bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between serious injury and blood alcohol concentration (BAC) in fatal motor vehicle accidents: BAC = 0.01% is associated with significantly more dangerous accidents than BAC = 0.00%
Authors: Phillips David P. , Brewer Kimberly M.
Published: June 2011

Aim  To analyze the severity of automotive injuries associated with blood alcohol concentration (BAC) in increments of 0.01%.

Design/setting  Epidemiological study using the Fatality Analysis Reporting System.

Participants  All people in US fatal automotive accidents, 1994–2008 (n = 1 495 667).

Measurements  The ratio of serious: non‐serious injuries for drivers, by BAC.

Findings  Accident severity increases significantly even when the driver is merely ‘buzzed’, a finding that persists after standardization for various confounding factors. Three mechanisms mediate between buzzed driving and high accident severity: compared to sober drivers, buzzed drivers are significantly more likely to speed, to be improperly seatbelted and to drive the striking vehicle. In addition, there is a strong ‘dose–response’ relationship for all three factors in relation to accident severity (e.g. the greater the BAC, the greater the average speed of the driver and the greater the severity of the accident).

Conclusions  The severity of life‐threatening motor vehicle accidents increases significantly at blood alcohol concentrations (BACs) far lower than the current US limit of 0.08%. Lowering the legal limit could save lives, prevent serious injuries and reduce financial and social costs associated with motor vehicle accidents.
Factor X deficiency and intracranial bleeding: who is at risk?
Authors: RAUCH R. , GIRISCH M. , WIEGAND G. , SCHROEDER W. , HOFBECK M. , WELISCH E. , WULFF K.
Published: June 2011

Summary.  Very few mutations of the gene encoding for coagulation factor X (FX) have been found associated with intracranial haemorrhage (ICH) due to FX deficiency (FXD). No guidelines exist as to when prophylaxis in FXD should be started and how patients at risk for ICH can be identified. We report on a novel mutation causative for ICH in a family of Iranian origin and provide a summary of all published mutations in the FX gene related to ICH. The index patient is an infant with umbilical bleeding requiring blood transfusion in the postnatal period. The international normalized ratio (6.01) and activated partial thromboplastin time (117 s) were prolonged. Coagulation factor analysis was normal except for FX activity (<1%). At 4 months, the child suffered a spontaneous severe intracranial haemorrhage. The child was the product of a consanguineous union. Four of five available family members from three generations displayed minor bleeding symptoms and mildly reduced FX. Sequencing of FX gene demonstrated homozygosity for a novel duplication A (c.1402_1403dupA)* in exon 8 and heterozygosity in four family members. We compare this case to all 15 patients with FXD and ICH and their 11 known mutations described so far. This case illustrates a pattern of FXD (a male neonate with umbilical or gastrointestinal bleeding, very low FX:C (<1%) and an underlying homozygous genotype) who may be at high risk for ICH. In these cases, we recommend to start early prophylactic substitution of FX to prevent a possible life‐threatening haemorrhage.
Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence
Authors: ARANDA MANUEL , BANASZAK ANASTAZIA T. , BAYER TILL , LUYTEN JAMES R. , MEDINA MÓNICA , VOOLSTRA CHRISTIAN R.
Published: June 2011

Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high‐density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca2+ homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis‐related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.
Corporate social responsibility as cultural meaning management: a critique of the marketing of ‘ethical’ bottled water
Authors: Brei Vinicius , Böhm Steffen
Published: June 2011

To date, the primary focus of research in the field of corporate social responsibility (CSR) has been on the strategic implications of CSR for corporations and less on an evaluation of CSR from a wider political, economic and social perspective. In this paper, we aim to address this gap by critically engaging with marketing campaigns of so‐called ‘ethical’ bottled water. We especially focus on a major CSR strategy of a range of different companies that promise to provide drinking water for (what they name as) ‘poor African people’ by way of Western consumers purchasing bottled water. Following Fairclough's approach, we unfold a three‐step critical discourse analysis of the marketing campaigns of 10 such ‘ethical’ brands. Our results show that bottled water companies try to influence consumers' tastes through the management of the cultural meaning of bottled water, producing a more ‘ethical’ and ‘socially responsible’ perception of their products/brands. Theoretically, we base our analysis on McCracken's model of the cultural meaning of consumer goods, which, we argue, offers a critical perspective of the recent emergence of CSR and business ethics initiatives. We discuss how these marketing campaigns can be framed as historical struggles associated with neo‐liberal ideology and hegemony. Our analysis demonstrates how such CSR strategies are part of a general process of the reproduction of capitalist modes of accumulation and legitimation through the usage of cultural categories.
The moral significance of gestures
Authors: ten Bos René
Published: June 2011

