bluuebunny/crossref_metadata_2025 huggingface dataset:
Health in Partnership: Family Nursing Practice for People With Breathing Difficulties
Authors: Jonsdottir Helga , Ingadottir Thorbjorg Soley
Published: March 2011

Reorienting the focus of health systems to incorporate a multifaceted approach that allows for comprehensive and humane health care is pending. Using the participatory paradigm approach, we describe a study of a partnership-based family nursing practice for people with breathing difficulties. We generated data through nine conversations with eight patients accompanied by a close family member ( n = 6) and one wife, 15 conversations between the authors, and through a reflective journal. Narrative data analysis was conducted. Results that reveal the meaning and experience of the family nursing practice are presented in four interlacing descriptive statements: (a) surfacing and contextualizing health problems, (b) responsiveness of services, (c) security—stability—self-direction, and (d) unified family efforts— transformation. We conclude that the conceptual framework of partnership is a useful approach to nursing practice within a nurse clinic for people with advanced breathing difficulties and their families.
Making sense of ADHD in practice: A stakeholder review
Authors: Kildea Sarah , Wright John , Davies Julie
Published: March 2011

The study aimed to explore and synthesize stakeholders’ conceptualizations and solutions concerning ADHD in the context of CAMHS. The participants were 28 stakeholders consisting of seven mental heath professionals, two teachers, seven parents/carers, five children referred for an ADHD assessment, two siblings and five peers. Individual, semi-structured interviews were held with all professionals and parents/carers. The children’s interviews used methods tailored for junior age children and were semi-structured, individual and in a group format for the peers. All interviews were transcribed verbatim and the children’s pictures were analysed. A thematic analysis was undertaken with ADHD thematically emerging as a confusing mess with conflicts reverberating across all levels of analysis from the intra-psychic world of the child to wider social contexts. Professionals attempt to make sense of this mess, parents experience the emotional impact of the mess and children’s identities are shaped by it. A reflective space where complexity, uncertainty and hidden feelings are thought about is postulated to reduce confusion and dissonance, and which in turn would enable the system to become more self aware and less naïve.
Attention-deficit hyperactivity disorder, drug companies and the internet
Authors: Mitchell Jessica , Read John
Published: March 2011

This study investigated the influence of drug-company funding on websites about attention-deficit hyperactivity disorder (ADHD). Websites in the top 60 for either Google or Yahoo!Xtra with information about causation and treatment were analysed. Likert scales, based on those used in previous similar studies, were developed to rate aetiological explanations and recommended treatment approaches, on a dimension from psycho-social to biological. Overall, the quality of information on websites was poor with a strong bias towards bio-genetic aetiological explanations of ADHD. Twenty-one of the 57 websites (37%) were funded by drug companies. The drug-company funded (DCF) websites were significantly more likely than non-DCF websites to recommend medication rather than psycho-social treatments. The selective lack of consideration of psycho-social treatments by DCF websites is discussed in relation to the relevant research literature, including the evidence in favour of a multimodal approach. The findings, which are consistent with previous similar studies in relation to websites about adult mental health problems, confirm that the pharmaceutical industry is seeking to influence public opinion via the internet.
Fracture risk assessed by Fracture Risk Assessment Tool (FRAX) compared with fracture risk derived from population fracture rates
Authors: Rubin Katrine Hass , Abrahamsen Bo , Hermann Anne Pernille , Bech Mickael , Gram Jeppe , Brixen Kim
Published: March 2011

Purpose: To evaluate the performance of the Swedish version of Fracture Risk Assessment Tool (FRAX)) without bone mass density (BMD) in a Danish population to examine the possibility of applying this version to Danish women. Methods: From the Danish National Register of social security numbers, we randomly selected 5000 women living in the region of Southern Denmark aged 40—90 years to receive a mailed questionnaire concerning risk factors for osteoporosis based on FRAX. The predicted 10-year probability of hip fractures was calculated for each woman returning a complete questionnaire using the Swedish version of FRAX. The observed 10-year hip fracture risk was also calculated for each woman using age-specific hip fracture rates from the National Hospital Discharge Register and National survival tables. Results: A total of 4194 (84%) women responded to the questionnaire and 3636 (73%) gave complete information and were included in the analysis. Using FRAX, the predicted 10-year fracture risk was 7.6%, ranging from 0.3 to 25.0% at the age of 41—50 and 81—90, respectively, while the corresponding observed fracture risk was 7.6%, ranging from 0.4 to 24.0%, respectively and not significantly different from the predicted risk (p = 0.92). Conclusions: The Swedish version of FRAX without BMD is applicable to Danish women.
Mobile phone parenting: Reconfiguring relationships between Filipina migrant mothers and their left-behind children
Authors: Madianou Mirca , Miller Daniel
Published: March 2011

