bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the Seam Strength of Notched Webbings for Parachute Assemblies Using the Taguchi's Design of Experiment and Artificial Neural Networks
Authors: Onal Levent , Zeydan Mithat , Korkmaz Mahmut , Meeran Sheik
Published: February 2009

Webbings are used in parachute assemblies as reinforcing units for the strength they provide. The strength of these seams is an important characteristic which has a substantial influence on the mechanical property of the parachute assemblies. It is well established that factors such as fabric width, folding length of joint, seam design and seam type will all have an impact on seam strength. In this work, the effect of these factors on seam strength was studied using both Taguchi's design of experiment (TDOE) as well as an artificial neural network (ANN). In TDOE, two levels were chosen for the factors mentioned above. An L8 design was adopted and an orthogonal array was generated. The contribution of each factor to seam strength was analyzed using analysis of variance (ANOVA) and signal to noise ratio methods. From the analysis it was found that the fabric width, folding length of joint and interaction between the folding length of joint and the seam design affected seam strength significantly. Further, using TDOE, an optimal configuration of levels of factors was found. In order to contrast and compare the results from TDOE, an ANN was also used to predict seam strength using the above mentioned factors as inputs. The prediction from TDOE and ANN methodologies were compared with physical seam strength. It was established from these comparisons, in which the root mean square error was used as an accuracy measure, that the predictions by ANN were better in accuracy than those predicted by TDOE.
The Emerging Role of Antiarrhythmic Compounds With Atrial Selectivity in the Management of Atrial Fibrillation
Authors: McBride Brian F.
Published: February 2009

Atrial fibrillation represents a significant source of cardiovascular morbidity and mortality in the United States. Despite a relatively high clinical failure rate, pharmacologic conversion to and maintenance of normal sinus rhythm with antagonists of the HERG potassium channel responsible for carrying the delayed rectifier current IKr represent a mainstay of therapy. Suppression of IKr leads to restoration of normal sinus rhythm but is also associated with ventricular proarrhythmia. Given the unique electrophysiologic targets expressed in human atrium, compounds that exhibit selectivity for these targets have the potential to restore sinus rhythm with a reduced risk of ventricular proarrhythmia. Targets with expression limited to human cardiac atria and compounds that interact with these targets are reviewed.
Effects of Standard and Supratherapeutic Doses of Nelfinavir on Cardiac Repolarization: A Thorough QT Study
Authors: Damle Bharat , Fosser Cecilia , Ito Kaori , Tran Anh , Clax Pamela , Uderman Howard , Glue Paul
Published: February 2009

This was a randomized, 4‐way crossover, third‐party‐blinded study in 68 healthy subjects to assess the effect of nelfinavir on QTc interval. Treatments included (A) nelfinavir 1250 mg every 12 hours on days 1–4, (B) nelfinavir 1250 mg every 12 hours on days 1–3 plus 3125 mg on day 4, (C) placebo, and (D) moxifloxacin 400 mg every 24 hours on days 1–4. Pharmacokinetics and triplicate 12‐lead electrocardiograms were performed over 12 hours on days 1 and 4. Time‐matched, placebo‐subtracted, baseline‐adjusted changes in QT intervals with Fridericia's (QTcF) correction were determined following nelfinavir and moxifloxacin administration. Neither dose of nelfinavir had a clinically relevant effect on the QTcF interval on day 4 (primary endpoint) and day 1 because at every time point the upper 90% confidence limit was below 10 milliseconds and, furthermore, the mean difference was below 5 milliseconds. Additionally, there was no clinically relevant effect on QTcB (Bazett's correction), uncorrected QT, or the RR interval on days 1 or 4. Pharmacokinetics confirmed adequate systemic exposure to nelfinavir and moxifloxacin. While nelfinavir exposure was higher in poor compared with extensive metabolizers of CYP2C19 isozyme, there were no corresponding significant differences in QTcF change from placebo. At clinically relevant, doses nelfinavir is unlikely to cause QTc prolongation.
Pharmacokinetic and Pharmacodynamic Modeling of Pegylated Thrombopoietin Mimetic Peptide (PEG‐TPOm) After Single Intravenous Dose Administration in Healthy Subjects
Authors: Samtani Mahesh N. , Perez‐Ruixo Juan Jose , Brown Kathryn H. , Cerneus Dirk , Molloy Christopher J.
Published: February 2009