The concept of the gesture is explored in relationship with its moral significance rather than, for example, its aesthetic significance. It is argued that the concept can be used in order to make clear how morality relates to the body. This is not to suggest that gestures can be neatly defined. On the contrary, they always seem to be ambivalent and somewhat nebular. However, it will be shown that some of their significance might well be related to popular concepts such as ‘transparency’, ‘authenticity’, ‘integrity’ and ‘responsibility’. In order to make this clear, the role of some particular gestures in politics and organizational life, most notably ‘apology’ and ‘trust’, will be discussed throughout the paper.
Curcumin prevents corticosterone‐induced neurotoxicity and abnormalities of neuroplasticity via 5‐HT receptor pathway
Authors: Xu Ying , Li Shan , Vernon Matthew M. , Pan Jianchun , Chen Ling , Barish Philip A. , Zhang Yuan , Acharya Abhinav P. , Yu Jie , Govindarajan Subramaniam S. , Boykin Erin , Pan Xiaoyu , O’Donnell James M. , Ogle William O.
Published: June 2011

J. Neurochem. (2011) 118, 784–795.

Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5‐hydroxy tryptamine (5‐HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5‐HT receptor subtypes, 5‐HT1A, 5‐HT2A and 5‐HT4, but 5‐HT1B, 5‐HT2B, 5‐HT2C, 5‐HT6 and 5‐HT7 receptors remain unchanged. Pre‐treatment with curcumin reversed this effect on mRNA for the 5‐HT1A and 5‐HT4 receptors, but not for the 5‐HT2A receptor. Moreover, curcumin exerted a neuroprotective effect against corticosterone‐induced neuronal death. This observed effect of curcumin was partially blocked by either 5‐HT1A receptor antagonist p‐MPPI or 5‐HT4 receptor antagonist RS 39604 alone; whereas, the simultaneous application of both antagonists completely reversed the effect. Curcumin was also found to regulate corticosterone‐induced morphological changes such as increases in soma size, dendritic branching and dendritic spine density, as well as elevate synaptophysin expression in cortical neurons. p‐MPPI and RS 39604 reversed the effect of curcumin‐induced change in neuronal morphology and synaptophysin expression of corticosterone‐treated neurons. In addition, an increase in cyclic adenosine monophosphate (cAMP) level was observed after curcumin treatment, which was further prevented by RS 39604, but not by p‐MPPI. However, curcumin‐induced elevation in protein kinase A activity and phosphorylation of cAMP response element‐binding protein levels were inhibited by both p‐MPPI and RS 39604. These findings suggest that the neuroprotection and modulation of neuroplasticity exhibited by curcumin might be mediated, at least in part, via the 5‐HT receptor‐cAMP‐PKA‐CREB signal pathway.
Improvements in the visual evaluation of soil structure
Authors: Guimarães R. M. L. , Ball B. C. , Tormena C. A.
Published: June 2011

Spade methods to visually evaluate soil structural quality (Sq) are simple, quick, cheap and can be used by farmers, gardeners, consultants and the scientific community. However, European and Brazilian users of one such method, viz. visual evaluation of soil structure (VESS) which is a development of the Peerlkamp test, have been concerned about its subjectivity. The method of soil slice break‐up and operator influence on scores have been questioned. Thus, our aim was to make soil scoring by the VESS technique more objective and thus to revise the scoring guide. We compared scoring with normal breaking up of the soil slice by hand with scoring after breaking up the slice by dropping (drop shatter) to make the soil break‐up more operator independent. After slice break‐up, aggregates were split by hand and their internal porosity was evaluated to develop the use of visible porosity as an aid to scoring. This proved inconclusive on its own, so a method of reducing larger aggregates to 1.5–2.0 cm core fragments and describing their shape and porosity was developed to score soil Sq. Breaking up a spadeful of soil by hand or by dropping resulted in the same Sq score. The method of reducing aggregates and evaluation of their shape improved VESS, particularly in the middle range of soil quality and the revised chart is shown. VESS was sensitive to changes in Sq in layers within the profile and its use for diagnosing Sq in different layers allows targeted soil improvement by tillage.
Vascular Incompetence in Dialysis Patients—Protein‐Bound Uremic Toxins and Endothelial Dysfunction
Authors: Jourde‐Chiche Noémie , Dou Laetitia , Cerini Claire , Dignat‐George Françoise , Brunet Philippe
Published: June 2011

Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium‐dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia‐specific factors. Several uremic toxins, mostly protein‐bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p‐cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro‐oxidant and pro‐inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein‐bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.
Promoting Behavior Change from Alcohol Use Through Mobile Technology: The Future of Ecological Momentary Assessment
Authors: Cohn Amy M. , Hunter‐Reel Dorian , Hagman Brett T. , Mitchell Jessica
Published: June 2011

Background:  Interactive and mobile technologies (i.e., smartphones such as Blackberries, iPhones, and palm‐top computers) show promise as an efficacious and cost‐effective means of communicating health‐behavior risks, improving public health outcomes, and accelerating behavior change. The present study was conducted as a “needs assessment” to examine the current available mobile smartphone applications (e.g., apps) that utilize principles of ecological momentary assessment (EMA)—daily self‐monitoring or near real‐time self‐assessment of alcohol‐use behavior—to promote positive behavior change, alcohol harm reduction, psycho‐education about alcohol use, or abstinence from alcohol.

Methods:  Data were collected and analyzed from iTunes for Apple iPhone©. An inventory assessed the number of available apps that directly addressed alcohol use and consumption, alcohol treatment, or recovery, and whether these apps incorporated empirically based components of alcohol treatment.

Results:  Findings showed that few apps addressed alcohol‐use behavior change or recovery. Aside from tracking drinking consumption, a minority utilized empirically based components of alcohol treatment. Some apps claimed they could serve as an intervention; however, no empirical evidence was provided.

Conclusions:  More studies are needed to examine the efficacy of mobile technology in alcohol intervention studies. The large gap between availability of mobile apps and their use in alcohol treatment programs indicates several important future directions for research.
The Protective Action Decision Model: Theoretical Modifications and Additional Evidence
Authors: Lindell Michael K. , Perry Ronald W.
Published: June 2011

The Protective Action Decision Model (PADM) is a multistage model that is based on findings from research on people's responses to environmental hazards and disasters. The PADM integrates the processing of information derived from social and environmental cues with messages that social sources transmit through communication channels to those at risk. The PADM identifies three critical predecision processes (reception, attention, and comprehension of warnings or exposure, attention, and interpretation of environmental/social cues)—that precede all further processing. The revised model identifies three core perceptions—threat perceptions, protective action perceptions, and stakeholder perceptions—that form the basis for decisions about how to respond to an imminent or long‐term threat. The outcome of the protective action decision‐making process, together with situational facilitators and impediments, produces a behavioral response. In addition to describing the revised model and the research on which it is based, this article describes three applications (development of risk communication programs, evacuation modeling, and adoption of long‐term hazard adjustments) and identifies some of the research needed to address unresolved issues.
The Separation Plot: A New Visual Method for Evaluating the Fit of Binary Models
Authors: Greenhill Brian , Ward Michael D. , Sacks Audrey
Published: June 2011

We present a visual method for assessing the predictive power of models with binary outcomes. This technique allows the analyst to evaluate model fit based upon the models’ ability to consistently match high‐probability predictions to actual occurrences of the event of interest, and low‐probability predictions to nonoccurrences of the event of interest. Unlike existing methods for assessing predictive power for logit and probit models such as Percent Correctly Predicted statistics, Brier scores, and the ROC plot, our “separation plot” has the advantage of producing a visual display that is informative and easy to explain to a general audience, while also remaining insensitive to the often arbitrary probability thresholds that are used to distinguish between predicted events and nonevents. We demonstrate the effectiveness of this technique in building predictive models in a number of different areas of political research.
Certification of a Boron Carbide Powder Reference Material for Chemical Analysis
Authors: Matschat Ralf , Dette Angelika , Richter Silke , Recknagel Sebastian , Barth Peter
Published: June 2011

The certification of a boron carbide reference material for chemical composition is described. The mass fractions of 16 elements and two boron species are certified in an international interlaboratory comparison with 35 participating laboratories from six different countries. Beside chemical characterization the certification process includes homogeneity and stability testing of the candidate material boron carbide (type F360, 305M422). Details of the analytical methods used for chemical characterization and of the calculation of the uncertainties of the certified mass fractions are given. The new reference material ERM®‐ED102 with certified mass fractions of 18 parameters (elements and species) and of the amount fraction of the isotope 10B is a valuable tool for laboratories working in the field of advanced ceramic materials analysis to improve their analytical results.
Pathophysiology of allergic inflammation
Authors: Barnes Peter J.
Published: June 2011

