bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes of parent-assisted social skills intervention for high-functioning children with autism spectrum disorders
Authors: Mandelberg Josh , Frankel Fred , Cunningham Tina , Gorospe Clarissa , Laugeson Elizabeth A
Published: August 2013

This study aims to evaluate the long-term outcome of Children’s Friendship Training, a parent-assisted social skills intervention for children. Prior research has shown Children’s Friendship Training to be superior to wait-list control with maintenance of gains at 3-month follow-up. Participants were families of children diagnosed with autism spectrum disorder who completed Children’s Friendship Training 1–5 years earlier. They were recruited through mail, phone, and email. Information collected included parent and child completed questionnaires and a phone interview. Data were collected on 24 of 52 potential participants (46%). With an average of 35-month follow-up, participants had a mean age of 12.6 years. Results indicated that participants at follow-up were invited on significantly more play dates, showed less play date conflict, improved significantly in parent-reported social skills and problem behaviors, and demonstrated marginally significant decreases in loneliness when compared to pre–Children’s Friendship Training.
Prevalence and correlates of postsecondary residential status among young adults with an autism spectrum disorder
Authors: Anderson Kristy A , Shattuck Paul T , Cooper Benjamin P , Roux Anne M , Wagner Mary
Published: August 2013

This study examined the prevalence and correlates of three living arrangements (with a parent or guardian, independently or with a roommate, or in a supervised setting) among a nationally representative sample of postsecondary young adults with an autism spectrum disorder. We assessed living arrangements since leaving high school. Compared with young adults with other disability types (learning disabilities, intellectual disabilities, or emotional disturbances), those with an autism spectrum disorder were more likely to have lived with a parent or guardian and least likely ever to have lived independently since leaving high school. Members of the autism spectrum disorder group were less likely to have ever lived elsewhere and more likely to live under supervision since leaving high school compared to persons with emotional disturbances and learning disabilities. Group differences persisted after controlling for functional ability and demographic characteristics. Correlates of residential independence included being White, having better conversation ability and functional skills, and having a higher household income. Further research is needed to investigate how these residential trends relate to the quality of life among families and young adults.
Treatment resistant depression in primary care: Co-constructing difficult encounters
Authors: McPherson Susan , Byng Richard , Oxley Donna
Published: August 2013

Many patients with depression do not recover despite medication or therapy. Individuals with treatment resistant depression often have co-morbid anxiety, personality difficulties and drug or alcohol misuse and have been characterised as difficult, heartsink or problem personalities by general practitioners. Yet critical studies of interaction in medical settings suggest that the context may have a role in constructing the patient. A total of 12 audio-recorded routine consultations were analysed following guidelines for qualitative analysis of medical discourse. The interpretation focused on ways in which the context and structure of primary care consultations in a UK setting construct difficult encounters, which may lead to patients with treatment resistant depression being seen as difficult to manage in various ways. Three overarching observations were that presentation of multiple problems in multiple domains clash with the consultation format; that patients’ atypically high level of activity in a time-limited setting prevents patient-centred work; that the question and answer format restricts multifaceted discussions of social and emotional problems, preventing shared understandings emerging. However, although interactions appear uneasy, they are repaired and may be moderately palliative. Suggestions are made for re-orienting general practitioner work with treatment resistant depression towards long-term goal setting outside of the traditional consultation structure in order to develop shared understandings.
Evaluation of ISO EN 13606 as a result of its implementation in XML
Authors: Austin Tony , Sun Shanghua , Hassan Taher , Kalra Dipak
Published: August 2013

The five parts of the ISO EN 13606 standard define a means by which health-care records can be exchanged between computer systems. Starting within the European standardisation process, it has now become internationally ratified in ISO. However, ISO standards do not require that a reference implementation be provided, and in order for ISO EN 13606 to deliver the expected benefits, it must be provided not as a document, but as an operational system that is not vendor specific. This article describes the evolution of an Extensible Markup Language (XML) Schema through three iterations, each of which emphasised one particular approach to delivering an executable equivalent to the printed standard. Developing these operational versions and incorporating feedback from users of these demonstrated where implementation compromises were needed and exposed defects in the standard. These are discussed herein. They may require a future technical revision to ISO EN 13606 to resolve the issues identified.
Increased electronic information sharing by sexual health services: Confidentiality and consent
Authors: Hunter Inga , Haining Ede Gael , Whiddett Richard
Published: August 2013