Pegylated thrombopoietin mimetic peptide (PEG‐TPOm) is a novel, potent thrombopoietin receptor agonist with low immunotoxicity potential that protects against chemotherapy‐induced thrombocytopenia in preclinical animal models. The aim of this study was to develop a population pharmacokinetic and pharmacodynamic model of PEG‐TPOm following single intravenous doses in healthy subjects. Data were obtained from a double‐blind, randomized, placebo‐controlled study. A model based on target‐mediated drug disposition and precursor pool life spans was applied. Model evaluation was performed through predictive checks and bootstrap analysis. The half‐life of PEG‐TPOm ranged between 18 and 36 hours, and the estimated distributional volume was 5 L. The increase in platelet counts was observed after a 4‐day delay, consistent with the megakaryocyte cell life span. The platelet life span was estimated to be 5 days. After maximum platelets counts were achieved on day 9, platelets returned back to baseline on day 29. Modelbased simulations were undertaken to explore pharmacodynamic effects after multiple dosing. Weekly dosing produced a sustained pharmacodynamic response, whereas an interdosing interval ≥2 weeks resulted in fluctuating pharmacodynamic profiles. Thus, the mechanistic pharmacokinetic/pharmacodynamic model was suitable for describing the complex PEG‐TPOm pharmacokinetics/pharmacodynamics, including target‐mediated disposition, dose‐dependent platelet stimulation, and mean life spans of thrombopoietic cell populations.
Similar Rivastigmine Pharmacokinetics and Pharmacodynamics in Japanese and White Healthy Participants Following the Application of Novel Rivastigmine Patch
Authors: Lefèvre Gilbert , Büche Monika , Sedek Greg , Maton Steve , Enz Albert , Lorch Ulrike , Sagan Cyriaque , Appel‐Dingemanse Silke
Published: February 2009

The pharmacokinetics and pharmacodynamics of rivastigmine were compared in Japanese and white healthy participants who were given ascending single doses of the novel rivastigmine transdermal patch. Rivastigmine patch strengths were 4.6 mg/24 h (5 cm2, 9 mg rivastigmine loaded dose), 9.5 mg/24 h (10 cm2, 18 mg), and 13.3 mg/24 h (15 cm2, 27 mg) (per label) or 7.0 mg/24 h (7.5 cm2, 13.5 mg) as a fall‐back dose. No relevant ethnic differences in the noncompartmental pharmacokinetics (parent and metabolite NAP226–90) and pharmacodynamics (plasma BuChE activity) of the rivastigmine patch were observed between Japanese and whites. However, drug exposure was slightly higher and inhibition of BuChE slightly more pronounced in Japanese participants than in whites, which was attributed to the lower body weight (ca. 11% less on average) of Japanese participants. Treatments were similarly well tolerated in both ethnic groups. In conclusion, no relevant ethnic differences in the intrinsic disposition or effects of rivastigmine delivered via transdermal route are expected between Japanese and white patients. The possible effect of body weight on drug exposure suggests that special attention should be paid to patients with very low body weight during up‐titration.
Quantitative Evaluation of Pharmacokinetic Inhibition of CYP3A Substrates by Ketoconazole: A Simulation Study
Authors: Zhao Ping , Ragueneau‐Majlessi Isabelle , Zhang Lei , Strong John M. , Reynolds Kellie S. , Levy Rene H. , Thummel Kenneth E. , Huang Shiew‐Mei
Published: February 2009

The US Food and Drug Administration draft drug interaction guidance recommends that 400 mg ketoconazole (KTZ) be administered once daily for several days (QD400) for maximal CYP3A inhibition. Some investigators suggest that a single dose of 400 mg (SD400) KTZ is sufficient given its short half‐life (t1/2∼ 3–5 hr). To determine the impact of KTZ regimens on CYP3A inhibition, we simulated AUC fold‐change (AUCR) in the presence of SD400, QD400, or 200 mg twice‐daily (BID200) KTZ for theoretical CYP3A substrates. Ratios of AUCR (AUCRQD400/AUCRSD400and AUCRBID200AUCRQD400) increase with increasing bioavailability and increasing substrate t1/2. The SD400 KTZ regimen may provide maximal inhibition only for a subset of substrates (ie, low bioavailability and short t1/2). For substrates with t1/2longer than that of KTZ, multiple KTZ dosing is critical and BID200 appears to provide greater inhibition than QD400. Also, timing of KTZ administration should be optimized to allow maximal presystemic enzyme inhibition prior to substrate administration.
Effects of Aspirin When Added to the Prostaglandin D2 Receptor Antagonist Laropiprant on Niacin‐Induced Flushing Symptoms
Authors: Dishy Victor , Liu Fang , Ebel David L. , Atiee George J. , Royalty Jane , Reilley Sandra , Paolini John F. , Wagner John A. , Lai Eseng
Published: February 2009

Niacin is an effective lipid‐modifying therapy whose use has been limited by suboptimal tolerability. The adverse effect of flushing is due to prostaglandin D2 (PGD2)–mediated cutaneous vasodilation. Adjunctive treatment with the PGD2 receptor antagonist laropiprant significantly reduces the incidence and severity of niacin‐induced flushing. The objective of this study was to assess the effect of aspirin pretreatment on flushing symptoms with extended‐release (ER) niacin/laropiprant in healthy volunteers. A randomized, double‐blind, placebo‐controlled crossover study compared patient‐rated flushing following pretreatment with aspirin 325 mg versus placebo administered 30 minutes before ER niacin 2 g/laropiprant 40 mg. Flushing responses were assessed using participant‐reported overall symptom severity score (OSSS), including individual characteristics of redness, warmth, tingling, or itching. The overall incidence and severity of flushing were comparable for participants receiving aspirin or placebo before ER niacin 2 g/laropiprant 40 mg. The difference in 3‐day average OSSS between treatments was 0.2 (P = .180). Profiles of flushing severity, frequency, and bothersomeness were comparable for the aspirin/ER niacin/laropiprant and ER niacin/laropiprant regimens. All treatments were safe and well tolerated. Coadministration of aspirin 325 mg daily with ER niacin 2 g/laropiprant 40 mg does not further reduce residual flushing symptoms associated with ER niacin 2 g/laropiprant 40 mg alone.
Assessment of the Effects of Renal Impairment on the Pharmacokinetic Profile of Fesoterodine
Authors: Malhotra Bimal , Gandelman Kuan , Sachse Richard , Wood Nolan
Published: February 2009

