bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia
Authors: Kreil Sebastian , Pfirrmann Markus , Haferlach Claudia , Waghorn Katherine , Chase Andrew , Hehlmann Rüdiger , Reiter Andreas , Hochhaus Andreas , Cross Nicholas C. P. 
Published: April 2007

Abstract
Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic myelogenous leukemia and have been associated with a poor prognosis; however, no studies have been performed in the context of a randomized clinical trial. We developed a DNA-based deletion screen and investigated 339 chronic phase patients treated with interferon-α as first-line therapy in 3 controlled German studies with a median observation time of 7 years. Deletions were detected in pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the breakpoint. There was no significant difference in overall survival between deleted and nondeleted patients. Patients with breakpoint-spanning deletions had poorer survival compared with patients without deletions (4.7 versus 7.8 years; P = .003), but this was not significant when censored at allogeneic stem cell transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were associated with improved survival compared with cases without deletions (P = .001). Multiple Cox regression analysis indicated that deletion status (P = .007), age (P = .018), and spleen enlargement (P < .001) were significant independent indicators of survival and confirmed that only deletions spanning the ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).
A Familial Thyrotropin (TSH) Receptor Mutation Provides in Vivo Evidence that the Inositol Phosphates/Ca2+ Cascade Mediates TSH Action on Thyroid Hormone Synthesis
Authors: Grasberger Helmut , Van Sande Jacqueline , Hag-Dahood Mahameed Ahmad , Tenenbaum-Rakover Yardena , Refetoff Samuel 
Published: April 2007

AbstractContext: In the human thyroid gland, TSH activates both the cAMP and inositol phosphates (IP) signaling cascades via binding to the TSH receptor (TSHR). Biallelic TSHR loss-of-function mutations cause resistance to TSH, clinically characterized by hyperthyrotropinemia, and normal or reduced thyroid gland volume, thyroid hormone output, and iodine uptake.Objective: We report and study a novel familial TSHR mutation (L653V).Results: Homozygous individuals expressing L653V had euthyroid hyperthyrotropinemia. Paradoxically, patients had significantly higher 2-h radioiodide uptake and 2- to 24-h radioiodide uptake ratios compared with heterozygous, unaffected family members, suggesting an imbalance between iodide trapping and organification. In transfected COS-7 cells, the mutant TSHR had normal surface expression, basal activity, and TSH-binding affinity, equally (2.2-fold) increased EC50 values for TSH-induced cAMP and IP accumulation, and normal maximum cAMP generation. In contrast, the efficacy of TSH for generating IP was more than 7-fold lower with the mutant compared with wild-type TSHR.Conclusions: We identified and characterized a TSHR defect, preferentially affecting the IP pathway, with a phenotype distinct from previously reported loss-of-function mutations. Results provide the first in vivo evidence for the physiological role of the TSHR/IP/Ca2+ cascade in regulating iodination. According to systematic in vitro mutagenesis studies, other TSHR mutations can result in even complete loss of IP signaling with retained cAMP induction. We hypothesize that such TSHR mutations could be the cause in unexplained partial organification defects.
Receptor Interacting Protein 140 Regulates Expression of Uncoupling Protein 1 in Adipocytes through Specific Peroxisome Proliferator Activated Receptor Isoforms and Estrogen-Related Receptor α
Authors: Debevec Darja , Christian Mark , Morganstein Daniel , Seth Asha , Herzog Birger , Parker Malcolm , White Roger 
Published: April 2007

AbstractExpression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated adipocytes derived from brown or white adipose tissue devoid of the nuclear receptor corepressor receptor interacting protein 140 (RIP140). Increased expression is mediated in part by the recruitment of peroxisome proliferator activated receptors α and γ, together with estrogen-related receptor α, which functions through a novel binding site on the Ucp1 enhancer. This demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves derepression of at least three different nuclear receptors. The ability to increase expression of Ucp1 by β-adrenergic signaling is independent of RIP140, as shown by the action of the β3-adrenergic agonist CL 316,243 to stimulate expression in both brown and white adipocytes in the presence and absence of the corepressor. Therefore, the expression of this metabolic uncoupling protein in adipose cells is regulated by inhibition as well as activation of distinct signaling pathways.
Experimental validation of a finite element model of a composite tibia
Authors: Gray H A , Zavatsky A B , Taddei F , Cristofolini L , Gill H S 
Published: April 2007

