bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maraviroc:in vitroassessment of drug–drug interaction potential
Authors: Hyland Ruth , Dickins Maurice , Collins Claire , Jones Hannah , Jones Barry 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT• Maraviroc is known to undergo oxidative metabolismin vivoand is a substrate for cytochrome P450 (CYP).• Simcyp™ has recently become more widely used for the prediction of CYP‐mediated drug–drug interactions (DDIs) usingin vitrometabolism data.WHAT THIS STUDY ADDS• Maraviroc has been identified as a CYP3A4 substrate and the kinetic constants characterized.• The predicted DDIs associated with maraviroc as a CYP3A4 substrate using Simcyp™ have been compared against the clinical data.• This study demonstrates the value of a reliable Simcyp™ model for prediction of DDIs.AIMSTo characterize the cytochrome P450 enzyme(s) responsible for the N‐dealkylation of maravirocin vitro, and predict the extent of clinical drug–drug interactions (DDIs).METHODSHuman liver and recombinant CYP microsomes were used to identify the CYP enzyme responsible for maraviroc N‐dealkylation. Studies comprised enzyme kinetics and evaluation of the effects of specific CYP inhibitors.In vitrodata were then used as inputs for simulation of DDIs with ketoconazole, ritonavir, saquinavir and atazanvir, using the Simcyp™ population‐based absorption, distribution, metabolism and elimination (ADME) simulator. Study designs for simulations mirrored those actually used in the clinic.RESULTSMaraviroc was metabolized to its N‐dealkylated product via a single CYP enzyme characterized by aKmof 21 µM andVmaxof 0.45 pmol pmol−1 min−1in human liver microsomes and was inhibited by ketoconazole (CYP3A4 inhibitor). In a panel of recombinant CYP enzymes, CYP3A4 was identified as the major CYP responsible for maraviroc metabolism. Using recombinant CYP3A4, N‐dealkylation was characterized by aKmof 13 µM and aVmaxof 3 pmol pmol−1CYP min−1. Simulations therefore focused on the effect of CYP3A4 inhibitors on maraviroc pharmacokinetics. The simulated median AUC ratios were in good agreement with observed clinical changes (within twofold in all cases), although, in general, there was a trend for overprediction in the magnitude of the DDI.CONCLUSIONMaraviroc is a substrate for CYP3A4, and exposure will therefore be modulated by CYP3A4 inhibitors. Simcyp™ has successfully simulated the extent of clinical interactions with CYP3A4 inhibitors, further validating this software as a good predictor of CYP‐based DDIs.
Efficacy of the Incredible Years Programme as an early intervention for children with conduct problems and ADHD: long‐term follow‐up
Authors: Jones K. , Daley D. , Hutchings J. , Bywater T. , Eames C. 
Published: April 2008

AbstractBackground  This study examined the long‐term efficacy of the Incredible Years (IY) BASIC Parenting Programme delivered as a preventive intervention with parents of pre‐school children who display signs of attention deficit hyperactivity disorder (ADHD) and conduct problems. Families were followed up after the completion of a controlled trial with 11 Sure Start areas in North and Mid‐Wales and North West England.Methods  Participants in the study were 50 pre‐school children whose parents had received the intervention. Child ADHD symptoms were assessed at baseline, at follow‐up one (6 months after baseline); at follow‐up two (12 months after baseline); and at follow‐up three (18 months after baseline). Families in the original waiting‐list control group were not assessed after follow‐up one as they had subsequently received the same intervention.Results  The significant post‐intervention improvements in child ADHD symptoms evident at follow‐up one were maintained over time, as demonstrated by statistical and clinical stability of measures. No significant differences were found for ADHD symptoms across each follow‐up, indicating that the gains made post intervention were maintained for at least 12 months, with 57% of the sample maintaining scores below the clinical cut‐off on the Conners. Eighty‐six, 58, and 30 per cent respectively had maintained at least a modest, large, or very large improvement in ADHD symptoms at follow‐up three.Conclusions  Findings from this study suggest that the IY psychosocial treatment programme is a valuable intervention in the longer term for many pre‐school children displaying early signs of ADHD.
Family‐centred service coordination in childhood health and disability services: the search for meaningful service outcome measures
Authors: Trute B. , Hiebert‐Murphy D. , Wright A. 
Published: April 2008

AbstractBackground  Potential service outcome measures were tested for their utility in the assessment of the quality of ‘family centred’ service coordination in the provincial network of children's disability services in Manitoba, Canada.Methods  This study is based on in‐home survey data provided by 103 mothers at 6 and 18 months following assignment of a ‘dedicated’ service coordinator. Service outcome indicators included measures of parent self‐esteem, parenting stress, family functioning and the need for family support resources.Results  Hierarchical regression analyses showed no relationship between level of quality of family‐centred service coordination and standardized psychosocial measures of parent and family functioning. However, family centredness of service coordination was found to predict significant reduction in level of family need for psychosocial support resources after 18 months of contact with a service coordinator.Conclusions  Outcome measures that are focused on specific and tangible results of service coordination appear to be of higher utility in service quality assessment than are more global, standardized measures of parent and family functioning.
Included but isolated: early intervention programmes provision for children and families with chronic respiratory support needs
Authors: Graham R. J. , Pemstein D. M. , Palfrey J. S. 
Published: April 2008