The effects of renal impairment on the pharmacokinetics of a single 4‐mg oral dose of fesoterodine are assessed in 8 healthy subjects and 8 subjects each with mild, moderate, or severe renal impairment. Compared with findings in healthy subjects, the maximum concentration in plasma of 5‐hydroxymethyl tolterodine (5‐HMT), the principal active moiety of fesoterodine, increases by 1.4‐, 1.5‐, and 2.0‐fold and area under the curve increases by 1.6‐, 1.8‐, and 2.3‐fold in subjects with mild, moderate, and severe renal impairment, respectively. There is a clear correlation between the renal clearance of 5‐HMT and creatinine clearance. The median time of observed maximum drug concentration (5–6 hours) and mean terminal half‐life (6–7 hours) of 5‐HMT are unaffected by renal impairment. The unbound fraction of 5‐HMT in plasma (0.43–0.54 ng/mL) is comparable across all groups. In conclusion, because of the involvement of both metabolic and renal elimination pathways, only modest increases in 5‐HMT exposures are observed in patients with renal impairment.
Comparison of Resting Energy Expenditure Prediction Methods With Measured Resting Energy Expenditure in Obese, Hospitalized Adults
Authors: Anderegg Brent A. , Worrall Cathy , Barbour English , Simpson Kit N. , DeLegge Mark
Published: February 2009

Background: Several methods are available to estimate caloric needs in hospitalized, obese patients who require specialized nutrition support; however, it is unclear which of these strategies most accurately approximates the caloric needs of this patient population. The purpose of this study was to determine which strategy most accurately predicts resting energy expenditure in this subset of patients. Methods: Patients assessed at high nutrition risk who required specialized nutrition support and met inclusion and exclusion criteria were enrolled in this observational study. Adult patients were included if they were admitted to a medical or surgical service with a body mass index ≥ 30 kg/m2. Criteria excluding patient enrollment were pregnancy and intolerance or contraindication to indirect calorimetry procedures. Investigators calculated estimations of resting energy expenditure for each patient using variations on the following equations: Harris‐Benedict, Mifflin–St. Jeor, Ireton‐Jones, 21 kcal/kg body weight, and 25 kcal/kg body weight. For nonventilated patients, the MedGem handheld indirect calorimeter was used. For ventilated patients, the metabolic cart was used. The primary endpoint was to identify which estimation strategy calculated energy expenditures to within 10% of measured energy expenditures. Results: The Harris‐Benedict equation, using adjusted body weight with a stress factor, most frequently estimated resting energy expenditure to within 10% measured resting energy expenditure at 50% of patients. Conclusion: Measured energy expenditure with indirect calorimetry should be employed when developing nutrition support regimens in obese, hospitalized patients, as estimation strategies are inconsistent and lead to inaccurate predictions of energy expenditure in this patient population.
Feasibility of Implementing a Reduced Fasting Protocol for Critically Ill Trauma Patients Undergoing Operative and Nonoperative Procedures
Authors: Pousman Robert M. , Pepper Colleen , Pandharipande Pratik , Ayers Gregory D. , Mills Beth , Diaz Jose , Collier Brian , Miller Rick , Jensen Gordon
Published: February 2009

Background: This prospective, observational cohort study was designed to determine the feasibility of implementing a reduced enteral fasting protocol in mechanically ventilated trauma patients undergoing selected operative and nonoperative procedures. Methods: Critically ill, mechanically ventilated trauma patients undergoing selected operative and nonoperative procedures received enteral nutrition up until the time of the procedure, if receiving small bowel feeds, or received enteral nutrition that was discontinued 45 minutes before the procedure, if receiving gastric feeds. Results: Measures of delivery of nutrition such as total enteral nutrition delivered and days required to reach nutrition goal were collected. Complications measured were death, incidence of ventilator‐associated pneumonia, urinary tract infection, catheter‐related bloodstream infection, wound infection, hypoglycemia, and emesis during procedures. No significant demographic differences were observed between the 2 groups. Patients in the intervention group showed trends toward greater total enteral nutrition delivered and faster attainment of target nutrition goals, although these measures were not statistically significant. Patients in the intervention group had rates of infective complications similar to those in the standard group. The median (interquartile range) for intensive care unit length of stay in the intervention group vs standard group was 7 (5, 15) vs 7 (5, 12) (P = 0.94), and the ventilator days were 8 (4.2, 14) vs 7 (3, 11) (P = 0.37). Conclusions: A reduced fasting protocol was feasible for selected operative procedures, with trends toward improving nutrition delivery and no increase in adverse outcomes. A larger randomized study of this approach is warranted before adoption of this practice can be advocated.
“Permission to Talk About It”
Authors: DePalma Renée , Atkinson Elizabeth
Published: February 2009

