bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of etanercept treatment in early active rheumatoid arthritis followed by dose adjustment
Authors: Kobelt Gisela , Lekander Ingrid , Lang Andrea , Raffeiner Bernd , Botsios Costantino , Geborek Pierre 
Published: July 2011

Objectives: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.Methods: Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.Results: The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective.Conclusions and Policy Implications: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment.
Methylphenidate delivery mechanisms for the treatment of children with attention deficit hyperactivity disorder: Heterogeneity in parent preferences
Authors: Lloyd Andrew , Hodgkins Paul , Dewilde Sarah , Sasané Rahul , Falconer Shona , Sonuga Barke Edmund 
Published: July 2011

Objectives:Extended-release therapies avoid the need for children with attention-deficit/hyperactivity disorder (ADHD) to take medication at school. Recently a transdermal delivery system has been developed which can allow symptom control all day long but with greater dosing flexibility. This study explored the parents' preferences regarding oral and transdermal therapy.Methods:A nonsystematic and qualitative literature review and in-depth interviews with parents and physicians helped identify salient treatment attributes for a discrete choice experiment. Treatment attributes included mode of administration (tablet or transdermal), speed of onset (30–90 min); duration (lasts until 3–9pm) and ability to tailor the drug to different needs (no flexibility, limited flexibility, easy to adjust to different days). A convenience sample of parents of children treated for ADHD (n= 200) were recruited using a recruitment agency. Data were analyzed using generalized estimating equations (GEE).Results:Parents' preferred once-a-day oral therapy (odds ratio [OR] = 1.76 [95 percent confidence interval {CI}, 1.43 – 2.18]); rapid speed of onset (OR = 1.22 [95 percent CI, 1.07 – 1.39]), and symptom control until 9pm(OR = 3.79 [95 percent CI, 2.98 – 4.82]). Analyses identified that 30 percent of parents preferred transdermal treatment and this subgroup preferred treatments with a fast onset of action.Conclusions:This survey demonstrates that parents of ADHD children have different preferences for the ADHD treatments prescribed for their children. A distinct subgroup of parents prefer the transdermal therapy. These parents were less likely to be working and so monitoring compliance and doing after school activities may have been easier.
Mapping the increasing risk of human alveolar echinococcosis in Limburg, The Netherlands
Authors: TAKUMI K. , HEGGLIN D. , DEPLAZES P. , GOTTSTEIN B. , TEUNIS P. , VAN DER GIESSEN J. 
Published: July 2011

SUMMARYThe parasite Echinococcus multilocularis was first detected in The Netherlands in 1996 and repeated studies have shown that the parasite subsequently spread in the local population of foxes in the province of Limburg. It was not possible to quantify the human risk of alveolar echinococcosis because no relationship between the amount of parasite eggs in the environment and the probability of infection in humans was known. Here, we used the spread of the parasite in The Netherlands as a predictor, together with recently published historical records of the epidemiology of alveolar echinococcosis in Switzerland, to achieve a relative quantification of the risk. Based on these analyses, the human risk in Limburg was simulated and up to three human cases are predicted by 2018. We conclude that the epidemiology of alveolar echinococcosis in The Netherlands might have changed from a period of negligible risk in the past to a period of increasing risk in the forthcoming years.
Molecular typing of adenovirus circulating in a Colombian paediatric population with acute respiratory infection
Authors: ROJAS L. J. , JARAMILLO C. A. , MOJICA M. F. , ESCALANTE M. P. , DELGADO P. 
Published: July 2011

SUMMARYHuman adenoviruses (HAdV) cause a broad spectrum of diseases including acute respiratory infection (ARI), and are responsible for 5% of cases requiring hospitalization in children aged <5 years in Colombia; however, little is known about the circulating types, partly due to the lack of reliable typing tests. In order to evaluate a VA gene PCR-sequencing approach for identification of HAdV circulating types in a Colombian population, 52 nasopharyngeal aspirates/swabs from children with ARI were processed. After a BLAST analysis, matches with species B (41/48, 85·42%), C (6/48, 12·5%), and D (1/48, 2·08%) were found; and at the type level, type 3 (22/48, 45·83%) was the most frequent. This initial effort to expand our knowledge about the molecular epidemiology of HAdV circulating in Bogota, Colombia, showed that HAdV-B was the predominant circulating species in the study period and reports, for the first time in Colombia, the presence of HAdV-D in a respiratory sample.
Understanding the dermal light sense in the context of integrative photoreceptor cell biology
Authors: DESMOND RAMIREZ M. , SPEISER DANIEL I. , SABRINA PANKEY M. , OAKLEY TODD H. 
Published: July 2011