The Philippines is an intensely migrant society with an annual migration of one million people, leading to over a tenth of the population working abroad. Many of these emigrants are mothers who often have children left behind. Family separation is now recognized as one of the social costs of migration affecting the global south. Relationships within such transnational families depend on long-distance communication and there is an increasing optimism among Filipino government agencies and telecommunications companies about the consequences of mobile phones for transnational families. This article draws on comparative research with UK-based Filipina migrants — mainly domestic workers and nurses — and their left-behind children in the Philippines. Our methodology allowed us to directly compare the experience of mothers and their children. The article concludes that while mothers feel empowered that the phone has allowed them to partially reconstruct their role as parents, their children are significantly more ambivalent about the consequences of transnational communication.
Breaking up ‘because of the phone’ and the transformative potential of information in Southern Mozambique
Authors: Soleil Archambault Julie
Published: March 2011

In Southern Mozambique, most people have a story about themselves or a couple they know who split up ‘because of the phone’ ( por causa do telefone). Although some stories are more dramatic than others, the kinds of misunderstandings they represent are described as the mobile’s biggest drawback. Based on research on mobile phone use among young adults in the city of Inhambane, the article focuses on instances when connections backfire and when mobile phone communication generates conflict. It examines the ways in which mobile communication participates in the circulation of and access to information: not necessarily the kind of ‘useful information’ referred to by endorsers of the ‘ICT for Development’ perspective, but rather information that is meant to remain secret. The aim is to provide an alternative perspective on the transformative potential of mobile communication in the hopes of enhancing our understanding of the impacts of the spread of the technology.
The EU Council enlarged: North-South-East or core-periphery?
Authors: Plechanovová Běla
Published: March 2011

This article aims to evaluate the emerging patterns of decision-making in the European Union after the first Eastern enlargement through an analysis of voting positions in the Council of Ministers. By applying three methods (cluster analysis, factor analysis and Bayesian item-response modelling), it assesses the new spatial dimensions of EU policy-making. The results show that the level of open contestation at the Council meetings has risen following enlargement, but the general coalition-building patterns remain similar to the ones in the old EU. The analysis also indicates that it is possible to identify a winning coalition that constitutes the critical mass of the qualified majority of weighted votes for the periods before and after the Eastern enlargement. Furthermore, the size of the largest coalition in relation to the qualified majority threshold becomes smaller in the EU of 25 member states, which may herald a new era of increased policy stability.
Vitamin B2: Riboflavin
Authors: Buehler Bruce A
Published: March 2011

Riboflavin (vitamin B 2) is not synthesized by vertebrates and must be supplied by diet. It is found in most foods, with the highest content in dairy products, meat, and dark green vegetables. Deficiency rarely occurs alone where adequate food is available and usually occurs as a multinutrient deficiency. Some conditions and medications can decrease effectiveness or levels of riboflavin. Supplementation is rarely needed to prevent ariboflavinosis when a normal diet is consumed. Supplementation for decreased frequency of migraine headaches and prevention of age related cataracts could be beneficial. There is no known toxicity.
Does Vitamin E and C Supplementation Improve the Recovery From Anterior Cruciate Ligament Surgery?
Authors: Barker Tyler , Traber Maret G.
Published: March 2011

Muscular (quadriceps) weakness is a predominant impairment that follows anterior cruciate ligament injury and surgery. This continued weakness impairs activities of daily living and could predispose patients to adverse conditions later in life, such as knee osteoarthritis. Vitamins E and C have potent antioxidant and anti-inflammatory activity. Herein, the authors summarize the state-of-the science and suggest directions for future research endeavors regarding the therapeutic influence of vitamins E and C, or other antioxidants, on the recovery from anterior cruciate ligament injury and surgery.
Seminar Review: A Review of the Basis of Surgical Treatment of Diabetic Foot Infections
Authors: Aragón-Sánchez Javier
Published: March 2011

Infection is an extremely challenging complication of foot ulcers in patients with diabetes. Surgery as part of a multidisciplinary approach is key in the management of many types of diabetic foot infections (DFIs). Unfortunately, the surgical treatment of DFIs is based more on clinical judgment and less on structured evidence, which leaves unresolved doubts. The clinical presentation of DFIs is varied. This review examines the basis of nonvascular surgical treatment of DFIs, emphasizing the importance of the anatomic concepts of the foot, the variety of its clinical presentations, and the concepts of timing surgery. Recent evidence and case reports based on the author’s experience are presented in 2 parts. The first part examines clinical presentation of infections, whereas the second part deals with imaging, foot anatomy, and some case reports.
Three Lessons Learned
Authors: Kagan Jerome
Published: March 2011