AbstractPurpose  To measure enrolment of children with mechanical respiratory support needs within the Massachusetts early intervention programmes (EIP) and describe challenges in execution of individual family service plans (IFSPs).Methods  Mixed methods provided a complementary assessment. Quantitative data were collected in 2005 from the Commonwealth of Massachusetts EIP administrative database as part of a cross‐sectional state census. Qualitative data were retrieved from EIP regional coordinators in a key informant focus group. Descriptive statistics were used for quantitative survey data. Audio‐recordings were transcribed verbatim and a qualitative, thematic analysis was undertaken.Results  Four hundred and eighty children requiring mechanical respiratory support at the time of EIP enrolment were identified between 1 July 1997 and 1 January 2005. Focus group analysis revealed themes including: (1) barriers to community transition; (2) community expertise and training; (3) interface with medical providers; and (4) the role of web‐based resources. Isolation of families emerged as a recurrent and resounding concept, relating to all of the themes.Conclusions  Findings support the assumption that implementation of IFSPs for the cohort of children with chronic mechanical respiratory support needs in EIPs is challenging. Barriers reflect inconsistent care coordination and practical encumbrances, contributing to the physical and social isolation of these children and their families.
Health behaviours, risk‐taking and conceptual changes among schoolchildren aged 7 to 19 years in semi‐rural Sweden
Authors: Olsson A. , Fahlén I. , Janson S. 
Published: April 2008

AbstractBackground  This study covers a broad age group (7–19 years) and includes a wide range of themes. The aim is to describe how various behaviours, complaints and conceptual changes come into play and to discuss the factors that might support or hamper the happiness and well‐being of growing children and adolescents. We also discuss the implications of our findings for future prevention programmes.Methods  This cross‐sectional study included all schoolchildren in a semi‐rural district in Sweden (2181 pupils). A structured classroom questionnaire was used but the children were also given the opportunity to describe in their own words what was important for their happiness and well‐being.Results  Mean response rate was 85%. Most changes in behaviour occurred between 11 and 14 years of age. Girls had a more rapid process of change than boys. Both girls and boys experienced stress in their relations with peers, parents and teachers. Gender differences in emotional support were prominent. Regardless of age and sex, all schoolchildren asked for a richer choice of leisure time activities, a place where they could meet with friends and caring teachers, parents and adults in the surrounding community.Conclusions  Adolescence was perceived as a risky and problematic period not only by adults but also by the adolescents themselves. However, the perceived risks and the worries differed. While the adults mainly worried about the early onset of smoking and drug use, the schoolchildren worried about their social situation and their personal relationships. After decades of preventive programmes in Swedish schools, only modest results are seen. To be effective, future preventive programmes probably have to focus more on the conceptual world of the growing child.
How neighbourhoods influence child maltreatment: a review of the literature and alternative pathways
Authors: Reading Richard 
Published: April 2008

.

Coulton C.J.,
Crampton D.S.,
Irwin M.,
Spilsbury J.C. &
Korbin J.E.
(
2007
)

,
31
,
1117
–
1142
.

DOI: 10.1016/j.chiabu.2007.03.023.
Objective  To review the literature on the relationships between neighbourhoods and child maltreatment, and identify future directions for research in this area.Method  A search of electronic databases and a survey of experts yielded a list of 25 studies on the influence of geographically defined neighbourhoods on child maltreatment. These studies were then critically reviewed by an interdisciplinary research team.Results  Numerous studies demonstrate that child maltreatment cases are concentrated in disadvantaged areas. A number of socio‐economic characteristics of neighbourhoods have been shown to correlate with child maltreatment rates as measured by official reports to child protective service agencies. Only a few studies examine direct measures of parenting behaviours associated with maltreatment, and these show a weaker relationship with neighbourhood disadvantage. Moreover, the processes that link neighbourhood conditions to either maltreatment reports or parenting behaviours are not yet confirmed by the research literature. Selection bias, neighbourhood definitions and spatial influences are largely uncontrolled in the existing research.Conclusions  We propose a framework for pursuing further study of neighbourhoods and child maltreatment that addresses the gaps in the current literature. Neighbourhood‐based strategies to prevent and reduce child maltreatment will be enhanced by research that provides a better understanding of how neighbourhood conditions act as stressors or supports for families at risk of child maltreatment.
A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open‐label parallel study
Authors: Sathyapalan Thozhukat , Cho Li Wei , Kilpatrick Eric S. , Coady Anne‐Marie , Atkin Stephen L. 
Published: April 2008