New Zealand is moving towards an integrated health-care model with information accessible electronically regardless of location, linking existing health provider systems, regional clinical results repositories and a shared care record. However, such information sharing has been a major concern for patients attending sexual health services. In this study, we investigated patient attitudes towards a change in practice to support an integrated care model. Outcomes showed that confidentiality remains a significant concern, and routine sharing of patient information may create barriers to attendance for some, leading to a potential increase in untreated infections. We conclude that sexual health services may be able to change their information management practices to an opt-out consent system and routinely share health information with other health providers, but further public discussion to ensure informed consent is needed before this can happen. Regardless of national policy, it is still necessary to keep clinic visit details confidential for some patients attending sexual health services.
The use of weblogs within palliative care: A systematic literature review
Authors: Ngwenya Nothando B , Mills Stella
Published: August 2013

The use of weblogs has had a huge impact within the healthcare sector, and palliative care users have found a way to express themselves using this technology. The objective of this article is to review current research on palliative care service users’ experience of using weblogs. A search was conducted in MEDLINE, PsycINFO and PubMed from 2002 to 2012 focusing on weblogs in palliative care. After extensive searches and assessment, six articles were included in the review. Results show that palliative care bloggers find blogging therapeutic and beneficial. Weblogs empowered individuals leading to health behaviour change while also giving them access to social support thus fostering well-being. However, there is lack of robust evidence showing the benefits of blogging using clinical measures or other scientific methods. Given the growth of these weblogs by palliative care patients, research is required to strengthen evidence for their benefit and to evaluate their effectiveness.
Effect of milling of C and Ti mixture as ceramic coating on the properties of 7Ch3 tool steel during plasma spray process
Authors: Razavi Mansour , Irankhah Reza , Rahimipour Mohammad Reza
Published: August 2013

In this study, the effect of milling time of processed powder coatings on the properties of 7Ch3 tool steel during plasma spray process was investigated. For this purpose, raw materials containing powders of titanium and carbon with stoichiometric ratio were milled and samples were taken in different time intervals. After phase investigations by X-ray diffraction, three milled samples as just mixed, activated and synthesized specimens were selected and coated on the substrate. The obtained results showed that titanium carbide can be successfully synthesized by mechanical alloying based on a gradual mechanism. Crystalline sizes of the synthesized carbide were found to be in nano-meter scale. Deposited coating leads to an increase in mechanical and wear properties of the substrate. The average sizes of coatings remained in nano-meter order too. Studies revealed that the sample which was coated by activated mixture had the best measured properties among the other specimens.
Paris offscreen: Chinese tourists in cinematic Paris
Authors: Dung Yun-An Olivia , Reijnders Stijn
Published: August 2013

This article examines from a European-Asian perspective the relationship between media representations and the tourist’s imagination. We use the case of Chinese tourists in Paris to investigate how these non-European tourists imagine Europe and how these imaginations are being realized, challenged and modified during concrete tourist experiences. Drawing on semi-structured interviews with tourists and field observations, this article shows how the Chinese tourist imagination of Europe is strongly influenced by popular representations from the media. More in particular, the Chinese tourist experience of Paris as it turns out is characterized by an ongoing negotiation between media-inspired fantasies and personal experiences of the ‘real’ Paris. As a result of this, the way the Chinese imagined Europe before their visit is reinforced, but also challenged. Chinese tourists tend to develop a hybrid perspective: they learn to re-appreciate Paris in its complexity while re-constituting their own cultural identity vis-a-vis the European Other.
‘Mine’s a Pint of Bitter’: Performativity, gender, class and representations of authenticity in real-ale tourism
Authors: Spracklen Karl , Laurencic Jon , Kenyon Alex
Published: August 2013

Leisure choices are expressive of individual agency around the maintenance of taste, boundaries, identity and community. This research article is part of a wider project designed to assess the social and cultural value of real-ale to tourism in the north of England. This article explores the performativity of real-ale tourism and debates about belonging in northern English real-ale communities. The research combines an ethnographic case study of a real-ale festival with semi-structured interviews with organisers and volunteers, northern English real-ale brewers and real-ale tourists visiting the festival. It is argued that real-ale tourism, despite its origins in the logic of capitalism, becomes a space where people can perform Habermasian, communicative leisure, and despite the contradictions of preferring some capitalist industries over others on the basis of their perceived smaller size and older age, real-ale fans demonstrate agency in their performativity.
On violence in Habermas’s philosophy of language
Authors: Ashenden Samantha
Published: August 2013