AbstractWhile the concept of a dermal light sense has existed for over a century, little progress has been made in our understanding of the mechanisms underlying dispersed photoreception and the evolutionary histories of dispersed photoreceptor cells. These cells historically have been difficult to locate and positively identify, but modern molecular techniques, integrated with existing behavioral, morphological, and physiological data, will make cell identification easier and allow us to address questions of mechanism and evolution. With this in mind, we propose a new classification scheme for all photoreceptor cell types based on two axes, cell distribution (aggregatedvs.dispersed) and position within neural networks (first ordervs.high order). All photoreceptor cells fall within one of four quadrants created by these axes: aggregated/high order, dispersed/high order, aggregated/first order, or dispersed/first order. This new method of organization will help researchers make objective comparisons between different photoreceptor cell types. Using integrative data from four major phyla (Mollusca, Cnidaria, Echinodermata, and Arthropoda), we also provide evidence for three hypotheses for dispersed photoreceptor cell function and evolution. First, aside from echinoderms, we find that animals often use dispersed photoreceptor cells for tasks that do not require spatial vision. Second, although there are both echinoderm and arthropod exceptions, we find that dispersed photoreceptor cells generally lack morphological specializations that either enhance light gathering or aid in the collection of directional information about light. Third, we find that dispersed photoreceptor cells have evolved a number of times in Metazoa and that most dispersed photoreceptor cells have likely evolved through the co-option of existing phototransduction cascades. Our new classification scheme, combined with modern investigative techniques, will help us address these hypotheses in great detail and generate new hypothesis regarding the function and evolution of dispersed photoreceptor cells.
Infectious Rats and Dangerous Cows: Transnational Perspectives on Animal Diseases in the First Half of the Twentieth Century
Authors: KNAB CORNELIA 
Published: July 2011

AbstractFrom the late nineteenth century onwards, the danger of animal diseases crossing national borders became increasingly apparent. The vast increase in the global trade in animals and animal products turned such diseases into a threat to both economic relations and public health, and called for international attention. Governments and groups of transnational experts began to develop cross-border networking strategies to counter the spread of animal diseases. Significant new developments started after the First World War with the establishment of a number of international animal health institutions, along with the Office International des Epizooties in Paris and the Veterinary Subcommittees of the League of Nations. This article traces the work of these two international animal health agencies and the interaction between their role as intergovernmental platforms and their capacity to define their own terms of reference.
Maps of protein structure space reveal a fundamental relationship between protein structure and function
Authors: Osadchy Margarita , Kolodny Rachel 
Published: July 2011

To study the protein structure–function relationship, we propose a method to efficiently create three-dimensional maps of structure space using a very large dataset of > 30,000 Structural Classification of Proteins (SCOP) domains. In our maps, each domain is represented by a point, and the distance between any two points approximates the structural distance between their corresponding domains. We use these maps to study the spatial distributions of properties of proteins, and in particular those of local vicinities in structure space such as structural density and functional diversity. These maps provide a unique broad view of protein space and thus reveal previously undescribed fundamental properties thereof. At the same time, the maps are consistent with previous knowledge (e.g., domains cluster by their SCOP class) and organize in a unified, coherent representation previous observation concerning specific protein folds. To investigate the function–structure relationship, we measure the functional diversity (using the Gene Ontology controlled vocabulary) in local structural vicinities. Our most striking finding is that functional diversity varies considerably across structure space: The space has a highly diverse region, and diversity abates when moving away from it. Interestingly, the domains in this region are mostly alpha/beta structures, which are known to be the most ancient proteins. We believe that our unique perspective of structure space will open previously undescribed ways of studying proteins, their evolution, and the relationship between their structure and function.
THE GUEST FROM ENGLAND: EXPLORING ISSUES OF POSITIONALITY IN A FOREIGN AND YET FAMILIAR SETTING
Authors: Jones Marion 
Published: July 2011

ABSTRACT
By adopting a reflective–reflexive approach, the paper explores aspects of positionality in relation to gender and culture and examines in what way they affect the generation of status and power within the relationships and social interactions of the research participants. By drawing on my personal experience as a female researcher operating in a male-dominated, foreign and yet familiar setting, I will analyse the mechanisms involved in the negotiation of the positions occupied by the various players and how this determined my status in terms of insider/outsidership. Particular attention will be paid to the facilitation of access to the field and the construction of knowledge. The data informing this paper were collected as part of a study of school-based models of initial teacher training in Germany, including contributions from the directors, tutors and mentors of three teacher training Seminars as well as my own observations. The relatively small sample of respondents and the researcher's subjective perspective of reporting and interpreting the findings preclude any conclusions of a general nature to be drawn. However, interesting data emerged, suggesting that aspects of gender and culture as well as the researcher's biographical background constitute powerful factors in the positioning of the research participants, which have methodological and epistemological implications. In the light of these findings I would argue that by adopting a reflective–reflexive approach the quality of the research account can be enhanced by making the mechanisms involved in the negotiation of positions of power and control more transparent. Finally, the analysis presented is intended to act as a caveat against the simplistic assumption that a researcher's familiarity and biographical affiliation with the setting will assist him/her in establishing and maintaining control over the research process.
Functional Analysis of Two Isoforms of Leaf-Type Ferredoxin-NADP+-Oxidoreductase in Rice Using the Heterologous Expression System of Arabidopsis
Authors: Higuchi-Takeuchi Mieko , Ichikawa Takanari , Kondou Youichi , Matsui Keiko , Hasegawa Yukako , Kawashima Mika , Sonoike Kintake , Mori Masaki , Hirochika Hirohiko , Matsui Minami 
Published: July 2011