In this article, I describe varied observations from the past 60 years that motivated three significant changes in the assumptions I held as a young psychologist interested in the development of children. Aspects of these early assumptions penetrate a great deal of current research. The new beliefs are (a) a greater willingness to base concepts on patterns of measurements rather than single independent or dependent variables, (b) learning to include the physical features of the observational setting, including the procedure that generated the evidence, as well as the participants' gender, social class, and cultural background, as part of the concept, and (c) remaining aware of the possibility that the relations among continuous variables can change as a function of brain maturation during the early stages of childhood.
Statistical Trends in Women’s Participation in Science: Commentary on Valla and Ceci (2011)
Authors: Kessel Cathy , Nelson Donna J.
Published: March 2011

Valla and Ceci (2011 , this issue) describe the participation of women in science and claim that the increases in quantitative fields (e.g., mathematics, engineering, and physical sciences) are an exception to the statement that “Women’s growth in the scientific workforce has been meteoric over the past 40 years” (p. 134). We disagree and present statistics demonstrating a more positive view of the increase of the number of women in quantitative fields.
Friends and Foes of Theory Construction in Psychological Science
Authors: Garcia-Marques Leonel , Ferreira Mário B.
Published: March 2011

Newell (1973) criticized the use of vague theoretical dichotomies to account for narrowly defined empirical phenomena. Many of the problems raised by Newell persist today. We argue that these problems derive not from any peculiarity of psychological science but from the hindrances inherent to empirical theory testing. To show the contemporary relevance of these problems, we present two modern illustrations of the encumbrances faced by dichotomy-based research, we review some attempts to rely on nonempirical criteria to overcome the empirical impediments in theory testing, and we bring the question of theoretical mimicry to bear on these problems. Next, we discuss an alternative to theoretical dichotomies: the Unified Theories of Cognition (Newell, 1990). Finally, we introduce the “new experimentalism” approach in philosophy of science (Mayo, 1996), which provides a new perspective on theory construction in psychological science. We conclude with suggestions on how this new perspective can be implemented.
The Problem of Circularity in Evidence, Argument, and Explanation
Authors: Hahn Ulrike
Published: March 2011

A number of recent articles ( Fiedler, 2011 , this issue; Gigerenzer, 2009 ; Kriegeskorte, Simmons, Bellgowen, & Baker, 2009 ; Vul & Kanwisher, 2010 ) have highlighted seemingly circular arguments and explanations in psychological research, which suggests that the problem is rife within psychology. The article reviews the literature on circularity, and, in light of this, evaluates these recent examples from psychology to determine whether it is indeed circularity that is the underlying problem and to make suggestions for what paths improvements might pursue.
Received Wisdom Regarding the Roles of Craving and Dopamine in Addiction
Authors: Heyman Gene M.
Published: March 2011

Lewis's review of my book (2011, this issue) repeats widely shared understandings of the nature of addiction and the role that dopamine plays in the persistence of self-destructive drug use. These accounts depict addiction as a chronic relapsing disease and claim that drug-induced changes in dopamine function explain the transition from drug experimentation to compulsive drug use. In my book, I test the idea that addiction is a chronic, persistent state. Lewis fails to mention the results of the various tests, although they provide a handy test for his account of addiction and are surprising in light of the common verbal formula “addiction is a chronic, relapsing disease.” Consequently, I review a few of the key findings in this response. Lewis faults me for not giving enough attention to dopamine. In my book, I conclude that there is more to the biology of addiction than dopamine, and in this response, I describe research that tests the idea that drug-induced increases in dopamine markedly reduce an individual’s capacity to choose nondrug reinforcers. In one experiment, rats readily gave up cocaine for saccharin, even when they had been consuming massive amounts of the drug for weeks. Put more generally, well-established research results call for a revision of currently accepted understandings of addiction and the role that dopamine plays in drug use.
COPD: a multifactorial systemic disease
Authors: Huertas Alice , Palange Paolo
Published: March 2011