Composite bones are synthetic models made to simulate the mechanical behaviour of human bones. Finite element (FE) models of composite bone can be used to evaluate new and modified designs of joint prostheses and fixation devices. The aim of the current study was to create an FE model of a composite tibia and to validate it against results obtained from a comprehensive set of experiments. For this, 17 strain rosettes were attached to a composite tibia (model 3101, Pacific Research Laboratories, Vashon, Washington, USA). Surface strains and displacements were measured under 13 loading conditions. Two FE models were created on the basis of computed tomography scans. The models differed from each other in the mesh and material properties assigned. The experiments were simulated on them and the results compared with experimental results. The more accurate model was selected on the basis of regression analysis. In general, experimental strain measurements were highly repeatable and compared well with published results. The more accurate model, in which the inner elements representing the foam were assigned isotropic material properties and the elements representing the epoxy layer were assigned transversely isotropic material properties, was able to simulate the mechanical behaviour of the tibia with acceptable accuracy. The regression line for all axial loads combined had a slope of 0.999, an intercept of -6.24 microstrain, and an R2 value of 0.962. The root mean square error as a percentage was 5 per cent.
An Exact Approach for the Vehicle Routing Problem with Two-Dimensional Loading Constraints
Authors: Iori Manuel , Salazar-González Juan-José , Vigo Daniele 
Published: April 2007

We consider a special case of the symmetric capacitated vehicle routing problem, in which a fleet of K identical vehicles must serve n customers, each with a given demand consisting in a set of rectangular two-dimensional weighted items. The vehicles have a two-dimensional loading surface and a maximum weight capacity. The aim is to find a partition of the customers into routes of minimum total cost such that, for each vehicle, the weight capacity is taken into account and a feasible two-dimensional allocation of the items into the loading surface exists. The problem has several practical applications in freight transportation, and it is 𝒩𝒫-hard in the strong sense. We propose an exact approach, based on a branch-and-cut algorithm, for the minimization of the routing cost that iteratively calls a branch-and-bound algorithm for checking the feasibility of the loadings. Heuristics are also used to improve the overall performance of the algorithm. The effectiveness of the approach is shown by means of computational results.
Computer navigation versus conventional total knee replacement
Authors: Spencer J. M. , Chauhan S. K. , Sloan K. , Taylor A. , Beaver R. J. 
Published: April 2007

We previously compared the component alignment in total knee replacement using a computer-navigated technique with a conventional jig-based method. We randomly allocated 71 patients to undergo either computer-navigated or conventional replacement. An improved alignment was seen in the computer-navigated group. The patients were then followed up post-operatively for two years, using the Knee Society score, the Short Form-36 health survey, the Western Ontario and McMaster Universities osteoarthritis index, the Bartlett Patellar pain questionnaire and the Oxford knee score, to assess functional outcome. At two years post-operatively 60 patients were available for assessment, 30 in each group and 62 patients completed a postal survey. No patient in either group had undergone revision. All variables were analysed for differences between the groups either by Student’s t-test or the Mann-Whitney U test. Differences between the two groups did not reach significance for any of the outcome measures at any time point. At two years postoperatively, the frequency of mild to severe anterior pain was not significantly different (p = 0.818), varying between 44% (14) for the computer-navigated group, and 47% (14) for the conventionally-replaced group. The Bartlett Patellar score and the Oxford knee score were also not significantly different (t-test p = 0.161 and p = 0.607, respectively). The clinical outcome of the patients with a computer-navigated knee replacement appears to be no different to that of a more conventional jig-based technique at two years post-operatively, despite the better alignment achieved with computer-navigated surgery.
Alignment and orientation of the components in total knee replacement with and without navigation support
Authors: Kim Y.-H. , Kim J.-S. , Yoon S.-H. 
Published: April 2007