Based on practitioner interviews and action research, this article explores heteronormativity in U.K. primary schools, providing a performance venue where teachers' voices can be heard. Our particular focus on lesbian, gay, bisexual, and transgender (LGBT) equality in the primary school makes the voices of minority practitioners and equalities activists, generally expected to be silent in the school context, appear to sound particularly loud. Shifting the metaphor slightly from the oral to the visual realm, the unexpected visibility of those who were meant to remain invisible lends our participants what Patai calls surplus visibility; as the “Other,” they are forced to either disappear or appear larger than life, to keep silent, or scream. We have woven our participants' voices into an ethnographic narrative based on Patai's notion of surplus visibility, and the resulting play script is meant for public performance.
Would it Still be Possible to Identify Irradiated Lipid-containing Foods Towards the End of their Shelf-life?
Authors: Tewfik I. , Tewfik S.
Published: February 2009

The current British and European Standard (BS EN1785: 2003) for the identification of gamma irradiated foods is based on the isolation and detection of a group of lipid derived 2-alkylcyclobutanone compounds that are formed following irradiation. The 2-alkylcyclobutanones (2-dodecylcyclobutanone {DCB}, and 2-tetradecylcyclobutanone {TCB}) have been validated as radiolytic markers in the routine chemical identification of irradiated foods. This study was carried out with the view to answering a key question in relation to the fate of irradiated foods post irradiation and during storage; would it still be possible to correctly identify foods as having being irradiated towards the end of their shelf-life? Chemical detection method was employed to closely follow and plot the loss of each of these radiolytic markers throughout shelf-life. Significant levels of DCB and TCB were detected in all irradiated beef samples, which have been stored over 12-month period. Despite the considerable drop in the levels of both markers with time, it was still possible to detect both markers and therefore confirm that the stored samples had in fact been previously irradiated. These reported findings confer additional traceability choice to the global market of irradiated foods that may consequently, raise confidences among concerned parties.
Recovery of Bioactive Flavonols from Onion Solid Wastes Employing Water/Ethanol-Based Solvent Systems
Authors: Khiari Z. , Makris D.P. , Kefalas P.
Published: February 2009

Food processing by-products and wastes represent in many instances major polluting agents, since they bear a significant load of organic bio-molecules and particularly high chemical and biological oxygen demand (COD and BOD) levels. In this regard the development of processes that will aim at reducing the polluting load by removing added-value phytochemicals from agriculture-food wastes becomes imminent. In the present study, a first approach regarding the efficient recovery of bioactive flavonols from onion solid wastes has been attempted. Major flavonols were identified by liquid chromatography-mass spectrometry techniques and recovery was achieved by using environmentally friendly and food-compatible solvent systems, composed of water/ethanol, and acidified with either acetic or citric acid and HCl. Initial screening of various mixtures showed that significantly higher recoveries (P<0.001) can be attained by using 60% ethanol containing 0.1% HCl. The assessment of factors affecting yield, including extraction time and temperature, was accomplished using a series of extractions on the basis of a 3 × 3 factorial design model. The results obtained showed that maximization of yield is dependent upon increasing both extraction time and temperature.
Changes in Gene and Protein Expression during Tomato Ripening — Consequences for the Safety Assessment of New Crop Plant Varieties
Authors: Kok E.J. , Lehesranta S.J. , van Dijk J.P. , Helsdingen J.R. , Dijksma W.T.P. , Van Hoef A.M.A. , Koistinen K.M. , Karenlampi S.O. , Kuiper H.A. , Keijer J.
Published: February 2009

An important part of the comparative approach to assess the safety of new crop plant varieties is an extensive compositional analysis, including the measurement of all key nutrients and antinutrients in a specific crop. The study described here investigates the applicability of `omics' technologies, transcriptomics and proteomics, as additional tools in this comparative safety assessment. The aim of the work was to assess the extent of the natural variation in ripening tomato fruits as a model crop and to determine whether it is possible to develop simple `ripening stage' criteria for the sampling of fruits for `omics' analyses. It is shown that the set-up of an `omics' study is of crucial importance. Samples under scrutiny should be well-matched with relation to environmental conditions during growth and harvest, including the stage of ripening, as is stipulated in international guidance documents for the nutritional and toxicological assessment of genetically modified plants.
`Getting Out' in Ethnography
Authors: Iversen Roberta Rehner
Published: February 2009