Chronic obstructive pulmonary disease (COPD) has traditionally been considered a disease of the lungs secondary to cigarette smoking and characterized by airflow obstruction due to abnormalities of both airway (bronchitis) and lung parenchyma (emphysema). It is now well known that COPD is associated with significant systemic abnormalities, such as renal and hormonal abnormalities, malnutrition, muscle wasting, osteoporosis, and anemia. However, it is still unclear whether they represent consequences of the pulmonary disorder, or whether COPD should be considered as a systemic disease. These systemic abnormalities have been attributed to an increased level of systemic inflammation. Chronic inflammation, however, may not be the only cause of the systemic effects of COPD. Recent data from humans and animal models support the view that emphysema may be a vascular disease. Other studies have highlighted the role of repair failure, bone marrow abnormality, genetic and epigenetic factors, immunological disorders and infections as potential causes of COPD systemic manifestations. Based on this new evidence, it is reasonable to consider COPD, and emphysema in particular, as ‘a disease with a significant systemic component’ if not a ‘systemic disease’ per se. The aim of this review is to give an overview of the most relevant and innovative hypothesis about the extrapulmonary manifestations of COPD.
Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair
Authors: Mithoefer Kai , Saris Daniel B.F. , Farr Jack , Kon Elizaveta , Zaslav Kenneth , Cole Brian J. , Ranstam Jonas , Yao Jian , Shive Matthew , Levine David , Dalemans Wilfried , Brittberg Mats
Published: March 2011

Objective:

To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products.

Design:

A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field.

Results:

Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved.

Conclusions:

High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project.
International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials
Authors: Hoemann Caroline , Kandel Rita , Roberts Sally , Saris Daniel B.F. , Creemers Laura , Mainil-Varlet Pierre , Méthot Stephane , Hollander Anthony P. , Buschmann Michael D.
Published: March 2011

Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.
Preclinical Studies for Cartilage Repair
Authors: Hurtig Mark B. , Buschmann Michael D. , Fortier Lisa A. , Hoemann Caroline D. , Hunziker Ernst B. , Jurvelin Jukka S. , Mainil-Varlet Pierre , McIlwraith C. Wayne , Sah Robert L. , Whiteside Robert A.
Published: March 2011

Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures.
Nonverbal Asymmetry in Interracial Interactions
Authors: Kaiser Cheryl R. , Drury Benjamin J. , Malahy Lori Wu , King Kevin M.
Published: March 2011

This study examined the role of Blacks' level of racial identification in understanding how Blacks and Whites behaved, both verbally and nonverbally, toward each other in interracial interactions. The more Blacks identified with their racial group, the more nonverbally friendly they behaved toward their White partners. Paradoxically, Whites behaved less nonverbally friendly toward Blacks who were strongly racially identified relative to those who were weakly identified. Thus, Blacks who tried the hardest in these interactions were treated the worst by Whites. Blacks' racial identification did not predict Whites' and Blacks' verbal behavior, suggesting that Whites' biases emerge only on behaviors that are difficult to control and not on behaviors that are more amenable to control.
A perspective on residual stresses in welding
Authors: De A , DebRoy T
Published: March 2011

Welding induced residual stress occurs due to non-uniform simultaneous heating and cooling, local variation in shrinkage because of variable cooling rates in different regions of the weld, and strains associated with metallurgical phase transformations. The residual stress in a welded joint can augment the externally applied load and cause structural failure. Prediction and mitigation of residual stresses still remain important issues in welding. The purpose of this special issue of Science and Technology of Welding and Joining is to present recent research on calculation, measurement and alleviation of residual stresses in welding.
Effects of thermal transport in computation of welding residual stress and distortion
Authors: Lawrence A R , Michaleris P
Published: March 2011

The effects of considering thermal transport in weld modelling of residual stress and distortion are evaluated by performing a thermal transport analysis first to compute the temperature history which is then used as loading in a conventional elastoplastic analysis to compute the residual stress. A gas metal arc welding (GMAW) and a hybrid GMAW/laser welding case are used as examples. For each weld, residual stresses are computed once assuming conductive heat transfer only and once assuming convective (thermal transport) heat transfer. For GMAW welding, both heat conduction and thermal transport analyses produced similar temperature, residual stress and distortion results, indicating that heat conduction modelling with the double ellipsoid model may be sufficient for modelling GMAW. For hybrid welding, the heat conduction and thermal transport analyses produced different temperature histories and distortion results, demonstrating the need for including thermal transport effects in modelling keyhole welding. However, the residual stress results were in close agreement, suggesting that heat conduction analyses may be sufficiently accurate for computing residual stress even in keyhole welding.
Thermometallurgical and mechanical modelling of welding – application to multipass dissimilar metal girth welds
Authors: Feulvarch E , Robin V , Bergheau J M
Published: March 2011