Habermas does not rule out the possibility of violence in language. In fact his account explicitly licenses a broad conception of violence as ‘systematically distorted communication’. Yet he does rule out the possibility that language simultaneously imposes as it discloses. That is, his argument precludes the possibility of recognizing that there is an antinomy at the heart of language and philosophical reason. This occlusion of the simultaneously world-disclosing and world-imposing character of language feeds and sustains Habermas’s legal and political arguments, where he states that in order to achieve consensus rational deliberation must eliminate force. In this paper, I claim that this argument operates through a manoeuvre that leaves Habermas’s position curiously blind to its own predicament. To explain why, I turn to Kant’s treatment of the problem of evil in Religion Within the Boundaries of Mere Reason. Here, as in the Western philosophical tradition more generally, evil has no separate existence: it is folded back into Kant’s philosophical scheme. Arendt notes that as soon as Kant identifies the problem of evil he rationalizes it into comprehensible motives. I will show how, through a move that is structurally similar to Kant’s rationalization of evil, Habermas rationalizes and attempts to eliminate violence from his consideration of law and language. In Habermas’s work, law and language appear as ciphers for reason. The case to be made here is that Habermas’s inability to recognize the paradoxical character of language and reason makes his work blind to the violence in which it is unavoidably implicated.
Do Colleges Get What They Pay For? Evidence on Football Coach Pay and Team Performance
Authors: Colbert Gary J. , Eckard E. Woodrow
Published: August 2013

We use a data set of Football Bowl Subdivision (Division-IA) universities to investigate the hypothesis that higher coach pay leads to improved team performance. Our analysis finds that pay and team performance are positively correlated and that, when schools change coaches, higher pay is associated with improved performance. The evidence suggests that additional rating points are increasingly valuable, perhaps over US$1 million for top teams. Our descriptive analysis reveals the median 2011 head coach pay of US$1.2 million, significant increases over our 2006-2011 study period, and large disparities among schools and conferences. We conclude that administrators perceive highly ranked football teams have significant value.
Relying on the Ground Game
Authors: Darr Joshua P. , Levendusky Matthew S.
Published: August 2013

Though elite-based campaign mobilization was thought to be dead just a few election cycles ago, it has come roaring back in recent years. The vast majority of this direct voter outreach is coordinated through campaign field offices. Despite the increasing importance of such activities, little is known about where campaigns choose to locate these field offices and what effect campaign offices have on election outcomes. We develop a theoretical argument about where candidates will locate these offices, and test our argument using data from recent elections. We also show that these field offices increase county-level vote share by approximately 1%, netting Obama approximately 275,000 additional votes in the 2008 election. We conclude by discussing the normative implications of increased campaign investment in field operations.
Stem cells of the lower limb: Their role and potential in management of critical limb ischemia
Authors: Hart Colin A , Tsui Janice , Khanna Achal , Abraham David J , Baker Daryll M
Published: August 2013

Peripheral arterial occlusive disease (PAOD) contributes to decreased exercise tolerance, poor balance, impaired proprioception, muscle atrophy and weakness, with advanced cases resulting in critical limb ischemia (CLI) where the viability of the limb is threatened. Patients with a diagnosis of CLI have a poor life expectancy due to concomitant cardio and cerebrovascular diseases. The current treatment options to avoid major amputation by re-establishing a blood supply to the limb generally have poor outcomes. Human skeletal muscle contains both multipotent stem cells and progenitor cells and thus has a capacity for regeneration. Phase I and II studies involving transplantation of bone marrow-derived progenitor cells into CLI limbs show positive effects on wound healing and angiogenesis; the increase in quiescent satellite cell numbers observed in CLI muscle may also provide a sufficient in vivo source of resident stem cells. These indigenous cells have been shown to be capable of forming multiple mesodermal cell lineages aiding the repair and regeneration of chronically ischemic muscle. They may also serve as a repository for autologous transplantation. The behavior and responses of the stem cell population in CLI is poorly understood and this review tries to elucidate the potential of these cells and their future role in the management of CLI.
Teaching human rights? ‘All hell will break loose!’
Authors: Cassidy Claire , Brunner Richard , Webster Elaine
Published: August 2013

Human rights education is a prominent concern of a number of international organisations and has been dominant on the United Nations’ agenda for the past 20 years. The UN Decade for Human Rights Education (1995–2004) has been followed by the World Programme for Human Rights Education (2005–ongoing) and the recently adopted UN Declaration on Human Rights Education and Training. This article shares findings from a project that aimed to gauge the knowledge of human rights education of students undertaking initial teacher education and childhood practice programmes at one university in Scotland. Students were invited to share their experiences of and attitudes towards human rights education. While some students were confident in their approach to human rights education, others identified barriers, including their own knowledge and the structures acting upon them as teachers. Initial conclusions suggest that education students feel ill-equipped to engage with human rights education and that this issue must be addressed in initial teacher education courses.
The Power of Meaningful Work
Authors: Raub Steffen , Blunschi Stephan
Published: August 2013

