatory, activating endothelial cells and increasing permeability, actions mediated through Src kinase signalling. We therefore examined whether a Src inhibitor could have therapeutic potential in ALF.Methods: Murine ALF was induced with azoxymethane. Liver pathology was graded by a blinded examiner and apoptosis quantified by immunohistochemistry. Cerebral VEGF expression was imaged using VEGF‐green fluorescent protein transgenic mice. Circulating and macrophage‐secreted VEGF levels were measured. Experimental animals received a Src inhibitor or vehicle controls.Results: VEGF was undetectable in normal plasma but reached a mean of 835 pg/ml at grade III encephalopathy (P<0.001). Ammonia, lipopolysaccharide and interferon‐gamma acted synergistically to enhance VEGF secretion by macrophages. Production of VEGF by cerebral cortical astrocytes increased with disease progression. Late treatment with inhibitors of Src or VEGF did not improve liver histology, encephalopathy or survival. However, early use of a Src kinase inhibitor significantly reduced hepatic injury, delayed encephalopathy and allowed 25% of mice to survive an otherwise lethal insult.Conclusion: Systemic and cerebral VEGF levels are significantly elevated during experimental ALF and may be exacerbated by hyperammonemia and macrophage activation. Early use of a Src inhibitor reduced hepatocellular injury and enabled survival, indicating such agents may have some promise in the treatment of ALF.
Platelet transfusions in neonates: practices in the United States vary significantly from those in Austria, Germany, and Switzerland
Authors: Cremer Malte , Sola‐Visner Martha , Roll Stephanie , Josephson Cassandra D. , Yilmaz Zeynep , Bührer Christoph , Dame Christof 
Published: June 2011

BACKGROUND: Thrombocytopenia affects 20% to 35% of patients admitted to neonatal intensive care units (NICUs). Platelet (PLT) transfusions are usually administered to neonates with thrombocytopenia at higher thresholds than those used for older children or adults, although there is a paucity of evidence to guide these decisions.STUDY DESIGN AND METHODS: In this study, we used a Web‐based survey to investigate the PLT transfusion thresholds used in Level 1 NICUs (equivalent to Level 3 in the US) in three European countries (Austria, Germany, and Switzerland [AUT/GER/SUI]). This survey was identical to the one that was previously sent to US neonatologists, thus allowing for a direct comparison of their responses to 11 case‐based scenarios.RESULTS: In nine of the scenarios, AUT/GER/SUI neonatologists selected substantially lower PLT transfusion thresholds than US neonatologists (p < 0.0001). Transfusion thresholds were more similar when treating neonatal alloimmune thrombocytopenia and before invasive procedures. The clinical impact of these differences was estimated by extrapolating the AUT/GER/SUI versus the US answers to a cohort of neonates with a birth weight below 1000 g. This suggested that, in AUT/GER/SUI, these neonates would receive 167 PLT transfusions per 1000 infants, compared to 299 PLT transfusions in the United States.CONCLUSION: This first international comparative survey on PLT transfusion practice in neonates reveals substantially higher transfusion thresholds in the United States than in AUT/GER/SUI. Well‐designed clinical studies are needed to address the risks and/or benefits of these different approaches.