The prediction of welding residual stresses and distortions needs to take accurately account of the couplings between heat transfer, metallurgy and stresses–strains. The numerical simulation of multipass welding of dissimiliar metal including ferritic steels is specially difficult as three-dimensional (3D) simulation a priori needs to accurately take into account the complex phenomena in the heat affected zone and in the overlapping regions. The results obtained using a simplified two-dimensional axisymmetric model are discussed according to those resulting from a complete 3D simulation. It is shown that for multipass circular welds, 3D computations are mandatory to analyse overlapping regions but two-dimensional assumptions enable to capture stress distribution in the current region. Comparisons with experimental measurements of stresses using neutron diffraction or deep hole drilling are presented to validate the computed residual stresses.
Correction of murine β-thalassemia after minimal lentiviral gene transfer and homeostatic in vivo erythroid expansion
Authors: Negre Olivier , Fusil Floriane , Colomb Charlotte , Roth Shoshannah , Gillet-Legrand Beatrix , Henri Annie , Beuzard Yves , Bushman Frederic , Leboulch Philippe , Payen Emmanuel
Published: March 2011

A challenge for gene therapy of genetic diseases is to maintain corrected cell populations in subjects undergoing transplantation in cases in which the corrected cells do not have intrinsic selective advantage over nontransduced cells. For inherited hematopoietic disorders, limitations include inefficient transduction of stem cell pools, the requirement for toxic myelosuppression, and a lack of optimal methods for cell selection after transduction. Here, we have designed a lentiviral vector that encodes human β-globin and a truncated erythropoietin receptor, both under erythroid-specific transcriptional control. This truncated receptor confers enhanced sensitivity to erythropoietin and a benign course in human carriers. Transplantation of marrow transduced with the vector into syngenic thalassemic mice, which have elevated plasma erythropoietin levels, resulted in long-term correction of the disease even at low ratios of transduced/untransduced cells. Amplification of the red over the white blood cell lineages was self-controlled and averaged ∼ 100-fold instead of ∼ 5-fold for β-globin expression alone. There was no detectable amplification of white blood cells or alteration of hematopoietic homeostasis. Notwithstanding legitimate safety concerns in the context of randomly integrating vectors, this approach may prove especially valuable in combination with targeted integration or in situ homologous recombination/repair and may lower the required level of pretransplantation myelosuppression.
The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A
Authors: Flick Matthew J. , Chauhan Anil K. , Frederick Malinda , Talmage Kathryn E. , Kombrinck Keith W. , Miller Whitney , Mullins Eric S. , Palumbo Joseph S. , Zheng Xunzhen , Esmon Naomi L. , Esmon Charles T. , Thornton Sherry , Becker Ann , Pelc Leslie A. , Di Cera Enrico , Wagner Denisa D. , Degen Jay L.
Published: March 2011

Thrombin is a positive mediator of thrombus formation through the proteolytic activation of protease-activated receptors (PARs), fibrinogen, factor XI (fXI), and other substrates, and a negative regulator through activation of protein C, a natural anticoagulant with anti-inflammatory/cytoprotective properties. Protease-engineering studies have established that 2 active-site substitutions, W215A and E217A (fIIWE), result in dramatically reduced catalytic efficiency with procoagulant substrates while largely preserving thrombomodulin (TM)–dependent protein C activation. To explore the hypothesis that a prothrombin variant favoring antithrombotic pathways would be compatible with development but limit inflammatory processes in vivo, we generated mice carrying the fIIWE mutations within the endogenous prothrombin gene. Unlike fII-null embryos, fIIWE/WE mice uniformly developed to term. Nevertheless, these mice ultimately succumbed to spontaneous bleeding events shortly after birth. Heterozygous fIIWT/WE mice were viable and fertile despite a shift toward an antithrombotic phenotype exemplified by prolonged tail-bleeding times and times-to-occlusion after FeCl3 vessel injury. More interestingly, prothrombinWE expression significantly ameliorated the development of inflammatory joint disease in mice challenged with collagen-induced arthritis (CIA). The administration of active recombinant thrombinWE also suppressed the development of CIA in wild-type mice. These studies provide a proof-of-principle that pro/thrombin variants engineered with altered substrate specificity may offer therapeutic opportunities for limiting inflammatory disease processes.
Limited stage I disease is not necessarily indicative of an excellent prognosis in childhood anaplastic large cell lymphoma
Authors: Attarbaschi Andishe , Mann Georg , Rosolen Angelo , Williams Denise , Uyttebroeck Anne , Marky Ildiko , Lamant Laurence , Horibe Keizo , Wrobel Grazyna , Beishuizen Auke , Wössmann Wilhelm , Reiter Alfred , Mauguen Audrey , Le Deley Marie-Cecile , Brugières Laurence ,   for the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) ALCL99 Trial
Published: March 2011