In ethnography and related qualitative research that relies on naturalistic observation or fieldwork, `getting in', or accessing a research population or site, receives considerable attention, as do data collection and analysis and writing-up. Yet despite the recent increase in ethnographic publications and methodological sophistication across the globe, scant attention is paid to `getting out', or leaving the field. The exploration in this article stems from unexpected challenges to `getting out' that a team of nine researchers experienced during a five-year, five-city ethnographic research project in the USA. Given the growing emphasis on reflexivity in ethnography, the expanding mandates of institutional review boards, and the vigorous theoretical and methodological debates taking place in many countries, increased attention to `getting out', from multiple theoretical and epistemological perspectives and locations, could enrich the ethnographic research enterprise.
Using Context to Build Rigor
Authors: Armour Marilyn , Rivaux Stephanie L. , Bell Holly
Published: February 2009

There is no single guideline to assist researchers in creating high quality research within qualitative methods. This article proposes that rigor requires both a determination of actual or possible vulnerabilities and strategies that begin with an examination of the study itself rather than with a predetermined list of standardized practices. Two studies demonstrate how an inductive approach to rigor conducted within the framework of a particular qualitative approach, e.g. hermeneutic phenomenology, can produce greater thoroughness and understanding of a paradigm's epistemological assumptions. The studies include the lived experience of survivors of homicide victims, and women in substance abuse recovery.
`Infertile' Cameroonian Women
Authors: Weinger Susan
Published: February 2009

A small number of Cameroonian women spoke about the suffering they experience as `infertile' woman. Even though they raise children, they are still considered childless because of not producing biological offspring of their own. Assumed reasons for their `infertility' influence societal and self reactions. `Infertile' women are painfully aware of their need to be giving and acquiescent in order not to arouse the wrath of others. Still they receive derogatory comments and unfair societal demands, such as to work longer hours or share their money. These women explain the coping measures that they use in order to cope with this painful social marginalization.
Chiropractors and Vaccinations: Ethics is the Real Issue
Authors: Vernon Leonard F. , Kent Christopher
Published: February 2009

This article traces the historical and philosophical roots of the provaccination and anti-vaccination movements through to the present day, with a focus on the role of chiropractic within those movements. Political, legal, and scientific issues are considered. Attempts to portray the anti-vaccination chiropractors as unscientific extremists, by both orthodox medicine and from within the chiropractic community itself, clouds the informed consent and freedom of choice aspect relating to health care that they espouse, and scapegoats the so-called extremists rather than facing the ethical issues surrounding fully informed consent. The authors conclude that would-be medical ethicists promote their own political agendas that aid profit before safety and breed distrust within the community that is meant to be served in a balanced and ethical manner.
Review: Donepezil in Severe Alzheimer's Disease
Authors: Winblad Bengt
Published: February 2009

In the severe stages of Alzheimer's disease, functional autonomy is lost, psychiatric and behavioral symptoms become increasingly troublesome, and cognitive deficits increase until most patients require complete care, usually in specialized nursing homes. Consequently, some health care professionals question the benefits of pharmacologic intervention during these later stages. Since primary care physicians are often first to see these patients, they have key roles in recognizing the benefits of treatment and initiating appropriate management and referral. Three prospective randomized clinical trials of donepezil in severe Alzheimer's disease have been conducted; these show donepezil treatment is associated with functional and cognitive benefits, although behavioral benefits were not consistently observed. Donepezil was well tolerated; side effects were transient, mild to moderately severe, and cholinergic in nature. Donepezil has strong data throughout the Alzheimer's disease spectrum and, therefore, represents a first-line monotherapy that can provide benefits to patients in all stages of Alzheimer's disease.
Clinical academic research careers in nursing: towards global nursing
Authors: Kim Mi Ja
Published: February 2009

Abstract

Clinical academic research careers for nurses in the United Kingdom (UK) described in the Finch Report (2007) signals an important milestone in nursing research, education and practice. Unique aspects of this UK initiative is that it not only provides various awards for nurse research career pathways, but it also provides resources to establish infrastructure and positions for nurses to conduct research, teach, and practice in the clinical setting. Such an initiative merits serious consideration for its globalization.
Analysis of nursing research studies submitted to Spain’s health research fund and the resulting scientific output
Authors: Martín-Arribas María Concepción , González-Gil Teresa , Egea-Zerolo Blanca , García Raquel Hidalgo , Mallada Cristina Jones , Moreno-Casbas Teresa
Published: February 2009

Abstract

A descriptive observational study was conducted to ascertain and analyse the scientific status of nursing in Spain, based on nursing research studies submitted to the Health Research Fund ( Fondo de Investigación Sanitaria-FIS) for public funding and their ensuing scientific output. The study selection criteria required the following: the principal researcher to be a nurse; and the terms, ‘nursing’, ‘self-care’, ‘care’, ‘ulcer’ and/or ‘home care’ included in title or key words. For analysis of bibliographic output, a bibliographic search was made of national and international databases. During the study period (1996–2004), 673 nursing studies were submitted for public funding, with 28% being funded as a result. Of these, 37% addressed research topics focused on clinical practice. Most relied on quantitative methodology, with a descriptive design (48%). Of the studies funded from 1996 to 2002 (86), only 58% resulted in publications; of the total of 73 publications so yielded, only five were published in international journals. The main grounds for rejection of studies were also reviewed. Although nursing research is progressively increasing, it is essential to continue striving to enhance the quality and dissemination of such research.
The Constraints of Culture: Evidence from the Chicago Dyke March
Authors: Brown-Saracino Japonica , Ghaziani Amin
Published: February 2009