SummaryContext  Weight loss and metformin therapy are reported to be beneficial in improving the biochemical hyperandrogenaemia and insulin resistance of polycystic ovary syndrome (PCOS). Rimonabant has been found to reduce weight and improve the metabolic profile in patients with obesity, type 2 diabetes and metabolic syndrome.Objective  To compare the effects of insulin sensitization with metformin to weight reduction by rimonabant on biochemical hyperandrogenaemia and insulin resistance in patients with PCOS.Design  A randomized, open‐label parallel study.Setting  Endocrinology outpatient clinic in a referral centre.Subjects  Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index (BMI) ≥ 30 kg/m2 were recruited.Intervention  Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant.Main outcome measures  The primary end‐point of the study was a change in total testosterone.Results  After 12 weeks of rimonabant there was a significant reduction (mean ± SEM) in weight (104·6 ± 4·6 vs. 98·4 ± 4·7 kg, P < 0·01), waist circumference (116·0 ± 3·3 vs. 109·2 ± 3·7 cm, P < 0·01), hip circumference (128·5 ± 4·0 vs. 124·1 ± 4·2 cm, P < 0·03), waist–hip ratio (0·90 ± 0·02 vs. 0·88 ± 0·01, P < 0·01) free androgen index (FAI) (26·6 ± 6·1 vs. 16·6 ± 4·1, P < 0·01), testosterone [4·6 ± 0·4 vs. 3·1 ± 0·3 nmol/l (132·7 ± 11·5 vs. 89·4 ± 8·65 ng/dl), P < 0·01] and insulin resistance as measured by the homeostasis model assessment (HOMA) method (4·4 ± 0·5 vs. 3·4 ± 0·4, P = 0·05). There was no change in any of these parameters in the metformin‐treated group.Conclusion  This study suggests that the weight loss through rimonabant therapy may be of use in patients with PCOS and appears superior to insulin sensitization by metformin in reducing the FAI and insulin resistance in obese PCOS patients treated over a 12‐week period.
Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas
Authors: Georgitsi Marianthi , De Menis Ernesto , Cannavò Salvatore , Mäkinen Markus J. , Tuppurainen Karoliina , Pauletto Paolo , Curtò Lorenzo , Weil Robert J. , Paschke Ralf , Zielinski Grzegorz , Wasik Anna , Lubinski Jan , Vahteristo Pia , Karhu Auli , Aaltonen Lauri A. 
Published: April 2008

SummaryObjective  Pituitary adenomas occur rarely in childhood and adolescence. Pituitary adenoma predisposition (PAP) has been recently associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The aim of the study was to examine the proportion of germline AIP mutations in apparently sporadic paediatric pituitary adenomas.Design  Genomic DNA was analysed for mutations in the AIP gene, by PCR amplification and direct sequencing.Patients  A population‐based cohort consisting of 36 apparently sporadic paediatric pituitary adenoma patients, referred to two medical centres in Italy, was included in the study. Patients were either less than 18 years at diagnosis, or showed clinical evidence of adenoma development before the age of 18 years.Results  A heterozygous in‐frame deletion Y248del (c.742_744delTAC) was identified in one GH‐secreting adenoma patient. Loss of heterozygosity (LOH) analysis of tumour DNA revealed the loss of the wild‐type allele. First degree relatives carrying the mutation were clinically unaffected.Conclusions  While mutations were absent in non‐GH‐secreting adenoma patients, germline AIP mutations can be found in children and adolescents with GH‐secreting tumours, even in the absence of family history. The present study reports the AIP mutation analysis results on patients of a single ethnic origin. Clearly, further studies are needed to improve our knowledge on the role of AIP in paediatric pituitary adenomas.
Primary aldosteronism (PA) and endothelial progenitor cell (EPC) bioavailability
Authors: Verhovez Andrea , Zeoli Annarita , Williams Tracy Ann , Morello Fulvio , Brizzi Maria Felice , Veglio Franco , Mulatero Paolo 
Published: April 2008