Summary:  Allergic inflammation is due to a complex interplay between several inflammatory cells, including mast cells, basophils, lymphocytes, dendritic cells, eosinophils, and sometimes neutrophils. These cells produce multiple inflammatory mediators, including lipids, purines, cytokines, chemokines, and reactive oxygen species. Allergic inflammation affects target cells, such as epithelial cells, fibroblasts, vascular cells, and airway smooth muscle cells, which become an important source of inflammatory mediators. Sensory nerves are sensitized and activated during allergic inflammation and produce symptoms. Allergic inflammatory responses are orchestrated by several transcription factors, particularly NF‐κB and GATA3. Inflammatory genes are also regulated by epigenetic mechanisms, including DNA methylation and histone modifications. There are several endogenous anti‐inflammatory mechanisms, including anti‐inflammatory lipids and cytokines, which may be defective in allergic disease, thus amplifying and perpetuating the inflammation. Better understanding of the pathophysiology of allergic inflammation has identified new therapeutic targets but developing effective novel therapies has been challenging. Corticosteroids are highly effective with a broad spectrum of anti‐inflammatory effects, including epigenetic modulation of the inflammatory response and suppression of GATA3.
Allergens and their role in the allergic immune response
Authors: Platts‐Mills Thomas A. E. , Woodfolk Judith A.
Published: June 2011

Summary:  Allergens are recognized as the proteins that induce immunoglobulin E (IgE) responses in humans. The proteins come from a range of sources and, not surprisingly, have many different biological functions. However, the delivery of allergens to the nose is exclusively on particles, which carry a range of molecules in addition to the protein allergens. These molecules include pathogen‐associated molecular patterns (PAMPs) that can alter the response. Although the response to allergens is characterized by IgE antibodies, it also includes other isotypes (IgG, IgA, and IgG4), as well as T cells. The challenge is to identify the characteristics of these exposures that favor the production of this form of response. The primary features of the exposure appear to be the delivery in particles, such as pollen grains or mite feces, containing both proteins and PAMPs, but with overall low dose. Within this model, there is a simple direct relationship between the dose of exposure to mite or grass pollen and the prevalence of IgE responses. By contrast, the highest levels of exposure to cat allergen are associated with a lower prevalence of IgE responses. Although the detailed mechanisms for this phenomenon are not clear, it appears that enhanced production of interleukin‐10 in response to specific Fel d 1 peptides could influence the response. However, it is striking that the animal sources that are most clearly associated with decreased responses at high allergen dose are derived from animals from which humans evolved more recently (∼65 million years ago). Although the nose is still recognized as the primary route for sensitization to inhalant allergens, there is increasing evidence that the skin is also an important site for the generation of IgE antibody responses. By contrast, it is now evident that delivery of foreign proteins by the oral route or sublingually will favor the generation of tolerance.
Atopic dermatitis: a disease of altered skin barrier and immune dysregulation
Authors: Boguniewicz Mark , Leung Donald Y. M.
Published: June 2011

Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.
Imaging Single Endocytic Events Reveals Diversity in Clathrin, Dynamin and Vesicle Dynamics
Authors: Mattheyses Alexa L. , Atkinson Claire E. , Simon Sanford M.
Published: June 2011

The dynamics of clathrin‐mediated endocytosis can be assayed using fluorescently tagged proteins and total internal reflection fluorescence microscopy. Many of these proteins, including clathrin and dynamin, are soluble and changes in fluorescence intensity can be attributed either to membrane/vesicle movement or to changes in the numbers of individual molecules. It is important for assays to discriminate between physical membrane events and the dynamics of molecules. Two physical events in endocytosis were investigated: vesicle scission from the plasma membrane and vesicle internalization. Single vesicle analysis allowed the characterization of dynamin and clathrin dynamics relative to scission and internalization. We show that vesicles remain proximal to the plasma membrane for variable amounts of time following scission, and that uncoating of clathrin can occur before or after vesicle internalization. The dynamics of dynamin also vary with respect to scission. Results from assays based on physical events suggest that disappearance of fluorescence from the evanescent field should be re‐evaluated as an assay for endocytosis. These results illustrate the heterogeneity of behaviors of endocytic vesicles and the importance of establishing suitable evaluation criteria for biophysical processes.
DOES NEUROSCIENCE MATTER FOR EDUCATION?
Authors: Schrag Francis
Published: June 2011

In this review essay, Francis Schrag focuses on two recent anthologies dealing completely or in part with the role of neuroscience in learning and education: The Jossey‐Bass Reader on the Brain and Learning, edited by Jossey‐Bass Publishers, and New Philosophies of Learning, edited by Ruth Cigman and Andrew Davis. Schrag argues that philosophers of education do have a distinctive role in the conversation about neuroscience. He contends that the impact of neuroscience is likely to be substantial, though not in the way its advocates imagine. It has the potential to enhance education by way of interventions that successfully alter the fundamental neural mechanisms of learning, but neuroscience is unlikely to affect classroom teaching substantially.
Comparison of the Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil vs Valsartan by Ambulatory Blood Pressure Monitoring
Authors: Sica Domenic , White William B. , Weber Michael A. , Bakris George L. , Perez Alfonso , Cao Charlie , Handley Alison , Kupfer Stuart
Published: June 2011

J Clin Hypertens (Greenwich). 2011;13:467–472. ©2011 Wiley Periodicals, Inc.