This paper develops and tests a model of the impact of employees’ awareness of corporate social responsibility (CSR) initiatives on perceived task significance and important attitudinal and behavioral work outcomes of service employees in the hospitality industry. Data from 211 employees of a United Kingdom–based hotel chain provide support for the concept that employees should be made aware of CSR actions. Results suggest that employees’ awareness of CSR activities is positively related to job satisfaction, engagement in helping and voice behavior, and personal initiative, and CSR awareness is negatively related to emotional exhaustion. These relationships are partly or fully mediated by perceived task significance. We discuss implications of this research for theory and practice, and provide several recommendations for how managers in the hospitality industry can increase employees’ awareness for corporate engagement in CSR initiatives.
The Efficacy of Sustainability Values in Predicting Travelers’ Choices for Sustainable Hospitality Businesses
Authors: Sirakaya-Turk Ercan , Baloglu Seyhmus , Mercado Haylee Uecker
Published: August 2013

Sustainability studies suggest that travelers’ decisions to support sustainable production and to consume sustainable hospitality and tourism services are functions of those travelers’ values. This study examined the efficacy of the sustainability value (SV) scale in predicting potential travelers’ choices for sustainable hospitality businesses using a partially mediated structural equation model. Data from a panel of 1,202 recent travelers in North America suggest that SVs predict an individual’s choice for sustainable hospitality businesses. The effect of those values, however, is partially mediated by the travelers’ environmental behaviors. Based on the respondents’ attitudes and behavior, they were grouped into an environment-supporting group called “strong-sustainers” and an environment-neutral group termed “centrists-sustainers.” Extending these findings to the market, hoteliers could offer targeted sustainability messages for the proposed “strong-sustainer” traveler, who would be more likely to purchase a “green” room, and likewise customize communications to the “centrist-sustainer” travelers, for whom an environmental message carries no weight.
Internal Rotation Behind-the-Back Angle
Authors: Sraj Shafic A.
Published: August 2013

Background:

The hand-behind-back method is the accepted technique to evaluate shoulder internal rotation, is highly popular, and is endorsed by the American Academy of Orthopaedic Surgeons. It remains, however, subject to intra- and interexaminer discrepancy and has been challenged by several recent publications.

Hypothesis:

Internal rotation behind the back can be evaluated with a measurable angle, which eliminates the need to estimate spinal level, decreases the effect of unrelated joints, and allows collection of numeric rather than categoric data.

Study Design:

Descriptive laboratory study.

Methods:

We defined the internal rotation behind-the-back (IRB) angle as that between the ulna and the line of gravity. A pendulum is attached to a standard goniometer. The patient is asked to reach the highest point along the midline of the back. The goniometer is centered over the pisiform, and the angle between the ulnar axis and the pendulum is measured. Two examiners assessed both shoulders of 60 volunteers with no shoulder pathology using this technique on 2 occasions. Both examiners were blinded to each other’s values. We applied the paired Student t test and calculated Pearson correlation coefficients and weighted Cohen kappa values.

Results:

The IRB angles ranged from 50° to 125°. The difference of the mean, as measured with the Student t test, was 0.6° (95% confidence interval: 0.1°, 1.3°) and 0.6° (95% confidence interval: −0.8°, 1.8°); the Pearson correlation coefficients were 0.98 and 0.92; and the weighted kappa values were 0.88 and 0.77 for interobserver and intraobserver analyses, respectively.

Conclusion:

The IRB angle is easy to measure, is reproducible, and does not rely on determination of spinal level. It provides numeric data and may eliminate some of the uncertainty associated with the estimation of spinal level.

Clinical Relevance:

The IRB angle may eliminate some of the uncertainty associated with the estimation of spinal level.
Muscle Changes in Aging
Authors: Siparsky Patrick N. , Kirkendall Donald T. , Garrett William E.
Published: August 2013

Muscle physiology in the aging athlete is complex. Sarcopenia, the age-related decrease in lean muscle mass, can alter activity level and affect quality of life. This review addresses the microscopic and macroscopic changes in muscle with age, recognizes contributing factors including nutrition and changes in hormone levels, and identifies potential pharmacologic agents in clinical trial that may aid in the battle of this complex, costly, and disabling problem.