Abstract
Ferredoxin-NADP+-oxidoreductase (FNR) mediates electron transfer between ferredoxin (Fd) and NADP+; therefore, it is a key enzyme that provides the reducing power used in the Calvin cycle. Other than FNR, nitrite reductase, sulfite reductase, glutamate synthase, and Fd-thioredoxin reductase also accept electrons from Fd, an electron carrier protein in the stroma. Therefore, the regulation of electron partitioning in the chloroplast is important for photosynthesis and other metabolic pathways. The regulatory mechanism of electron partitioning, however, remains to be elucidated. We found, by taking advantage of a gain-of-function approach, that expression of two rice (Oryza sativa) full-length cDNAs of leaf-type FNRs (OsLFNR1 and OsLFNR2) led to altered chlorophyll fluorescence and growth in Arabidopsis (Arabidopsis thaliana) and rice. We revealed that overexpression of the OsLFNR1 and OsLFNR2 full-length cDNAs resulted in distinct phenotypes despite the high sequence similarity between them. Expression of OsLFNR1 affected the nitrogen assimilation pathway without inhibition of photosynthesis under normal conditions. On the other hand, OsLFNR2 expression led to the impairment of photosynthetic linear electron transport as well as Fd-dependent cyclic electron flow around photosystem I. The endogenous protein level of OsLFNR was found to be suppressed in both OsLFNR1- and OsLFNR2-overexpressing rice plants, leading to changes in the stoichiometry of the two LFNR isoforms within the thylakoid and soluble fractions. Thus, we propose that the stoichiometry of two LFNR isoforms plays an important role in electron partitioning between carbon fixation and nitrogen assimilation.
Clinical Immunology Review Series: An approach to the patient with a periodic fever syndrome
Authors: Lachmann H J 
Published: July 2011

SummaryThe periodic fever syndromes are disorders of innate immunity. They may be inherited or acquired and present as recurrent attacks of apparently spontaneous self-limiting inflammation without evidence of autoantibodies or infection. Over the past decade-and-a-half there has been significant progress in their understanding and treatment.
Visit‐to‐visit variability in blood pressure strongly predicts all‐cause mortality in patients with type 2 diabetes: a 5·5‐year prospective analysis
Authors: Hsieh Yi‐Ting , Tu Shih‐Te , Cho Tzu‐Jung , Chang Shun‐Jen , Chen Jung‐Fu , Hsieh Ming‐Chia 
Published: July 2011

Eur J Clin Invest 2012; 42 (3): 245–253AbstractBackground  Elevations in blood pressure and visit‐to‐visit variability have been found to significantly increase the risk of cardiovascular morbidity and mortality in nondiabetic individuals. This study has assessed the association between all‐cause mortality and blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP) and visit‐to‐visit variability] in patients with type 2 diabetes.Materials and methods  A longitudinal cohort study of 2161 patients with type 2 diabetes and a mean follow‐up period of 66·7 ± 7·5 months. Using Cox regression models, blood pressure parameters were related to the risk of all‐cause mortality.Results  Visit‐to‐visit variability in SBP [HR: 1·048 (95% CI: 1·005–1·092; P = 0·03)], DBP [HR: 1·090 (95% CI: 1·021–1·163; P = 0·01)] and MAP [HR: 1·099 (95% CI: 1·033–1·170; P = 0·003)] significantly predicted all‐cause mortality in patients with type 2 diabetes after adjusting for baseline data, mean follow‐up blood pressure profiles and HbA1c. Visit‐to‐visit variability in PP [HR: 1·139 (95% CI: 1·030–1·258; P = 0·01)] significantly predicted cardiovascular mortality. Neither baseline nor follow‐up SBP, DBP, PP nor MAP was significantly associated with all‐cause and cardiovascular mortality after adjusting for blood pressure variability. The risk of all‐cause mortality with a mean follow‐up SBP has a U‐shaped distribution. Patients with a mean follow‐up DBP > 90 mmHg were at higher risk of mortality than those with DBP < 90 mmHg.Conclusions  Visit‐to‐visit variability in blood pressure was significantly associated with all‐cause mortality independent of mean BP in patients with type 2 diabetes. The data for blood pressure variability might be regarded as a potentially important therapeutic target in the management of type 2 diabetes.
Breakage of the nuclear envelope by an extending mitotic nucleus occurs during anaphase in Schizosaccharomyces japonicus
Authors: Aoki Keita , Hayashi Hanako , Furuya Kanji , Sato Mamiko , Takagi Tomoko , Osumi Masako , Kimura Akatsuki , Niki Hironori 
Published: July 2011