SummaryObjective  Patients with primary aldosteronism (PA) experience more cardiovascular events than patients with essential hypertension matched for risk factor profile. Endothelial progenitor cells (EPC) represent a bone marrow‐derived cell population implicated in vascular healing whose number correlates to the cardiovascular risk factor profile. Aldosterone has been reported to decrease EPC proliferation in rats.Design and patients  We assessed (i) the growth characteristics of EPC from six PA patients and six matched normotensive controls; (ii) the growth characteristics of EPC treated with increasing doses of aldosterone.Measurements  Senescence and cell‐cycle analysis of EPC from PA patients and normotensive controls and of aldosterone‐treated EPC from healthy volunteers.Results  No difference was found in the senescence rate between EPC from PA patients (72·4% senescent cells) and controls (70·7%, P > 0·05). No difference was also found in the cell‐cycle distribution determined by FACS (controls: 75·2% cells in G0/G1 phase; PA: 73·5%, P > 0·05). Incubation of EPC with aldosterone did not modify their senescence rate (controls: 72·4% senescent cells; aldosterone 10 nmol/l: 70·9%; aldosterone 100 nmol/l 71·6%, P > 0·05 for all comparisons) and cell‐cycle distribution (controls: 73·3% cells in G0/G1 phase; aldosterone 10 nmol/l: 74·9%; aldosterone 100 nmol/l: 75·4%, P > 0·05 for all comparisons). No expression of the mineralocorticoid receptor (MR) transcript was found in EPC by RT‐PCR analysis.Conclusions  High aldosterone levels, both in PA patients and in vitro, exert no direct or indirect effect on EPC growth characteristics.
Amino acid sources in the adult diet do not affect life span and fecundity in the fruit‐feeding butterfly Bicyclus anynana
Authors: MOLLEMAN FREERK , DING JIMIN , WANG JANE‐LING , BRAKEFIELD PAUL M , CAREY JAMES R , ZWAAN BAS J 
Published: April 2008

Abstract 1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit‐feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit‐feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice‐amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.
Integrating ecology with biogeography using landscape characteristics: a case study of subtidal habitat across continental Australia
Authors: Connell Sean D. , Irving Andrew D. 
Published: April 2008

AbstractAim  We aimed to redress a current limitation of local ecological studies (i.e. piecemeal information on specific taxa) by integrating existing ecological knowledge with quantifiable patterns in primary habitat (i.e. composition, distribution and cover) from local to continental scales. By achieving this aim, we sought to provide a biogeographical framework for the interpretation of variation in the ecology of, and threats to, subtidal rocky landscapes.Location  The subtidal rocky coast of continental Australia, with longitudinal comparisons spanning > 4000 km of southern coast (115°03′ E–153°60′ E) between latitudes of 33°05′ S and 35°36′ S, and latitudinal comparisons across 26°40′ S to 37°08′ S of eastern Australia.Methods  The frequency and size of patches of major benthic habitat were quantified to indicate contemporary function (ecology) and to establish patterns that may result from contrasting regional‐scale processes (biogeography). This was achieved by quantifying the composition and patchiness of key subtidal habitats across the continent and relating them to the known ecology of subsets of locations in each region. A nested design of several spatial scales (1000s, 100s, 10–1 km) was adopted to distinguish patterns at local through to biogeographical scales.Results  We show biogeography (in terms of longitude and latitude) to have a fundamental influence on the patterns of abundance and composition of subtidal habitats across regional (1000s of kilometres) to local (10s of kilometres to metres) scales. Across the continent, the most fundamental patterns related to (1) the proportion of rock covered by kelp forests, as related to particular functional groups of herbivores, and (2) the small‐scale heterogeneity (metres) that characterizes these forests.Main conclusions  We interpret these results within a framework of alternative processes known to maintain habitat heterogeneity across these regions (e.g. productivity versus consumption as shapers of habitat structure). These interpretations illustrate how regional differences in ecological patterns and processes can create contradictory outcomes for the management of natural resources. We suggest that researchers and managers of natural resources alike may benefit from understanding local issues (e.g. the effects of fishing and its synergies with water pollution) in their biogeographical contexts.
Biogeographical revision of Argentina (Andean and Neotropical Regions): an analysis using freshwater fishes
Authors: López Hugo L. , Menni Roberto C. , Donato Mariano , Miquelarena Amalia M. 
Published: April 2008

AbstractAim To provide an objective geographic framework displaying the distribution patterns of freshwater fishes from Argentina.Location Argentina, southern South America.Methods Parsimony analysis of endemicity (PAE) and similarity and cluster analyses were applied to presence and absence data on 440 fish species from 52 localities in Argentina. Both 50% majority consensus and strict consensus analyses were undertaken in the first case, and the Jaccard similarity index was used in the second.Results Five ichthyogeographic provinces are described based on a PAE of the 52 localities. A cluster analysis provided similar results.Main conclusions The following zoogeographic provinces are proposed for Argentine freshwater fish fauna following the International Code of Area Nomenclature: Andean Cuyan, Patagonian, Aymaran, Great Rivers and Pampean. The former two are placed within the Andean Subregion of the Austral Region, and the latter three within the Neotropical Subregion of the Holotropical Region. These provinces, based on results coinciding with PAE and cluster analysis, represent the first classification of Argentine provinces based on objective methods. Some small regions of endemism and some localities remain separated from the proposed regions. The new scheme includes valuable empirical information from previous schemes, and is in agreement with ecological zones and other environmental arrangements proposed earlier.