Level of Evidence: Level 5.
Optimal treatment of laryngopharyngeal reflux disease
Authors: Martinucci Irene , de Bortoli Nicola , Savarino Edoardo , Nacci Andrea , Romeo Salvatore Osvaldo , Bellini Massimo , Savarino Vincenzo , Fattori Bruno , Marchi Santino
Published: August 2013

Laryngopharyngeal reflux is defined as the reflux of gastric content into larynx and pharynx. A large number of data suggest the growing prevalence of laryngopharyngeal symptoms in patients with gastroesophageal reflux disease. However, laryngopharyngeal reflux is a multifactorial syndrome and gastroesophageal reflux disease is not the only cause involved in its pathogenesis. Current critical issues in diagnosing laryngopharyngeal reflux are many nonspecific laryngeal symptoms and signs, and poor sensitivity and specificity of all currently available diagnostic tests. Although it is a pragmatic clinical strategy to start with empiric trials of proton pump inhibitors, many patients with suspected laryngopharyngeal reflux have persistent symptoms despite maximal acid suppression therapy. Overall, there are scant conflicting results to assess the effect of reflux treatments (including dietary and lifestyle modification, medical treatment, antireflux surgery) on laryngopharyngeal reflux. The present review is aimed at critically discussing the current treatment options in patients with laryngopharyngeal reflux, and provides a perspective on the development of new therapies.
High‐definition vs. standard‐definition endoscopy with indigo carmine for the in vivo diagnosis of colonic polyps
Authors: Longcroft‐Wheaton Gaius , Brown James , Cowlishaw David , Higgins Bernard , Bhandari Pradeep
Published: August 2013

Background

There is growing evidence that indigo carmine chromoendoscopy is effective for the in vivo diagnosis of colonic polyps. However, the impact of colonoscope resolution on diagnostic accuracy has not been investigated.

Objective

We aimed to compare the effectiveness of in vivo diagnosis of small colonic polyps using indigo carmine dye spray with standard‐definition and high‐definition colonoscopes.

Methods

Procedures were performed using Fujinon colonoscopes and EPX 4400 processor. Fujinon standard‐definition (SD) and high‐definition (HD) colonoscopes were used, with the endoscopist blinded to colonoscope definition. Polyps <10 mm were assessed using 0.2% indigo carmine dye spray, with the predicted diagnosis recorded. In each case the kind of colonoscope (SD or HD) was recorded. Polyps were removed and sent for histological analysis, with the pathologist blinded to the diagnosis made by the endoscopist. The predicted diagnosis was compared with the true histology to calculate the accuracy, sensitivity and specificity of in vivo assessment using either SD or HD scopes.

Results

In total 237 polyps <10 mm in size were examined. There was no statistically significant difference for any of the measured parameters between SD and HD assessments, with an accuracy, sensitivity and specificity of 89%, 91% and 87% with SD colonoscopes and 92%, 96% and 84% with HD colonoscopes.

Conclusions

The accuracy of in vivo assessment of small colonic polyps with indigo carmine dye spray is excellent with standard‐definition colonoscopes and is not improved with high‐definition colonoscopes.
Use of Self-Reported Adherence and Keeping Clinic Appointments as Predictors of Viremia in Routine HIV Care in the Gambia
Authors: Peterson Kevin , Menten Joris , Peterson Ingrid , Togun Toyin , Okomo Uduak , Oko Francis , Corrah Tumani , Jaye Assan , Colebunders Robert
Published: August 2013

We followed 205 HIV-infected adults on antiretroviral therapy for at least 12 weeks in a Gambian clinic, where routine viral load monitoring was performed. The 1- and 4-week self-reported adherence and timeliness in keeping to scheduled appointments were recorded at each visit. Seventy patients had measurable viremia between the 12th week and the 3rd year of therapy. Survival analysis of the first detectable viral load on therapy demonstrated an association with 4-week (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.5-4.3, P = .001) and 1-week (HR 1.9, 95% CI 1.1-3.3, P = .024) self-reported suboptimal adherence and with 1 to 15 days of late presentation for appointments (HR 1.6-1.8, P .027-.109). In a multiple regression model, only 4-week self-reported adherence remained as a significant predictor of viremia.
Safety and Acceptability of Couples HIV Testing and Counseling for US Men Who Have Sex with Men
Authors: Sullivan Patrick S. , White Darcy , Rosenberg Eli S. , Barnes Jasper , Jones Jeb , Dasgupta Sharoda , O’Hara Brandon , Scales Lamont , Salazar Laura F. , Wingood Gina , DiClemente Ralph , Wall Kristin M. , Hoff Colleen , Gratzer Beau , Allen Susan , Stephenson Rob
Published: August 2013

We tested a couples HIV testing and counseling (CHTC) intervention with male couples in Atlanta by randomizing eligible couples to receive either CHTC or separate individual voluntary HIV counseling and testing (iVCT). To evaluate the acceptability and safety of CHTC, main outcomes were satisfaction with the intervention and the proportions of couples reporting intimate partner violence (IPV) and relationship dissolution after the service. The results indicated that the service was very acceptable to men (median 7-item index of satisfaction was 34 for CHTC and 35 for iVCT, P = .4). There was no difference in either incident IPV (22% versus 17% for CHTC and iVCT, respectively, P = .6) or relationship dissolution (42% versus 51% for CHTC and iVCT, respectively, P = .5). Based on the preliminary data, CHTC is safe for male couples, and it is equally acceptable to iVCT for men who have main partners.
Parks as a Tool for HIV Management
Authors: Shacham Enbal , Hipp J. Aaron , Scheuermann Mary , Önen Nur , Overton E. Turner
Published: August 2013