Azilsartan medoxomil (AZL‐M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL‐M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double‐blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24‐hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL‐M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24‐hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL‐M 40 mg and 80 mg lowered 24‐hour mean systolic BP (−14.9 mm Hg and −15.3 mm Hg, respectively) more than VAL 320 mg (−11.3 mm Hg; P<.001 for 40‐mg and 80‐mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (−14.9 mm Hg for AZL‐M 40 mg and −16.9 mm Hg for AZL‐M 80 mg vs −11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24‐hour mean and clinic diastolic BPs were also greater with both doses of AZL‐M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL‐M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL‐M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL‐M could provide higher rates of hypertension control compared with other ARBs in the class.
ARIES‐3: Ambrisentan Therapy in a Diverse Population of Patients with Pulmonary Hypertension
Authors: Badesch David B. , Feldman Jeremy , Keogh Anne , Mathier Michael A. , Oudiz Ronald J. , Shapiro Shelley , Farber Harrison W. , McGoon Michael , Frost Adaani , Allard Martine , Despain Darrin , Dufton Christopher , Rubin Lewis J. ,   for the ARIES‐3 Study Group
Published: June 2011

Introduction: Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies. Aims: ARIES‐3 was an open‐label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6‐minute walk distance (6MWD) at week 24. Results: A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 12–29) and a decrease in B‐type natriuretic peptide (–26%; 95% CI: –34 to –16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non‐Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events. Conclusion: This study reconfirms the results of previous placebo‐controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non‐Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations.
Adjustment and coping in adults with sickle cell disease: An assessment of research evidence
Authors: Midence Kenny , Elander James
Published: June 2011

This paper considers the findings from psychological studies of adults with sickle cell disease (SCD), an inherited haematological disorder which causes recurrent episodes of acute pain. Studies are reviewed that deal with aspects of the condition's clinical presentation in adulthood, the risk of maladjustment and psychopathology among affected groups, the role played by cognitive factors in mediating psychological distress and facilitating more effective coping, and the implications of the condition for family life and employment. Adults with SCD experience high levels of maladjustment by comparison with other illness groups, and differences in adjustment are predicted better by measures of social support and life stress than by illness variables. The use of coping strategies plays an important role in pain management and the mediation of psychosocial adjustment, with passive and negative responses to painful episodes associated with less favourable outcomes. Existing findings in this rapidly expanding area of research have implications for the management of SCD and the organization of support services, and point to a need for interventions to enhance patients' coping skills. Future research could evaluate specific cognitive and behavioural interventions to promote more effective coping, and look at the effects of SCD on reproductive behaviour, family life, performance in the workplace, and development and adjustment over the life‐span.
Clinical‐ versus home‐based treatment formats for children with chronic headache
Authors: Griffiths Jennifer D. , Martin Paul R.
Published: June 2011

This study evaluated the effectiveness of a cognitive–behavioural treatment programme, delivered in either clinic‐based group format, or home‐based minimal‐therapist‐contact format, in the treatment of chronic headache (migraine, tension or combined), for 10–12‐year‐old children. Subjects were assigned randomly to three conditions: clinic‐based treatment (eight sessions); home‐based treatment (three sessions supplemented by working at home from treatment manuals); and waiting‐list control. Both treatment conditions were associated with significant reductions in headaches, but no changes occurred for the control condition. The two treatment formats were equally efficacious; however, the home‐based format was over twice as cost effective as the clinic‐based format.
Pain and helplessness as correlates of depression in systemic lupus erythematosus
Authors: Tayer Wendy G. , Nicassio Perry M. , Radojevic Vesna , Krall Teresa
Published: June 2011