Drawing on an ethnographic study of the Chicago Dyke March, this article focuses on an instance in which a movement's ideology and identity contradict in order to advance, the theoretical question of how culture `works'. In forming as a reaction to perceived exclusions by the national and annual Gay Pride parades, Dyke March organizers developed an ideological commitment to inclusion.This ideology affected the March in three key areas: constructing an organizing structure, establishing recruitment and outreach procedures, and engaging in framing processes. However, the Dyke March's broad ideological commitment to inclusion conflicted with organizers' narrower collective identity, which formed around and celebrated a specific type of movement participant, and thus undermined their mobilization efforts. This study suggests that organizational dilemmas can arise for movements when their culture has internally contradictory elements. It introduces new theoretical perspectives about the conditions under which cultural elements work more or less effectively.
Argument Forms, Frames, and Value Conflict: Persuasion in the Case of Same-Sex Marriage
Authors: Ghoshal Raj
Published: February 2009

Is telling stories politically effective? Recent debates around the efficacy of storytelling have challenged the view that narratives are an effective means of political persuasion. This article empirically examines the persuasiveness of narratives through the lens of recent controversies over same-sex marriage. Through a survey-experiment, I test the effects of different kinds of arguments on heterosexuals' views on same-sex marriage. I find some support for long-standing claims of the efficacy of stories; however, stories are not always effective, and their perceived efficacy outstrips their actual efficacy.The findings suggest that narrative appeals along with non-narrative appeals that directly challenge ideas of same-sex marriage as inherently a religious issue are most likely to induce greater favourability toward same-sex marriage.The results help specify the types of issues for which narrative appeals might be expected to be effective, ineffective, or counterproductive, and further illuminate cultural dimensions of debates over same-sex marriage.
Beyond `La Dolce Vita': Bourdieu, Market Heteronomy and Cultural Homogeneity
Authors: Thorpe Christopher
Published: February 2009

This article takes the main arguments made by Bourdieu in his late work On Television and Journalism and applies them to the empirical case of the production of discursive visions of Italy and the Italians in Britain from approximately 1840 to the present day. In doing so, Bourdieu's field theory is applied in order to examine and compare the range and diversity of the Italian visions produced at around the mid-point of the 19th century — a period of high cultural autonomy in England — with those produced in the present day. In the account of the present day, the dominant assemblage of discursive practices and the fields from which they derive is explicated and the extent to which these visions are shaped by the `audience ratings' mindset is scrutinized.The article concludes by reflecting on the analytical utility of Bourdieu's field theory for understanding inter-cultural representation.
Targeting the Notch1 and mTOR pathways in a mouse T-ALL model
Authors: Cullion Kathleen , Draheim Kyle M. , Hermance Nicole , Tammam Jennifer , Sharma Vishva M. , Ware Christopher , Nikov George , Krishnamoorthy Veena , Majumder Pradip K. , Kelliher Michelle A.
Published: February 2009

Mutations in NOTCH1 are frequently detected in patients with T-cell acute lymphoblastic leukemia (T-ALL) and in mouse T-ALL models. Treatment of mouse or human T-ALL cell lines in vitro with γ-secretase inhibitors (GSIs) results in growth arrest and/or apoptosis. These studies suggest GSIs as potential therapeutic agents in the treatment of T-ALL. To determine whether GSIs have antileukemic activity in vivo, we treated near-end-stage Tal1/Ink4a/Arf+/− leukemic mice with vehicle or with a GSI developed by Merck (MRK-003). We found that GSI treatment significantly extended the survival of leukemic mice compared with vehicle-treated mice. Notch1 target gene expression was repressed and increased numbers of apoptotic cells were observed in the GSI-treated mice, demonstrating that Notch1 inhibition in vivo induces apoptosis. T-ALL cell lines also exhibit PI3K/mTOR pathway activation, indicating that rapamycin may also have therapeutic benefit. When GSIs are administered in combination with rapamycin, mTOR kinase activity is ablated and apoptosis induced. Moreover, GSI and rapamycin treatment inhibits human T-ALL growth and extends survival in a mouse xenograft model. This work supports the idea of targeting NOTCH1 in T-ALL and suggests that inhibition of the mTOR and NOTCH1 pathways may have added efficacy.
Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia
Authors: Bellon Marcia , Lepelletier Yves , Hermine Olivier , Nicot Christophe
Published: February 2009

Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive lymphoproliferative disease. MicroRNAs (miRNAs) are differentially expressed during hematopoiesis and lineage commitment of hematopoietic stem cell progenitors (HSCPs). Here, we report aberrant expression of hematopoietic-specific miR-223, miR-181a, miR-150, miR-142.3p, and miR-155 in HTLV-I–infected cells in vitro and uncultured ex vivo ATL cells. Our results suggest that HTLV-I–infected cells have an unbalanced expression of miRNA that favors T-cell differentiation. We also found altered expression of miRNA previously recognized as innate immunity regulators: miR-155, miR-125a, miR-132, and miR-146. Strikingly, our data also revealed significant differences between ex vivo ATL tumor cells and in vitro HTLV-I cell lines. Specifically, miR-150 and miR-223 were up-regulated in ATL patients but consistently down-regulated in HTLV-I cell lines, suggesting that ATL cells and in vitro–established cells are derived from distinct cellular populations.
Granulomatous angiitis leading to a pulmonary veno-occlusive disease-like picture
Authors: Dwyer N. , Smith R. , Challis D. , Reid D. , Kilpatrick D.
Published: February 2009

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension characterised by extensive fibrotic occlusion of pulmonary veins. PVOD has a similar insidious presentation to idiopathic pulmonary arterial hypertension but responds poorly to conventional therapies and has a worse prognosis.

The current study reports the case of a Caucasian female with a long history of progressive dyspnoea ultimately diagnosed as focal granulomatous venulitis leading to a pulmonary veno-occlusive disease-like pathology. The present study highlights the challenges in diagnosing and treating this condition.
Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia
Authors: Daniels J. M. A. , Vonk-Noordegraaf A. , Janssen J. J. W. M. , Postmus P. E. , van Altena R.
Published: February 2009

Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB.

There are several reports suggesting that imatinib might impair the immune system, leading to a variety of infections, including varicella zoster and hepatitis B. Control of TB in healthy individuals is achieved through acquired immunity, in which antigen-specific T-cells and macrophages arrest growth ofMycobacterium tuberculosisbacilli and maintain control over persistent bacilli. In the chronic stage of the infection, CD8+ T-cells assist macrophages in controlling intracellular mycobacteria. The T-cell receptor orchestrates this process.

The fact that tyrosine kinases play an important role in T-cell receptor signal transduction and that imatinib has been shown to affect T-cell receptor signal transduction, presents a mechanism by which imatinib might impair control ofMycobacterium tuberculosis; thereby leaving the host susceptible to reactivation of tuberculosis.
COPD in Chinese nonsmokers
Authors: Zhou Y. , Wang C. , Yao W. , Chen P. , Kang J. , Huang S. , Chen B. , Wang C. , Ni D. , Wang X. , Wang D. , Liu S. , Lu J. , Zheng J. , Zhong N. , Ran P.
Published: February 2009

Little is known about chronic obstructive pulmonary disease (COPD) in Chinese nonsmokers. The present study aimed to investigate the profiles of COPD among nonsmokers based on the Chinese Epidemiological Survey of COPD (CESCOPD).

In the CESCOPD, 20,245 subjects aged 40 yrs or older were interviewed with questionnaires and spirometry tests. Subjects with a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio of <0.70 were identified as having COPD. Data of 12,471 nonsmokers and 1,024 smoking COPD patients were analysed in the current study.

The overall prevalence of COPD among nonsmokers was 5.2% (95% confidence interval 4.8–5.6). Being male, of advanced age, lower body mass index (BMI) and lower educational level, having exposure to environmental tobacco smoke, coal and/or biomass smoke, poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough were all independently associated with a higher risk of having COPD among nonsmokers. Nonsmokers with respiratory symptoms without airflow limitation showed a somewhat different pattern of risk factors. Nonsmokers with COPD were less likely to present with chronic productive coughs and lower BMI, while more likely to have received a physician diagnosis of asthma and respiratory diseases in childhood, than smokers with COPD.

Chronic obstructive pulmonary disease is prevalent among Chinese nonsmokers, and nonsmoking chronic obstructive pulmonary disease may have different profiles from smoking chronic obstructive pulmonary disease.
Fenfluramine-like cardiovascular side-effects of benfluorex
Authors: Boutet K. , Frachon I. , Jobic Y. , Gut-Gobert C. , Leroyer C. , Carlhant-Kowalski D. , Sitbon O. , Simonneau G. , Humbert M.
Published: February 2009

Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects.

The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2–49 kg·m−2.

No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.
Impact of resistance to first-line and injectable drugs on treatment outcomes in MDR-TB
Authors: Hwang S. S. , Kim H-R. , Kim H. J. , Kim M. J. , Lee S. M. , Yoo C-G. , Kim Y. W. , Han S. K. , Shim Y-S. , Yim J-J.
Published: February 2009

Recently, resistance to additional first-line and injectable drugs was reported to be an independent risk factor for adverse outcomes in multidrug-resistant (MDR) tuberculosis (TB) patients. The aim of the present study was to confirm these observations in MDR-TB patients without HIV infection.

MDR-TB patients treated at a tertiary referral hospital in South Korea between January 1996 and December 2005 were included. The unadjusted and adjusted odds ratios of adverse treatment outcome were calculated for resistance to each drug and combination of drugs using simple or multiple logistic regressions.