Access to parks improves overall health outcomes in the general population. Given that HIV infection has become a chronic disease to manage, among populations engaged in medical care, parks may be promoted as physical activity opportunities in order to manage chronic comorbid conditions. We conducted a cross-sectional examination of the relationships between sociodemographic and biomedical characteristics to park proximity among 635 individuals receiving outpatient HIV care. The data collected included HIV-related biomarkers, depression, and diagnoses of other chronic diseases. The total acres of parks an individual is exposed within one-quarter mile from their home were assessed. The cohort included 635 individuals (67% men, 73% black, and 21% white, mean age 42 years). Unemployment was negatively associated with park availability. Park proximity was not associated with depression or HIV biomarkers. As yet, little effort has been committed to promoting park usage as a low-cost, sustainable method to addressing comorbidities among individuals with HIV.
Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
Authors: Migliorini Gabriele , Fiege Bettina , Hosking Fay J. , Ma Yussanne , Kumar Rajiv , Sherborne Amy L. , da Silva Filho Miguel Inacio , Vijayakrishnan Jayaram , Koehler Rolf , Thomsen Hauke , Irving Julie A. , Allan James M. , Lightfoot Tracy , Roman Eve , Kinsey Sally E. , Sheridan Eamonn , Thompson Pamela , Hoffmann Per , Nöthen Markus M. , Mühleisen Thomas W. , Eisele Lewin , Zimmermann Martin , Bartram Claus R. , Schrappe Martin , Greaves Mel , Stanulla Martin , Hemminki Kari , Houlston Richard S.
Published: August 2013

Key Points

Variation at 10p12.2 (PIP4K2A) and 10p14 (GATA3) influences ALL risk and tumor subtype. GATA3 genotype is a determinant of event-free survivorship.
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation
Authors: Cutler Corey , Multani Pratik , Robbins David , Kim Haesook T. , Le Thuy , Hoggatt Jonathan , Pelus Louis M. , Desponts Caroline , Chen Yi-Bin , Rezner Betsy , Armand Philippe , Koreth John , Glotzbecker Brett , Ho Vincent T. , Alyea Edwin , Isom Marlisa , Kao Grace , Armant Myriam , Silberstein Leslie , Hu Peirong , Soiffer Robert J. , Scadden David T. , Ritz Jerome , Goessling Wolfram , North Trista E. , Mendlein John , Ballen Karen , Zon Leonard I. , Antin Joseph H. , Shoemaker Daniel D.
Published: August 2013

Key Points

Molecular profiling was used to optimize an ex vivo modulation protocol with dmPGE2 for UCB transplantation. Pulse treatment of UCB with dmPGE2 is safe and may lead to accelerated UCB engraftment and preferential cord chimerism.
The role of infection in the pathogenesis of idiopathic pulmonary fibrosis
Authors: Molyneaux Philip L. , Maher Toby M.
Published: August 2013

Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact triggers, which initiate the fibrotic process, remain unknown. Infectious agents, including both viruses and bacteria, have the capacity to cause alveolar-epithelial cell injury and apoptosis. Relatively few studies have examined the role of infection in IPF. Those that have, point to viruses playing a key role as cofactors in the initiation and progression of IPF. There is also some evidence to suggest that viral infection may be responsible for a proportion of acute exacerbations of IPF. The role played by bacteria in the pathogenesis of IPF is less clear cut. Studies from other respiratory diseases suggest that alterations in the lung microbiome are associated with disease and that these changes influence disease behaviour. Emerging molecular microbiological techniques are making the study of microbial communities in the lung easier. It is hoped that by combining such techniques with the careful longitudinal phenotyping of patients with IPF, it will be possible to elucidate the role played by bacteria and viruses in the pathogenesis of the disease. If infection plays a causal role in IPF then it is possible that therapeutic strategies, utilising currently available antiviral or antibiotic drugs, may be effective in modifying the course of this devastating condition.
Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?
Authors: Seferian Andrei , Simonneau Gérald
Published: August 2013