Depression in systemic lupus erythematosus (SLE) is a common yet poorly understood phenomenon. This research adopted a biopsychosocial model in which pain and family support were hypothesized to predict depressive symptoms directly, and indirectly, through perceived helplessness. A total of 44 confirmed SLE patients recruited through the community completed a set of questionnaires in a cross‐sectional, correlation design. The results confirmed our model's applicability, demonstrating that high pain and high helplessness independently contributed to depression; however, the contribution of family support was not significant. While mixed support was found for a pain‐learned helplessness link, helplessness mediated the effects of patients' socio‐economic status on depression such that patients of lower socio‐economic status reported greater helplessness in the face of their illness. In summary, the data indicate that pain and helplessness are important concomitants of SLE‐related depression. Longitudinal research is recommended to clarify the relationships among these variables over time in clinical samples.
Dieting in adolescence: An application of the theory of planned behaviour
Authors: Conner Mark , Martin Eleanor , Silverdale Natalie , Grogan Sarah
Published: June 2011

This study examined self‐reported height and weight, self/body esteem, current‐ideal body figure discrepancy, dietary restraint, intentions to diet and underlying beliefs based upon the theory of planned behaviour in 128 11‐year‐olds (61 boys, 67 girls) and 103 13–14‐year‐olds (52 boys, 51 girls). Overall the sample showed low levels of restraint and intentions to diet, although there were a number of significant differences between the age‐sex groups. Restraint and intentions to diet were higher in the girls and restraint was more closely related to current‐ideal body figure discrepancy than actual degree of overweight. Intentions to diet, and restraint were significantly predicted by beliefs about the positive outcomes of dieting, conditions facilitating dieting, and pressure from the media to attain a slim body shape. These variables mediated the effects of actual weight, sex and age but not self/body esteem or current‐ideal body figure discrepancy on intentions and restraint.
Impaired cognitive processing in dieters: Failure of attention focus or resource capacity limitation?
Authors: Green Michael W. , Elliman Nicola A. , Rogers Peter J.
Published: June 2011

Objectives. The current study investigated the fundamental nature of the cognitive processing deficit associated with spontaneous dieting behaviour.

Design. In a between‐subjects design, dieters and non‐dieters performed a number of cognitive performance tasks designed to test the competing hypotheses that the deficit in performance previously observed in dieters is due either to resource capacity limitation or to a failure to maintain attentional focus.

Methods. Current dieters (N = 21), non‐dieting restrained eaters (N = 20) and non‐dieting low‐to‐medium restrained eaters (N = 28) completed measures of working memory span, attentional focus and motor speed. Participants also completed self‐report measures of dietary restraint, somatic sensation and affective state.

Results. Dieters displayed a significantly smaller working memory span than non‐dieting participants with a similar level of dietary restraint, which covaried with their self‐rated ‘Desite to eat’.

Conclusions. The cognitive impairments found to be associated with dieting behaviour result from a reduction in working memory processing capacity. It is suggested that this, in turn, results from task‐irrelevant cognitions concerning food preferentially consuming limited processing capacity.
A self‐determination theory approach to the study of intentions and the intention–behaviour relationship in children's physical activity
Authors: Chatzisarantis Nikos L. D. , Biddle Stuart J. H. , Meek Geoffrey A.
Published: June 2011

Objectives. Based on self‐determination theory, the present paper investigates relationships between behavioural regulations of physical activity in a school setting with intentions to exercise and actual exercising in leisure time. Moderating effects of personal experience of intentions (autonomous vs. controlled intentions) on the relationship between intentions to exercise and actual exercising in leisure time were also examined.

Design. A prospective study assessing psychological variables two weeks apart.

Method. Self‐report questionnaires distributed to children in two private and one state school. Assessments included five types of regulation of physical activities in school, intentions to exercise, subjective experience of intentions (‘integrated intentions’) and actual exercising during leisure time. Final N = 100.

Results. Consistency of intentions to exercise in leisure time and consistency between intentions to exercise and actual exercising in leisure time were a function of both controlling and autonomous forms of regulation of physical activity in schools. Intentions to exercise predicted actual exercising in leisure time when intentions were experienced as autonomous and not as controlled.

Conclusions. Adherence to the health behaviour of exercising can be promoted by supporting autonomy and avoiding control of the behaviour in children. The integration of self‐determination theory with social‐cognitive theories of social action can result in a more elaborated understanding of social and health behaviours.
Emotional distress and control cognitions as mediators of the impact of chronic pain on disability
Authors: Fisher Keren , Johnston Marie
Published: June 2011

Objectives. To explore the hypothesized mediating effects of cognitions and emotional distress on the pain‐disability relationship.