Bilateral sequential total knee replacement was carried out under one anaesthetic in 100 patients. One knee was replaced using a CT-free computer-assisted navigation system and the other conventionally without navigation. The two methods were compared for accuracy of orientation and alignment of the components. There were 85 women and 15 men with a mean age of 67.6 years (54 to 83). Radiological and CT imaging was carried out to determine the alignment of the components. The mean follow-up was 2.3 years (2 to 3). The operating and tourniquet times were significantly longer in the navigation group (p < 0.001). There were no significant pre- or post-operative differences between the knee scores of the two groups (p = 0.288 and p = 0.429, respectively). The results of imaging and the number of outliers for all radiological parameters were not statistically different (p = 0.109 to p = 0.920). In this series computer-assisted navigated total knee replacement did not result in more accurate orientation and alignment of the components than that achieved by conventional total knee replacement.
Cardiology: Aspirin Resistance in Patients with Stable Coronary Artery Disease with and without a History of Myocardial Infarction
Authors: Dorsch Michael P , Lee Jin Sun , Lynch Donald R , Dunn Steven P , Rodgers Jo E , Schwartz Todd , Colby Emily , Montague Debbie , Smyth Susan S 
Published: April 2007

Background: Aspirin therapy is a cornerstone in the prevention of atherothrombotic events, but recurrent vascular events are estimated to occur in 8-18% of patients taking aspirin for secondary prevention after 2 years. Estimates of biologic aspirin resistance vary from 5% to 60%, depending on the assay used. However, the relationship between biologic measurements of aspirin resistance and adverse clinical events remains unclear. Objective: To determine whether patients with documented myocardial infarction (Ml) while on aspirin therapy (cases) were more likely to be aspirin resistant than were patients with coronary artery disease (CAD) who had no history of Ml (controls) and to assess clinical predictors of aspirin resistance in patients with stable CAD. Methods: This case-control study examined aspirin responses using the VerifyNow Aspirin Assay system in 50 cases and 50 controls who had taken a dose of aspirin within 48 hours of presentation to the clinic visit. Odds ratios were estimated to determine the association between aspirin resistance and MI, Independent predictors of aspirin resistance were determined using univariate and multivariate analyses. Results: An increase in the prevalence of aspirin resistance among cases (16% vs 12% in controls) was not observed (OR 1.40; 95% CI 0.45 to 4.37; p = 0.566). In the overall CAD population, female sex was independently associated with aspirin resistance (OR 4.01; 95% CI 1.15 to 13.92; p = 0.029). Conclusions: Additional large studies are required to understand whether biologically defined aspirin resistance is associated with increased risk for cardiovascular events, with special attention paid to sex differences.
Use of Bone Health Protocol to Identify and Prevent Bone Disease in Kidney and Pancreas Transplant Recipients
Authors: Taber David J , Ashcraft Elizabeth A , Baillie G Mark , Lawrence D Bart , Chavin Kenneth D , Baliga Prabhakar K 
Published: April 2007

BACKGROUND: Posttransplant bone disease is a well recognized and under-treated problem. The use of protocols within other populations has been shown to improve recognition and treatment of common disease states, but outcome studies involving the use of protocols within transplant patients are lacking. OBJECTIVE: To compare the appropriate screening for and the prevention and treatment of osteopenia and osteoporosis in transplant patients before and after a bone health protocol was implemented. METHODS: A retrospective analysis in a single institution was designed to determine whether the development and implementation of a comprehensive bone health protocol impacted disease outcomes in posttransplant kidney and simultaneous kidney—pancreas patients. RESULTS: There were 132 patients in the historical control group and 76 in the treatment group. The groups were well matched, with no statistically significant differences noted for any of the baseline characteristics that were compared, including the modifiable and nonmodifiable risk factors known to put a patient at increased risk for osteopenia or osteoporosis. Significantly more patients in the treatment group received proper screening and prevention compared with the historical control group (p < 0.001). Although more patients in the treatment group received proper bone disease treatment, this did not reach statistical significance (81% vs 66%; p < 0.22). Additionally, the dual energy X-ray absorptiometry scans were performed, on average, 19 days earlier in the treatment group, although this also did not achieve statistical significance (p = 0.149). CONCLUSIONS: The multidisciplinary development and implementation of a comprehensive bone health protocol improves the screening and prevention of osteopenia and osteoporosis within kidney and pancreas transplant recipients. TRASFONDO: La enfermedad ósea luego de un transplante de órganos es un problema conocido y que no es tratado adecuadamente. La utilización de protocolos en otras poblaciones ha demostrado mejorar el reconocimiento y tratamiento de enfermedades comunes pero no hay suficientes estudios de los resultados del uso de protocolos en pacientes con transplante de órganos.
Helping Relationships and Genetic Propensities: A Combinatoric Study of DRD2, Mentoring, and Educational Continuation
Authors: Shanahan Michael J. , Erickson Lance D. , Vaisey Stephen , Smolen Andrew 
Published: April 2007