Data on incidence, characteristics, and prognosis in stage I childhood anaplastic large cell lymphoma are scarce. Of 463 patients enrolled in the international ALCL99 trial, 36 (8%) had stage I disease and were treated with a prephase chemotherapy, followed by either 3 chemotherapy courses in case of initial complete resection (6 patients) or otherwise by 6 courses of chemotherapy (30 patients). Disease localization was to the peripheral lymph nodes in 26, soft tissue mass in 8, and solitary bone and bronchial disease in 1 patient each. Of the 6 patients with complete resection, none experienced relapse, whereas of the 30 remaining stage I patients, 9 (30%) relapsed, including in all cases a new site of disease involvement and including 3 of 5 anaplastic lymphoma kinase–negative patients. In summary, the failure rate for incompletely resected stage I disease was similar to that for patients with stage II and stage III/IV disease. Whether anaplastic lymphoma kinase negativity contributed to this moderate outcome has to be proven prospectively. This study was registered at www.clinicaltrials.gov as NCT00006455.
Overexpression of the UGT73C6 alters brassinosteroid glucoside formation in Arabidopsis thaliana
Authors: Husar Sigrid , Berthiller Franz , Fujioka Shozo , Rozhon Wilfried , Khan Mamoona , Kalaivanan Florian , Elias Luisa , Higgins Gillian S , Li Yi , Schuhmacher Rainer , Krska Rudolf , Seto Hideharu , Vaistij Fabian E , Bowles Dianna , Poppenberger Brigitte
Published: March 2011

Background

Brassinosteroids (BRs) are signaling molecules that play essential roles in the spatial regulation of plant growth and development. In contrast to other plant hormones BRs act locally, close to the sites of their synthesis, and thus homeostatic mechanisms must operate at the cellular level to equilibrate BR concentrations. Whilst it is recognized that levels of bioactive BRs are likely adjusted by controlling the relative rates of biosynthesis and by catabolism, few factors, which participate in these regulatory events, have as yet been identified. Previously we have shown that the UDP-glycosyltransferase UGT73C5 of Arabidopsis thaliana catalyzes 23-O-glucosylation of BRs and that glucosylation renders BRs inactive. This study identifies the closest homologue of UGT73C5, UGT73C6, as an enzyme that is also able to glucosylate BRs in planta.

Results

In a candidate gene approach, in which homologues of UGT73C5 were screened for their potential to induce BR deficiency when over-expressed in plants, UGT73C6 was identified as an enzyme that can glucosylate the BRs CS and BL at their 23-O-positions in planta. GUS reporter analysis indicates that UGT73C6 shows over-lapping, but also distinct expression patterns with UGT73C5 and YFP reporter data suggests that at the cellular level, both UGTs localize to the cytoplasm and to the nucleus. A liquid chromatography high-resolution mass spectrometry method for BR metabolite analysis was developed and applied to determine the kinetics of formation and the catabolic fate of BR-23-O-glucosides in wild type and UGT73C5 and UGT73C6 over-expression lines. This approach identified novel BR catabolites, which are considered to be BR-malonylglucosides, and provided first evidence indicating that glucosylation protects BRs from cellular removal. The physiological significance of BR glucosylation, and the possible role of UGT73C6 as a regulatory factor in this process are discussed in light of the results presented.

Conclusion

The present study generates essential knowledge and molecular and biochemical tools, that will allow for the verification of a potential physiological role of UGT73C6 in BR glucosylation and will facilitate the investigation of the functional significance of BR glucoside formation in plants.
Enhancement of heat transfer and entropy generation analysis of nanofluids turbulent convection flow in square section tubes
Authors: Bianco Vincenzo , Nardini Sergio , Manca Oronzio
Published: March 2011

In this article, developing turbulent forced convection flow of a water-Al2O3 nanofluid in a square tube, subjected to constant and uniform wall heat flux, is numerically investigated. The mixture model is employed to simulate the nanofluid flow and the investigation is accomplished for particles size equal to 38 nm.

An entropy generation analysis is also proposed in order to find the optimal working condition for the given geometry under given boundary conditions. A simple analytical procedure is proposed to evaluate the entropy generation and its results are compared with the numerical calculations, showing a very good agreement.

A comparison of the resulting Nusselt numbers with experimental correlations available in literature is accomplished. To minimize entropy generation, the optimal Reynolds number is determined.
Efficient nonlinear Bayesian survey design usingDNoptimization
Authors: Coles Darrell , Curtis Andrew
Published: March 2011

A new method for fully nonlinear, Bayesian survey design renders the optimization of industrial-scale geoscientific surveys as a practical possibility. The method, DNoptimization, designs surveys to maximally discriminate between different possible models. It is based on a generalization to nonlinear design problems of the D criterion (which is for linearized design problems). The main practical advantage of DNoptimization is that it uses efficient algorithms developed originally for linearized design theory, resulting in lower computing and storage costs than for other nonlinear Bayesian design techniques. In a real example in which we optimized a seafloor microseismic sensor network to monitor a fractured petroleum reservoir, we compared DNoptimization with two other networks: one proposed by an industrial contractor and one optimized using a linearized Bayesian design method. Our technique yielded a network with superior expected data quality in terms of reduced uncertainties on hypocenter locations.
Aberrant Expression of Thyroid Hormone Receptor β Isoform May Cause Inappropriate Secretion of TSH in a TSH-Secreting Pituitary Adenoma
Authors: Tagami Tetsuya , Usui Takeshi , Shimatsu Akira , Beniko Mutsuo , Yamamoto Hiroyuki , Moriyama Kenji , Naruse Mitsuhide
Published: March 2011