Pulmonary arterial hypertension (PAH) is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the administration inconveniences, represent established therapies for severe cases of PAH. Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug. Sildenafil and tadalafil, two phosphodiesterase type-5 inhibitors, have shown improved exercise capacity by increasing the nitric oxide level. Riociguat, acting on the same nitric oxide pathway, as a guanylatecyclase activator, has shown promising results in clinical trials and will be available soon. Long-awaited results for tyrosin-kinase inhibitor, imatinib, as an antiproliferative therapy in PAH have been disappointing, due to severe adverse events. In conclusion, although it remains a disease with severe prognosis, the past 20 years have represented a huge progress in terms of treatments for PAH with interesting opportunities for the future.
Pulmonary hypertension in chronic interstitial lung diseases
Authors: Caminati Antonella , Cassandro Roberto , Harari Sergio
Published: August 2013

Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed “out-of-proportion” PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e.increased dyspnoea, low diffusion capacity) and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs.
Sex-specific lung diseases: effect of oestrogen on cultured cells and in animal models
Authors: Shim Bosung , Pacheco-Rodriguez Gustavo , Kato Jiro , Darling Thomas N. , Vaughan Martha , Moss Joel
Published: August 2013

Sex prevalence in lung disease suggests that sex-specific hormones may contribute to the pathogenesis and/or progression of at least some lung diseases, such as lung adenocarcinoma, lymphangioleiomyomatosis (LAM) and benign metastasising leiomyoma (BML). Oestrogen is an important hormone in normal lung development and in the pathogenesis of female predominant pulmonary diseases.In vivoandin vitrostudies have facilitated our understanding of disease pathogenesis and discovery of potential therapeutic targets. Oestrogen promoted disease progression in cell and animal models of lung adenocarcinoma, LAM and BML. Specifically, oestrogen enhanced tumour growth and metastasis in animal models of these diseases. Furthermore, 17β-estradiol (E2), the most abundant form of oestrogen in humans, increased the size and proliferation of cultured cells of lung adenocarcinoma and LAM. Coupled with the known mechanisms of oestrogen metabolism and signalling, these model systems may provide insights into the diverse effects of oestrogen and other hormones on lung diseases. Anti-oestrogen treatments that target key events of oestrogen synthesis or signalling, such as aromatase activity, oestrogen receptors and signalling pathways, may offer additional opportunities for clinical trials.
The importance of components of pulmonary rehabilitation, other than exercise training, in COPD
Authors: Hill Kylie , Vogiatzis Ioannis , Burtin Chris
Published: August 2013

Comprehensive pulmonary rehabilitation is an important component in the clinical management of people with chronic obstructive pulmonary disease (COPD). Although supervised exercise training is considered the cornerstone of effective pulmonary rehabilitation, there are many other components that should be considered to manage the impairments and symptom burden, as well as the psychosocial and lifestyle changes imposed by COPD. These include approaches designed to: 1) facilitate smoking cessation; 2) optimise pharmacotherapy; 3) assist with early identification and treatment of acute exacerbations; 4) manage acute dyspnoea; 5) increase physical activity; 6) improve body composition; 7) promote mental health; 8) facilitate advance care planning; and 9) establish social support networks. This article will describe these approaches, which may be incorporated within pulmonary rehabilitation, to optimise effective chronic disease self-management.
Chronic hypoventilation and its management
Authors: Simonds Anita K.
Published: August 2013

While obstructive sleep apnoea syndrome dominates discussion of the prevalence of sleep disordered breathing, nocturnal hypoventilation remains extremely prevalent in those with chronic ventilatory disorders and in the natural history of these conditions pre-dates the development of daytime ventilatory failure. In this review the clinical management of chronic hypoventilation in neuromuscular disease will be considered and then compared with that in obesity hypoventilation syndrome. In simple terms these conditions illustrate the polar opposite ends of the spectrum, as in neuromuscular disease the reduced capacity of the respiratory system is unable to withstand a normal respiratory load, and in obesity hypoventilation syndrome the normal capacity of the respiratory system is unable to tolerate a substantially increased ventilatory load.
Sleep disorders in COPD: the forgotten dimension
Authors: McNicholas Walter T. , Verbraecken Johan , Marin Jose M.
Published: August 2013

Sleep in chronic obstructive pulmonary disease (COPD) is commonly associated with oxygen desaturation, which may exceed the degree of desaturation during maximum exercise, both subjectively and objectively impairing sleep quality. The mechanisms of desaturation include hypoventilation and ventilation to perfusion mismatching. The consequences of this desaturation include cardiac arrhythmias, pulmonary hypertension and nocturnal death, especially during acute exacerbations. Coexistence of COPD and obstructive sleep apnoea (OSA), referred to as overlap syndrome, has been estimated to occur in 1% of the general adult population. Overlap patients have worse sleep-related hypoxaemia and hypercapnia than patients with COPD or OSA alone. OSA has a similar prevalence in COPD as in a general population of similar age, but oxygen desaturation during sleep is more pronounced when the two conditions coexist. Management of sleep-related problems in COPD should particularly focus on minimising sleep disturbanceviameasures to limit cough and dyspnoea; nocturnal oxygen therapy is not generally indicated for isolated nocturnal hypoxaemia. Treatment with continuous positive airway pressure alleviates hypoxaemia, reduces hospitalisation and pulmonary hypertension, and improves survival.
Drug-induced pulmonary arterial hypertension: a recent outbreak
Authors: Montani David , Seferian Andrei , Savale Laurent , Simonneau Gérald , Humbert Marc
Published: August 2013

Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH.
Sleep apnoea and metabolic dysfunction
Authors: Bonsignore Maria R. , Borel Anne-Laure , Machan Elizabeth , Grunstein Ron
Published: August 2013

Obstructive sleep apnoea (OSA) is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and non-alcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patients.
Chronic post-embolic pulmonary hypertension: a new target for medical therapies?
Authors: Delcroix Marion
Published: August 2013

The rationale for the use of pulmonary arterial hypertension-targeted drugs in chronic thromboembolic pulmonary hypertension is based on four bundles of evidence, as follows: 1) the pathobiology of the disease, with a distal component of pre-capillary arteriopathy that is very similar to pulmonary arterial hypertension; 2) the inoperability of some patients, and the persistence or recurrence of pulmonary hypertension after pulmonary endarterectomy in others; 3) the short-term efficacy and safety of pulmonary arterial hypertension-targeted drugs in these patients; and 4) their potential effect on survival. Chronic thromboembolic pulmonary hypertension is essentially a surgical disease, curable by pulmonary endarterectomy, with acceptable procedural mortality in experienced centres. Patient selection for surgery is extremely complex and results in 30–50% of patients considered inoperable. A large clinical experience has been built up with endothelin receptor antagonists and phosphodiesterase-5 inhibitors, while evidence from controlled trials is running far behind schedule. More recently, a randomised controlled trial with the guanylate cyclase stimulator, riociguat, achieved its target and showed haemodynamic, as well as functional, improvements within 4 months of therapy. The place of this therapy in the therapeutic arsenal needs to be further defined, but should be strictly limited to inoperable patients.
Common pathways in idiopathic pulmonary fibrosis and cancer
Authors: Vancheri Carlo
Published: August 2013

Idiopathic pulmonary fibrosis (IPF) is marked by a very disappointing survival rate and still represents a clinical dilemma. According to the current pathogenic hypothesis, chronic damage of the alveolar epithelium is followed by abnormal tissue repair and impairment of the alveolar structure. This process is driven by pathogenic events very similar to cancer, including epigenetic and genetic changes, altered response to regulatory signals, abnormal expression of microRNAs and activation of specific signalling pathways. IPF also resembles cancer with regard to its poor response to medical treatment and prognosis, which is very often worse than many cancers. We have hypothesised that IPF might be assimilated to a neoproliferative disorder of the lung. Viewing IPF as a cancer-like disease may satisfy the need for a better understanding of the pathogenesis of IPF by exploiting the large amount of knowledge that cancer biology evokes. The recognition of common pathogenic pathways between the two diseases may stimulate new clinical trials with cancer drugs, different drug combinations and different lines of drugs, as already experimented in oncology. Moreover, the concept of IPF as a cancer-like disorder may improve the attention given to this dreadful disease on a public, political and healthcare level.
Anti-interleukin-5 therapy in severe asthma
Authors: Garcia Gilles , Taillé Camille , Laveneziana Pierantonio , Bourdin Arnaud , Chanez Pascal , Humbert Marc
Published: August 2013

Asthma is a chronic inflammatory disorder of the airways that leads to acute symptoms, exacerbations and sometimes, for a small part of the asthmatic population, fatal or near-fatal exacerbations. This as yet significant minority of individuals present with severe asthma and have persisting daily symptoms, and exacerbations despite compliance with high doses of inhaled steroids and additional treatment. For more than a decade, the pharmacological management of patients with severe asthma has focused on evaluating specific cytokines. The rationale of this approach is based on the distinguished key role played by eosinophils in the asthma inflammatory processes. Eosinophils are recruited from the circulation to airways where they cause airway damageviadifferent mechanisms. Eosinophils are regulated in terms of their recruitment, activation, growth, differentiation and survival by interleukin (IL)-5. Abundant data fromin vitroexperiments, animal models and clinical trials has confirmed that IL-5 inhibition may be an effective approach for the treatment of asthma, especially severe asthma. Interfering with eosinophil function or reducing their numbers has been one of the most important goals of therapeutic monoclonal antibodies, which target cytokine receptor interactions in asthma, particularly IL-5. This review will consider new treatments options for severe asthma, particularly those targeting IL-5, that have already been evaluated in clinical trials in asthmatic patients.