AbstractFrom conception to death, helping relationships promote positive development and enable people to surmount challenges in their lives. Is it the case that the negative consequences of a genetic propensity for risky behaviors can be attenuated by helping relationships (a G × E)? But is it also the case that people with such a genetic propensity are less likely to have helping relationships compared to people without such a propensity (a rGE)? We illustrate this complex pattern of gene–environment interplay by drawing on the National Longitudinal Study of Adolescent Health and a combinatoric analytic strategy. We focus on a gene associated with dopamine receptor type 2 (DRD2 TaqIA), student–mentor relationships, and educational continuation beyond secondary school. Results reveal that, for both white and black males, DRD2 A1+ (A1A1 and A1A2 genotypes) is associated with a decreased likelihood of school continuation compared to their counterparts with DRD2 A1–; mentors who are teachers compensate for this negative association (a G × E); and youth with DRD2 A1+ are less likely to have a mentor who is a teacher than their counterparts with DRD2 A1– (a rGE).
Religious Upbringing and Neuroticism in Dutch Twin Families
Authors: Willemsen Gonneke , Boomsma Dorret I. 
Published: April 2007

AbstractEvidence for a relation between neuroticism and religion is scarce and inconsistent. The aims of the present study were to determine the association of religious upbringing with adult neuroticism scores and to examine the effect of religious upbringing on the heritability of neuroticism. As part of a longitudinal survey of twin families from the Netherlands Twin Register, data were collected on neuroticism and religious upbringing. Restricting the sample to persons aged 25 and over resulted in a sample of 4369 twins and 1304 siblings from 2698 families. Religious upbringing was significantly associated with neuroticism; in both men and women neuroticism levels were lower in those who had received a religious upbringing. There were no sex or twinsibling differences in neuroticism variances and covariances. Structural equation modeling showed differences in heritability between those with and without religious upbringing. In the group with religious upbringing, variation in neuroticism was determined for 41% by additive genetic factors and for the remaining 59% by unique environmental factors. In the group who had not received a religious upbringing, variation in neuroticism was determined for 55% by genetic factors, with evidence for both additive and nonadditive factors, and for the remaining 45% by unique environmental influences. In conclusion, having received a religious upbringing is associated with lower neuroticism scores and a lower heritability in adulthood.
Challenging a Well Established Consent Norm?: One Time Consent for Biobank Research
Authors: Caulfield Timothy , Brown Russell , Meslin Eric M 
Published: April 2007

AbstractLarge-scale biobanks of human biological materials linked to medical records are emerging as critical tools in research to tease out the complex interactions between genes and the environment and in ongoing development of diagnosis, prevention, and treatment of human disease. The evidence for this promise is found in the rush to establish these repositories by countries (Australia, UK, Sweden, Estonia, and Singapore), research organizations (NCI biobanks), and patient care groups.
Words, frequencies, and texts (particularly Conrad): A stratified approach
Authors: Moon Rosamund 
Published: April 2007