Context:

Patients with TSH-secreting pituitary adenomas (TSHoma) show inappropriate secretion of TSH; serum TSH levels are not suppressed despite high serum free thyroid hormone levels. The mechanism of a defect in negative regulation of TSH in a TSHoma is still unclear.

Objective:

Recently, we cloned a novel thyroid hormone receptor β isoform (TRβ4) from a human pituitary library. To elucidate the clinical significance of TRβ4, we investigated the expression of this isoform in TSHoma.

Methods:

RT-PCR was performed to detect TRβ isoforms such as TRβ1, TRβ2, and TRβ4 using RNA obtained from surgically resected TSHoma. The effects of TRβ4 on the TSH gene expression were examined in the transient gene expression experiments.

Results:

Quantitative analysis using a real-time PCR revealed that relative expression of TRβ4 to TRβ1+2 was higher in three TSHoma than in a prolactinoma or a nonfunctioning pituitary adenoma. TRβ4 construct did not mediate T3-dependent gene regulation but inhibited the negative regulation of TSHα mediated by TRβ1 or TRβ2.

Conclusions:

Aberrant expression of TRβ4 may partly contribute to the inappropriate secretion of TSH in a TSHoma.
Teriparatide, Vitamin D, and Calcium Healed Bilateral Subtrochanteric Stress Fractures in a Postmenopausal Woman with a 13-Year History of Continuous Alendronate Therapy
Authors: Gomberg Stephen J. , Wustrack Rosanna L. , Napoli Nicola , Arnaud Claude D. , Black Dennis M.
Published: March 2011

Background:

Oral bisphosphonates comprise the most widely prescribed class of antiosteoporotic drugs. Recent reports, however, propose a link between prolonged bisphosphonate use and atypical, low-energy, subtrochanteric fractures.

Objectives:

The aim was to describe the clinical course of a patient treated long-term with alendronate who developed subtrochanteric stress fractures and to propose a hypothesis to explain teriparatide's potential contribution in healing the patient's stress fractures.

Results:

Magnetic resonance imaging (MRI) showed classical bilateral stress fractures of the mid-femora. Baseline serum 25-hydroxyvitamin D3 was low; bone-specific alkaline phosphatase was slightly increased; serum carboxyterminal cross-linking telopeptide of bone collagen and urine aminoterminal cross-linking telopeptide of bone collagen were low to normal, as was serum osteocalcin. Dual-energy x-ray absorptiometry showed osteopenic vertebral bone mineral density and osteoporotic hip values. Treatment with large doses of oral vitamin D increased serum 25-hydroxyvitamin D3 to normal within 2 months, after which it remained in the normal range with maintenance doses. Thigh pain, present as an initial symptom, intensified, and the MRI appearance of the fractures worsened. Teriparatide treatment commenced, and 6 months later, a repeat MRI showed decreased edema at the fracture sites with faint cortical bridging. Thigh pain and lower limb weakness disappeared over the next year, and complete fracture healing was established (MRI).

Conclusions:

Based upon the chronology of fracture healing in our patient and published evidence that teriparatide heals stress fractures in a rat model, we think that teriparatide was probably primary in this patient's positive response to therapy, with calcium, vitamin D therapy, and alendronate discontinuation playing secondary roles.
Life without Empire: Audiencia Ministers after Independence
Authors: Burkholder Mark A.
Published: March 2011

“Life without Empire: Audiencia Ministers after Independence” draws upon sources from Spain’s national, regional, and university archives to examine men with audiencia positions in Spain and in the Indies from the end of the sale of appointments in 1750 to 1821. In 1750 these ministers shared backgrounds of gender and university study of civil law, canon law, or both. They differed in regard to place of birth, the purchase of an initial audiencia appointment, age at first appointment, educational experience and university affiliation, prior government service and university teaching, and the extent of prominent letrado relatives serving audiencias, chancellories, and councils. By 1808 these differences had largely disappeared and a much more homogenous corps of ministers served on the tribunals. The changes in background facilitated the incorporation into the Spanish courts of a substantial number of ministers with American service after independence. Many creole and the few peninsular ministers who remained in the Americas after independence also obtained positions there. Compared to intendants and bishops in the Americas, ministers on New World audiencias proved relatively successful in securing posts after independence. In terms of subsequent offices held, the handful of creole audiencia ministers that emigrated to Spain fared better than the peninsulars that remained in the newly independent states.
IGF signaling directs ventricular cardiomyocyte proliferation during embryonic heart development
Authors: Li Peng , Cavallero Susana , Gu Ying , Chen Tim H. P. , Hughes Jennifer , Hassan A. Bassim , Brüning Jens C. , Pashmforoush Mohammad , Sucov Henry M.
Published: March 2011

