bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomy at the end of life: life-prolonging treatment in nursing homes—relatives’ role in the decision-making process
Authors: Dreyer A , Forde R , Nortvedt P 
Published: October 2009

Background:The increasing number of elderly people in nursing homes with failing competence to give consent represents a great challenge to healthcare staff’s protection of patient autonomy in the issues of life-prolonging treatment, hydration, nutrition and hospitalisation. The lack of national guidelines and internal routines can threaten the protection of patient autonomy.Objectives:To place focus on protecting patient autonomy in the decision-making process by studying how relatives experience their role as substitute decision-makers.Design:A qualitative descriptive design with analysis of the contents of transcribed in-depth interviews with relatives.Participants:Fifteen relatives of 20 patients in 10 nursing homes in Norway.Results and Interpretations:The main findings reveal deficient procedures for including relatives in decision-making processes. Relatives have poor knowledge about the end of life, and there is little discussion about their role as substitute decision-makers for patients who are not competent to give consent. Few relatives understand the concept of patient autonomy. In Norway the treating physician is responsible for patient treatment. When relatives are included in discussions on treatment, they perceive themselves as responsible for the decision, which is a burden for them afterwards. This qualitative study describes relatives’ experiences, thus providing important information on the improvement potential with the main objective of safeguarding patient autonomy and caring for relatives.Conclusion:The study reveals failing procedures and thus a great potential for improvement. Both ethical and legal aspects must be addressed when considering patient autonomy.
GENERALIZED LATENT CLASS ANALYSIS BASED ON MODEL DOMINANCE THEORY
Authors: CHEN YIXIN , HUA DONG , LIU FANG 
Published: October 2009

Latent class analysis is a popular statistical learning approach. A major challenge for learning generalized latent class is the complexity in searching the huge space of models and parameters. The computational cost is higher when the model topology is more flexible. In this paper, we propose the notion of dominance which can lead to strong pruning of the search space and significant reduction of learning complexity, and apply this notion to the Generalized Latent Class (GLC) models, a class of Bayesian networks for clustering categorical data. GLC models can address the local dependence problem in latent class analysis by assuming a very general graph structure. However, The flexible topology of GLC leads to large increase of the learning complexity. We first propose the concept of dominance and related theoretical results which is general for all Bayesian networks. Based on dominance, we propose an efficient learning algorithm for GLC. A core technique to prune dominated models is regularization, which can eliminate dominated models, leading to significant pruning of the search space. Significant improvements on the model.
Follow-Up Study of Female Delinquent Adolescents in a Detention Centre: Effectiveness of Psychiatric Intervention as a Mental Health Service
Authors: Ariga Michio , Uehara Toru , Takeuchi Kazuo , Ishige Yoko , Nakano Reiko , Mikuni Masahiko 
Published: October 2009

Background: Results of previous studies suggest that many female offenders have co-morbid psychiatric disorders, which require mental health services. However, few longitudinal studies examined subjects during incarceration or detention. This study compares depressive symptoms, abnormal eating behaviour and impulsivity before release from a detention centre and after incarceration, thereby indicating the effectiveness of psychiatric intervention in a Japanese detention centre. Method: Of 64 young women, 36 were followed up. Self-report measures were used to assess depression, eating behaviour and impulsivity after incarceration and one month before release. Results: Of the 36 participants, nine were diagnosed using the MINI-kids as needing mental health services. Those who received psychiatric intervention were diagnosed as having major depression and/or post-traumatic stress disorder. Significant main effects of intervention and effects of time were shown in the DSD. The EAT-26 score demonstrated the significance of the effects of time and interaction. In the BIS-11 scores, neither intervention nor time showed significant effects. Conclusions: Results of this study showed that the time course and psychiatric intervention contributed to recovery of depression and therapeutic intervention. The time course might reduce eating problems. Psychiatric intervention might be necessary for female juvenile detainees, which presents an important issue for future studies.
Insecurity of young people
Authors: Vornanen Riitta , Törrönen Maritta , Niemelä Pauli 
Published: October 2009

This article critically examines the concept of insecurity as experienced by young people in Finland. Young people’s own definitions of insecurity show how 13–17-year-olds assess their lives and ontological insecurities and threats in the world. The topic is analyzed from a social sciences perspective and interpreted within the theoretical framework of risk society by Ulrich Beck (1996; 2001), Anthony Giddens (1991) and Franz-Xavier Kaufmann (1970). The data was collected from schools in five regions in Finland. A total of 922 respondents aged 13 to 17 completed a questionnaire in classroom settings. This article analyzes only the data elicited by open-ended questions, which were answered by 683 young people. Young people’s experiences of insecurity were classified into 16 categories, which were then divided under three headings: (i) the inner circle, that is, insecurity related to personal emotions and inner experiences; (ii) the social circle, that is, insecurity related to social interaction; and (iii) the outer circle, that is, insecurity related to external realities. Young people’s definitions of insecurity reveal their perspective on risk society in which everyone is vulnerable to certain risks.The answers disclose a set of contradictory risks, which are at the same time personal, local and global. First, they connect insecurity to their inner feelings and emotions. Second, they interpret the social relationships and the everyday life experiences in connection with insecurity. Third, insecurity is defined by young people by external realities, such as socio-economic ill-being, violence and war. In the future, more empirical and qualitative research on risk society and how it is experienced by young people in the everyday life is needed. How do young people connect close and distant security issues and insecurity to their everyday life?
The effect of the tachykinin NK2 receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics
Authors: Schelfhout Venessa , Van De Velde Veerle , Maggi Carlo , Pauwels Romain , Joos Guy 
Published: October 2009