Abstract
This paper describes a corpus methodology developed in the course of investigations of three small subcorpora of texts: fiction by Conrad, nineteenth-century accounts of exploration, and adventure fiction. Stemming from observations that both high and lower frequency words in text are of interest in relation to meaning and structure, a ‘stratified approach’ integrates different levels of frequency by grouping words in a text into a series of frequency bands, identified from a reference corpus, then examining the most recurrent words within each band. This approach shows up, in particular, the ways in which topic and theme are lexicalized, and connotative lexis is associated with lower frequencies. In addition to exemplifying the approach and demonstrating its applications, the paper argues that any set of words, identified as significant through frequency, still involves selection, and that information which is derived quantitatively should not be interpreted as if wholly objective.
Disordered collarettes and uncovered tables: Negative polarity as a stylistic device in Joyce's “Two Gallants”
Authors: Nørgaard Nina 
Published: April 2007

Abstract
This article examines the use of negative polarity as a stylistic device in James Joyce's short story, “Two Gallants” (1992 [1914]). The article begins with a brief account of various approaches to negative polarity, focusing in particular on theoretical paradigms that favour the pragmatic functions of negative constructions in context. After this theoretical overview, the various approaches are applied to an analysis of Joyce's story, in the course of which it is demonstrated that although negatives are not a salient feature of the text they are nevertheless a significant meaning-making resource worth considering in analyses of literature. In particular the article aims to demonstrate how the linguistic theory of polyphony known as ScaPoLine would be a useful tool for those who wish to understand and describe the various voices that are coded by negatives and the way negative polarity is, accordingly, at times intimately connected to focalisation and narrative perspective.
Shall I compare thee? Simile understanding and semantic categories
Authors: Fishelov David 
Published: April 2007

Abstract
The purpose of this article is to present a few research findings on the process of understanding simile, where special attention was given to the semantic relationship between its three major components: Tenor (hereafter T), Vehicle (hereafter V) and Predicate (hereafter P). By manipulating different degrees of conventionality among these three components and the explicit presence of a P, eight kinds of simile emerged (e.g. conventional T and V but with unconventional P). Questionnaires were formulated consisting of lists of sixteen similes, representing the eight kinds. Subjects were asked to provide a short interpretation of the given similes, to estimate whether the simile conveyed negative, positive or neutral connotations, and finally to grade the degree of difficulty they encountered in understanding it. Thus, for example, most subjects reported that (1) “John is like a snake” says that John is a cunning and dangerous person, that it conveys negative connotations and that they had no difficulty in understanding it. Other, more “difficult” similes got diversified answers. Thus, for example, some subjects claimed that they had difficulty in understanding a phrase like (2) “John is like the state of Israel,” and responses concerning its connotations and its specific meanings were more heterogeneous. One conclusion based on the results is that subjects tend to cling to existing semantic categories not only in understanding conventional similes (and, by implication, metaphors and symbols), but also when faced with highly novel ones.
Auf dem Weg in die Zukunft: Web 2.0 in Baden-Württemberg (Facing the Future: Web 2.0 in Baden-Wuerttemberg)
Authors: Hummel Corina 
Published: April 2007

Abstract
Im August 2006 wurde das Innovationsprogramm Web 2.0 gestartet, das bis Ende 2007 aus Mitteln des Medienimpulsprogramms des Staatsministeriums Baden-Württemberg unterstützt wird. Ziel ist es, die technischen, wirtschaftlichen und sozialen Potenziale in Baden-Württemberg auszuschöpfen und die Entwicklung innovativer Projekte im Land zu forcieren. Mit einer Veranstaltungsreihe in sieben baden-württembergischen Städten informierte die MFG Baden-Württemberg in der ersten Phase über die Möglichkeiten des Web 2.0 und präsentierte erfolgreiche Beispiele. Die vier Arbeitskreise Geschäftsmodelle, Leben online, Marketing & PR und Wissensmanagement analysieren in regelmäßigen Treffen verschiedene Aspekte des Web 2.0 und treiben konkrete Projekte voran. Langfristiges Ziel des Programms ist es, durch innovative Anwendungen und Geschäftsmodelle im Bereich Web 2.0 neue Dienstleistungen und Arbeitsplätze zu schaffen.