Secreted factors from the epicardium are believed to be important in directing heart ventricular cardiomyocyte proliferation and morphogenesis, although the specific factors involved have not been identified or characterized adequately. We found that IGF2 is the most prominent mitogen made by primary mouse embryonic epicardial cells and by a newly derived immortalized mouse embryonic epicardial cell line called MEC1. In vivo, Igf2 is expressed in the embryonic mouse epicardium during midgestation heart development. Using a whole embryo culture assay in the presence of inhibitors, we confirmed that IGF signaling is required to activate the ERK proliferation pathway in the developing heart, and that the epicardium is required for this response. Global disruption of the Igf2 gene, or conditional disruption of the two IGF receptor genes Igf1r and Insr together in the myocardium, each resulted in a significant decrease in ventricular wall proliferation and in ventricular wall hypoplasia. Ventricular cardiomyocyte proliferation in mutant embryos was restored to normal at E14.5, concurrent with the establishment of coronary circulation. Our results define IGF2 as a previously unexplored epicardial mitogen that is required for normal ventricular chamber development.
Assembly and patterning of the vascular network of the vertebrate hindbrain
Authors: Fujita Misato , Cha Young R. , Pham Van N. , Sakurai Atsuko , Roman Beth L. , Gutkind J. Silvio , Weinstein Brant M.
Published: March 2011

The cranial vasculature is essential for the survival and development of the central nervous system and is important in stroke and other brain pathologies. Cranial vessels form in a reproducible and evolutionarily conserved manner, but the process by which these vessels assemble and acquire their stereotypic patterning remains unclear. Here, we examine the stepwise assembly and patterning of the vascular network of the zebrafish hindbrain. The major artery supplying the hindbrain, the basilar artery, runs along the ventral keel of the hindbrain in all vertebrates. We show that this artery forms by a novel process of medial sprouting and migration of endothelial cells from a bilateral pair of primitive veins, the primordial hindbrain channels. Subsequently, a second wave of dorsal sprouting from the primordial hindbrain channels gives rise to angiogenic central arteries that penetrate into and innervate the hindbrain. The chemokine receptor cxcr4a is expressed in migrating endothelial cells of the primordial hindbrain channels, whereas its ligand cxcl12b is expressed in the hindbrain neural keel immediately adjacent to the assembling basilar artery. Knockdown of either cxcl12b or cxcr4a results in defects in basilar artery formation, showing that the assembly and patterning of this crucial artery depends on chemokine signaling.
Mitophagy in yeast is independent of mitochondrial fission and requires the stress response gene WHI2
Authors: Mendl Nadine , Occhipinti Angelo , Müller Matthias , Wild Philipp , Dikic Ivan , Reichert Andreas S.
Published: March 2011

Dysfunctional mitochondria show a reduced capacity for fusion and, as mitochondrial fission is maintained, become spatially separated from the intact network. By that mechanism, dysfunctional mitochondria have been proposed to be targeted for selective degradation by mitophagy, thereby providing a quality control system for mitochondria. In yeast, conflicting results concerning the role of mitochondrial dynamics in mitophagy have been reported. Here, we investigate the effects on mitophagy of altering mitochondrial fission and fusion, using biochemical, as well as fluorescence-based, assays. Rapamycin-induced mitophagy was shown to depend upon the autophagy-related proteins Atg11, Atg20 and Atg24, confirming that a selective type of autophagy occurred. Both fragmentation of mitochondria and inhibition of oxidative phosphorylation were not sufficient to trigger mitophagy, and neither deletion of the fission factors Dnm1, Fis1, Mdv1 or Caf4 nor expression of dominant-negative variants of Dnm1 impaired mitophagy. The diminished mitophagy initially observed in a Δfis1 mutant was not due to the absence of Fis1 but rather due to a secondary mutation in WHI2, which encodes a factor reported to function in the general stress response and the Ras-protein kinase A (PKA) signaling pathway. We propose that, in yeast, mitochondrial fission is not a prerequisite for the selective degradation of mitochondria, and that mitophagy is linked to the general stress response and the Ras-PKA signaling pathway.