Design. Pain (McGill Pain Questionnaire), disability (Oswestry Low Back Pain Disability Questionnaire), emotional distress (General Health Questionnaire 28) and Locus of Control (Multidimensional Health Locus of Control) were examined by MANOVA for differences between admission to a pain rehabilitation programme and follow‐up and by correlation to examine inter‐relationships. Stepwise multiple regressions tested for the significant predictors of disability on admission and follow‐up and proportional change.

Methods. Seventy‐three patients met the criteria for inclusion (age between 16 and 65 years, low back pain for six months, English speaker). Fifty‐four patients were available for follow‐up. Patients attended a three‐week programme based on cognitive behavioural principles. Data were collected by self‐report on admission to the programme and at three‐month follow‐up.

Results. At follow‐up, disability, pain and emotional distress were all found to have improved. Admission, follow‐up and proportional change scores showed no correlation between pain and disability at any stage. However, distress and internal Locus of Control (IHLC) were related to disability and distress was also related to pain. Multiple regressions showed that IHLC and distress predicted disability on admission and follow‐up. Distress predicted the proportional change in disability.

Conclusions. No direct relationship was found between pain and disability. It appeared that IHLC modified, and emotional distress mediated, the pain‐disability relationship.
A METHOD FOR THE DETECTION OF MEANINGFUL AND REPRODUCIBLE GROUP SIGNATURES FROM GENE EXPRESSION PROFILES
Authors: LICAMELE LOUIS , GETOOR LISE
Published: June 2011

Gene expression microarrays are commonly used to detect the biological signature of a disease or to gain a better understanding of the underlying mechanism of how a group of drugs treat a specific disease. The outcome of such experiments, e.g. the signature, is a list of differentially expressed genes. Reproducibility across independent experiments remains a challenge. We are interested in creating a method that can detect the shared signature of a group of expression profiles, e.g. a group of samples from individuals with the same disease or a group of drugs that treat the same therapeutic indication. We have developed a novel Weighted Influence — Rank of Ranks (WIMRR) method, and we demonstrate its ability to produce both meaningful and reproducible group signatures.
Nanostructured Aerosol Particles: Fabrication, Pulmonary Drug Delivery, and Controlled Release
Authors: Jiang Xingmao , Cheng Yung-Sung , Smyth Hugh D. C.
Published: June 2011

Pulmonary drug delivery is the preferred route of administration in the treatment of respiratory diseases and some nonrespiratory diseases. Recent research has focused on developing structurally stable high-dosage drug delivery systems without premature release. To maximize the deposition in the desired lung regions, several factors must be considered in the formulation. The special issue includes seven papers deal with aerosol-assisted fabrication of nanostructured particles, aerosol deposition, nanoparticles pulmonary exposure, and controlled release.
Lability of IgE Levels Early in Life
Authors: N'guessan Koffi , Ternant David , Labarthe François , Watier Hervé
Published: June 2011

We report a case of a very fast and intriguing decrease in IgE concentrations after exclusion from the diet of any CM lysate in an unusual clinical presentation of cow's milk allergy in an infant. Analysis of IgE kinetics after allergen elimination suggests rapid cessation of IgE biosynthesis and a short IgE half-life.
Successful Treatment of Anterior Tracheal Necrosis after Total Thyroidectomy Using Vacuum-Assisted Closure Therapy
Authors: Philippe Grégory , Pichon Nicolas , Lerat Justine , Amiel Jean Bernard , Clavel Marc , Mathonnet Muriel
Published: June 2011

Total thyroidectomy involving the adjacent structures of the trachea can cause tracheal damage such as early tracheal necrosis. The authors describe the first case of anterior tracheal necrosis following total thyroidectomy treated using vacuum-assisted closure device. After two weeks of VAC  therapy, there was no evidence of ongoing infection and the trachea was partially closed around a tracheotomy cannula, removed after 3 months. The use of a VAC  therapy to reduce and close the tracheal rent and to create a rapid granulation tissue over tracheal structure appeared as a good opportunity after anterior tracheal necrosis.
The Role of Cilia in the Regulation of Bile Flow
Authors: LaRusso Nicholas F. , Masyuk Tetyana V.
Published: June 2011

Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, are ciliated cells. Each cholangiocyte has a primary cilium consisting of (i) a microtubule-based axoneme and (ii) the basal body, centriole-derived, microtubule-organizing center from which the axoneme emerges. Primary cilia in cholangiocytes were described decades ago, but their physiological and pathophysiological significance remained unclear until recently. We now recognize that cholangiocyte cilia extend from the apical plasma membrane into the bile duct lumen and, as such, are ideally positioned to detect changes in bile flow, bile composition and bile osmolality. These sensory organelles act as cellular antennae that can detect and transmit signals that influence cholangiocyte function. Indeed, recent data show that cholangiocyte primary cilia can activate intracellular signaling pathways when they sense modifications in the flow, molecular constituents and osmolarity of bile. Their ability to sense and transmit signals depends on the participation of a growing number of specific ciliary-associated proteins that act as receptors, channels and transporters. Cholangiocyte cilia, in addition to being important in normal biliary physiology, likely contribute to the cholangiopathies when their normal structure or function is disturbed. Indeed, the polycystic liver diseases that occur in combination with autosomal dominant and recessive polycystic kidney disease (i.e. ADPKD and ARPKD) are two important examples of such conditions. Recent insights into the role of cholangiocyte cilia in cystic liver disease using in vitro and animal models have already resulted in clinical trials that have influenced the management of cystic liver disease.
The Bile Acid Membrane Receptor TGR5: A Valuable Metabolic Target
Authors: Pols Thijs W.H. , Noriega Lilia G. , Nomura Mitsunori , Auwerx Johan , Schoonjans Kristina
Published: June 2011

Bile acids (BAs) are amphipathic molecules that facilitate the uptake of lipids, and their levels fluctuate in the intestines as well as in the circulation depending on food intake. Besides their role in dietary lipid absorption, BAs function as signaling molecules that activate specific BA receptors and trigger downstream signaling cascades. The BA receptors and the signaling pathways they control are not only important in the regulation of BA synthesis and their metabolism, but they also regulate glucose homeostasis, lipid metabolism and energy expenditure – processes relevant in the context of the metabolic syndrome. In addition to the function of the nuclear receptor FXRα in regulating local effects of BAs in the organs of the enterohepatic axis, increasing evidence points to a crucial role of the G-protein-coupled receptor TGR5 in mediating systemic actions of BAs. Here we review the current knowledge on BA receptors, with a strong focus on the cell membrane receptor TGR5, which has emerged as a promising target for intervention in metabolic diseases.
TGR5 in the Biliary Tree
Authors: Keitel Verena , Häussinger Dieter
Published: June 2011

Background/Aims: TGR5 is a plasma membrane-bound, G-protein-coupled receptor for bile acids. TGR5 mRNA has been detected in a variety of tissues, including liver. The aim of the present study was to determine the localization and function of the receptor in biliary epithelial cells. Methods: Liver and gallbladder tissue from humans and rodents were analyzed for TGR5 expression and localization by real-time PCR, Western blot and immunofluorescence microscopy. Cholangiocytes and gallbladder epithelial cells were isolated from wild-type and TGR5 knockout mice. Cyclic AMP (cAMP) was measured using a radioimmunoassay and chloride concentrations were analyzed using the chloride-sensitive dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE). Cell proliferation was determined by bromodeoxyuridine incorporation. Results: TGR5 is localized in the apical membrane and the primary cilium of cholangiocytes and gallbladder epithelial cells. Activation of the receptor by bile acids led to a rise in intracellular cAMP concentrations and a decrease in intracellular chloride concentrations as measured by MQAE fluorescence, indicating increased chloride secretion. This effect could be abolished in the presence of an inhibitor of the cAMP-dependent chloride channel cystic fibrosis transmembrane conductance regulator. Furthermore, activation of TGR5 by bile acids induced cholangiocyte proliferation, which was not observed in cells derived from TGR5 knockout mice. Conclusion: In biliary epithelial cells, TGR5 acts as a bile acid sensor coupling biliary bile acid concentrations to bile formation. Furthermore, the receptor may play a role in bile acid-dependent cholangiocyte proliferation and may protect biliary epithelial cells from bile acid-induced cell death.
Alterations of Hormonally Active Fibroblast Growth Factors after Roux-en-Y Gastric Bypass Surgery
Authors: Jansen Peter L.M. , van Werven Jochem , Aarts Edo , Berends Frits , Janssen Ignace , Stoker Jaap , Schaap Frank G.
Published: June 2011

Thirty-five morbidly obese patients underwent Roux-en-Y gastric bypass surgery (RYGB). In addition to weight loss, these patients showed significant improvement of insulin resistance and a reduction of hepatic fat content. Three months after surgery, the serum bile salts were slightly but significantly elevated, and the levels of the endocrine-acting fibroblast growth factor 19 (FGF19) and FGF21 were increased. FGF19 and FGF21 play a role as regulators of hepatic lipid and glucose metabolism. These results show that RYGB surgery improves metabolism and that this improvement is still apparent 3 months after surgery. Bile salts may play a key role in the improvement of metabolism after RYGB. Why serum bile salt concentrations are elevated after RYGB needs to be investigated.