During open mitosis in higher eukaryotic cells, the nuclear envelope completely breaks down and then mitotic chromosomes are exposed in the cytoplasm. By contrast, mitosis in lower eukaryotes, including fungi, proceeds with the nucleus enclosed in an intact nuclear envelope. The mechanism of mitosis has been studied extensively in yeast, a closed mitosis organism. Here, we describe a form of mitosis in which the nuclear envelope is torn by elongation of the nucleus in the fission yeast Schizosaccharomyces japonicus. The mitotic nucleus of Sz. japonicus adopted a fusiform shape in anaphase, and its following extension caused separation. Finally, a tear in the nuclear envelope occurred in late anaphase. At the same time, a polarized‐biased localization of nuclear pores was seen in the fusiform‐shaped nuclear envelope, suggesting a compromise in the mechanical integrity of the lipid membrane. It has been known that nuclear membrane remains intact in some metazoan mitosis. We found that a similar tear of the nuclear envelope was also observed in late mitosis of the Caenorhabditis elegans embryo. These findings provide insight into the diversity of mitosis and the biological significance of breakdown of the nuclear envelope.
Effects of Trypanosoma cruzi infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats
Authors: Novaes Rômulo D. , Penitente Arlete R. , Gonçalves Reggiani V. , Talvani André , Neves Clóvis A. , Maldonado Izabel R. S. C. , Natali Antônio J. 
Published: July 2011

SummaryThe aim of this study was to investigate the effects of Trypanosoma cruzi (T. cruzi) infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats. Adult Wistar rats were randomized into control (n = 14) and infected (n = 14) groups. Infected animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes/50 g body weight). After 9 weeks, the animals were subjected to a treadmill running protocol. Then, the right atrium (RA) and left ventricle (LV) were removed for morphological and cell contractile evaluation. The infected animals exhibited a significant reduction in distance travelled, total time to fatigue and workload. In addition, these animals had hypertrophy, increased myocardial cellularity, and an increase in the proportion of collagen and blood vessels. RA and LV myocytes from infected animals showed marked contractile dysfunction under basal conditions and a reduced contractile response to β‐adrenergic stimulation. The workload of infected animals was correlated closely with the amplitude of cell shortening of RA and LV myocytes. T. cruzi infection influenced the myocardial morphology and the mechanical properties of RA and LV single myocytes negatively and reduced exercise tolerance. Single cardiomyocyte contractile dysfunction could constitute an additional mechanism of cardiac impairment and reduced exercise tolerance in this infection.
Simple nutritional intervention in patients with advanced cancers of the gastrointestinal tract, non‐small cell lung cancers or mesothelioma and weight loss receiving chemotherapy: a randomised controlled trial
Authors: Baldwin C. , Spiro A. , McGough C. , Norman A. R. , Gillbanks A. , Thomas K. , Cunningham D. , O’Brien M. , Andreyev H. J. N. 
Published: July 2011

AbstractBackground:  Weight loss in patients with cancer is common and associated with a poorer survival and quality of life. Benefits from nutritional interventions are unclear. The present study assessed the effect of dietary advice and/or oral nutritional supplements on survival, nutritional endpoints and quality of life in patients with weight loss receiving palliative chemotherapy for gastrointestinal and non‐small cell lung cancers or mesothelioma.Methods:  Participants were randomly assigned to receive no intervention, dietary advice, a nutritional supplement or dietary advice plus supplement before the start of chemotherapy. Patients were followed for 1 year. Survival, nutritional status and quality of life were assessed.Results:  In total, 256 men and 102 women (median age, 66 years; range 24–88 years) with gastrointestinal (n = 277) and lung (n = 81) cancers were recruited. Median (range) follow‐up was 6 (0–49) months. One‐year survival was 38.6% (95% confidence interval 33.3–43.9). No differences in survival, weight or quality of life between groups were seen. Patients surviving beyond 26 weeks experienced significant weight gain from baseline to 12 weeks, although this was independent of nutritional intervention.Conclusions:  Simple nutritional interventions did not improve clinical or nutritional outcomes or quality of life. Weight gain predicted a longer survival but occurred independently of nutritional intervention.