None of the resistance to additional first-line or injectable drugs was associated with higher odds for adverse treatment outcome in 155 MDR but nonextensively drug-resistant (non-XDR) TB patients. However, streptomycin resistance was associated with 12 times the odds for adverse treatment outcome in 42 extensively drug-resistant (XDR) TB patients. Neither combinations of first-line drugs nor those of injectable drugs were associated with increased odds for adverse treatment outcomes in non-XDR MDR-TB patients or XDR-TB patients.

Only streptomycin resistance among the first-line or injectable drugs was associated with adverse treatment outcomes in extensively drug-resistant tuberculosis patients without HIV infection.
Early proximal lung cancer diagnosis and treatment
Authors: McWilliams A. , Lam B. , Sutedja T.
Published: February 2009

Lung cancer remains the largest cause of cancer deaths worldwide and the overall 5-yr survival rate is only 15%. This is because the majority of the lung cancers are diagnosed at late stages and the treatment outcome is suboptimal. However, the survival of patients with early stage proximal lung cancer is excellent and with advancements in technology we are currently well equipped to diagnose and stage these lung cancers. Together with the application of local bronchoscopic therapeutic modalities that may potentially cure early stage intraluminal lesions, there is expanding interest in the further exploration of new avenues for early detection, localisation, staging, treatment and close surveillance of these high-risk patients who are suffering from chronic field carcinogenesis. The present article will deal with various issues regarding early detection, staging and treatment of centrally located early stage, mostly squamous type, lung cancer.
The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome
Authors: Riha R. L. , Gislasson T. , Diefenbach K.
Published: February 2009

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common condition affecting ∼2–4% of the middle-aged population. A hereditary component to the condition has long been recognised but its genetic basis has been difficult to elucidate. Progress in determining the genotype of OSAHS is hampered by the lack of a consistent definition of phenotype and the large environmental influences on its expression. “Intermediate phenotypes”, such as craniofacial structure, obesity and upper airway control, have been utilised. Multiple gene polymorphisms have been explored in association with the latter, as well as with the sequelae of OSAHS, such as hypertension and increased insulin resistance. To date, two genome-wide scans have identified potential regions that may be of interest in further defining the intermediate phenotypes. The present paper focuses on human studies with an update of the most recent work in the area, including a short discussion on methods of genetic studies.
High-altitude pulmonary hypertension: Table. 1—
Authors: Xu X-Q , Jing Z-C.
Published: February 2009

High-altitude pulmonary hypertension (HAPH) is a specific disease affecting populations that live at high elevations. The prevalence of HAPH among those residing at high altitudes needs to be further defined. Whereas reduction in nitric oxide production may be one mechanism for the development of HAPH, the roles of endothelin-1 and prostaglandin I2pathways in the pathogenesis of HAPH deserve further study.

Although some studies have suggested that genetic factors contribute to the pathogenesis of HAPH, data published to date are insufficient for the identification of a significant number of gene polymorphims in HAPH.

The clinical presentation of HAPH is nonspecific. Exertional dyspnoea is the most common symptom and signs related to right heart failure are common in late stages of HAPH. Echocardiography is the most useful screening tool and right heart catheterisation is the gold standard for the diagnosis of HAPH. The ideal management for HAPH is migration to lower altitudes. Phosphodiesterase 5 is an attractive drug target for the treatment of HAPH.

In addition, acetazolamide is a promising therapeutic agent for high-altitude pulmonary hypertension. To date, no evidence has confirmed whether endothelin-receptor antagonists have efficacy in the treatment of high-altitude pulmonary hypertension.
Paediatric pulmonary hypertension: monitoring progress and identifying unmet needs
Authors: Beghetti M.
Published: February 2009

Recent advances in the field of pulmonary hypertension (PH) have provided clinicians with a range of treatment options, but effective disease management in children presents a unique challenge. The present article will discuss the steps being taken to address unmet needs in paediatric PH.

Understanding the epidemiology of paediatric PH is essential to guide management decisions, but such epidemiological data are scarce. The first international paediatric PH registry, Tracking Outcomes in Paediatric Pulmonary Hypertension (TOPP), promises to become a vital resource.

Studies of PH therapies are rare in children, and treatment of paediatric PH is generally guided by the adult treatment algorithm, with some adaptations. However, invasive management options, such as continuous prostacyclin infusion, even if effective, are challenging in children, and further research is required to develop appropriate treatment strategies, formulations and doses for paediatric PH. Measures of treatment success must also be defined, and the applicability of end-points from adult clinical studies remains an open question.

In summary, further epidemiological and treatment data are needed for paediatric pulmonary hypertension. The international TOPP registry will provide a valuable insight, but this must be complemented by research and development of adapted paediatric therapies. Dedicated childhood pulmonary hypertension services would optimise the diagnosis and management of this life-threatening disease.
Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options
Authors: Lang I. M.
Published: February 2009

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk.

Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a “dual” pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension.

Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met.

More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.