Objective: We previously reported that the nonpeptide tachykinin NK2 receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK2 receptor antagonist. The aim of the trial was to examine the effect of nepadutant on neurokinin A-induced bronchoconstriction in man. Methods: 12 patients with stable, mild to moderate asthma participated in a double-blind, placebo-controlled crossover trial and received, with intervals of 1 week, MEN11420 2 mg, MEN11420 8 mg and placebo (i.v.). Increasing concentrations of NKA (10-9 to 10-6 moles/ml) were inhaled immediately after (d1) and 24 hours after (d2) administration of treatment. Results: On d1 both MEN11420 2 and 8 mg shifted the dose response curve for neurokinin A to the right (log PC20 FEV1 neurokinin A [moles/ml]; mean± SEM -6.38±0.26 after 2 mg, -6.11±0.23 after 8 mg, versus -6.95±0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction. Conclusion: In conclusion, the tachykinin NK2 receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.
A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma
Authors: Lokhorst Henk M. , van der Holt Bronno , Zweegman Sonja , Vellenga Edo , Croockewit Sandra , van Oers Marinus H. , von dem Borne Peter , Wijermans Pierre , Schaafsma Ron , de Weerdt Okke , Wittebol Shulamiet , Delforge Michel , Berenschot Henriëtte , Bos Gerard M. , Jie Kon-Siong G. , Sinnige Harm , van Marwijk-Kooy Marinus , Joosten Peter , Minnema Monique C. , van Ammerlaan Rianne , Sonneveld Pieter ,   for Dutch-Belgian Hemato-Oncology Group (HOVON)
Published: October 2009

Abstract
The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m2, followed by maintenance with α-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.
Methods for therapeutic trials in COPD: lessons from the TORCH trial
Authors: Keene O. N. , Vestbo J. , Anderson J. A. , Calverley P. M. A. , Celli B. , Ferguson G. T. , Jenkins C. , Jones P. W. 
Published: October 2009

The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation.When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments.The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study.Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.
Global gene expression patterns in the post-pneumonectomy lung of adult mice
Authors: Paxson Julia A , Parkin Christopher D , Iyer Lakshmanan K , Mazan Melissa R , Ingenito Edward P , Hoffman Andrew M 
Published: October 2009

Abstract

Background
Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.

Methods
Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.

Results
The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.

Conclusion
These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.
Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells
Authors: Fernández-Sánchez Marcela , del Castillo-Vaquero Angel , Salido Ginés M , González Antonio 
Published: October 2009

Abstract

Background
A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively.

Results
Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production.

Conclusion
ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.
Pollen development in Annona cherimola Mill. (Annonaceae). Implications for the evolution of aggregated pollen
Authors: Lora Jorge , Testillano Pilar S , Risueño Maria C , Hormaza Jose I , Herrero Maria 
Published: October 2009

AbstractBackgroundIn most flowering plants, pollen is dispersed as monads. However, aggregated pollen shedding in groups of four or more pollen grains has arisen independently several times during angiosperm evolution. The reasons behind this phenomenon are largely unknown. In this study, we followed pollen development inAnnona cherimola, a basal angiosperm species that releases pollen in groups of four, to investigate how pollen ontogeny may explain the rise and establishment of this character. We followed pollen development using immunolocalization and cytochemical characterization of changes occurring from anther differentiation to pollen dehiscence.ResultsOur results show that, following tetrad formation, a delay in the dissolution of the pollen mother cell wall and tapetal chamber is a key event that holds the four microspores together in a confined tapetal chamber, allowing them to rotate and then bind through the aperture sites through small pectin bridges, followed by joint sporopollenin deposition.ConclusionPollen grouping could be the result of relatively minor ontogenetic changes beneficial for pollen transfer or/and protection from desiccation. Comparison of these events with those recorded in the recent pollen developmental mutants in Arabidopsis indicates that several failures during tetrad dissolution may convert to a common recurring phenotype that has evolved independently several times, whenever this grouping conferred advantages for pollen transfer.
Comparison of breast cancer survival in two populations: Ardabil, Iran and British Columbia, Canada
Authors: Sadjadi Alireza , Hislop T Gregory , Bajdik Chris , Bashash Morteza , Ghorbani Anahita , Nouraie Mehdi , Babaei Masoud , Malekzadeh Reza , Yavari Parvin 
Published: October 2009

Abstract

Background
Patterns in survival can provide information about the burden and severity of cancer, help uncover gaps in systemic policy and program delivery, and support the planning of enhanced cancer control systems. The aim of this paper is to describe the one-year survival rates for breast cancer in two populations using population-based cancer registries: Ardabil, Iran, and British Columbia (BC), Canada.

Methods
All newly diagnosed cases of female breast cancer were identified in the Ardabil cancer registry from 2003 to 2005 and the BC cancer registry for 2003. The International Classification of Disease for Oncology (ICDO) was used for coding cancer morphology and topography. Survival time was determined from cancer diagnosis to death. Age-specific one-year survival rates, relative survival rates and weighted standard errors were calculated using life-tables for each country.

Results
Breast cancer patients in BC had greater one-year survival rates than patients in Ardabil overall and for each age group under 60.

Conclusion
These findings support the need for breast cancer screening programs (including regular clinical breast examinations and mammography), public education and awareness regarding early detection of breast cancer, and education of health care providers.
Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2genes in yeast
Authors: Vogelsang Matjaz , Comino Aleksandra , Zupanec Neja , Hudler Petra , Komel Radovan 
Published: October 2009

Abstract

Background
Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells.

Methods
Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested.

Results
The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic.

Conclusion
Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.
The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease
Authors: Farcas Monica A , Rouleau Leonie , Fraser Richard , Leask Richard L 
Published: October 2009

Abstract
The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process.