bluuebunny/crossref_metadata_2025 huggingface dataset:
The Meaning of AIDS-Related Deaths in an Urban Town in Ghana
Authors: Ohemeng Fidelia N. A.
Published: July 2015

HIV/AIDS has claimed the lives of many people, the majority of whom are young. In Ghana, about 200,000 people have lost their lives to the disease. While HIV/AIDS as a disease has enjoyed considerable academic scholarship, understanding how people make sense of death has not received adequate academic attention. This article explores the meaning of death resulting from AIDS in an urban town in Ghana. The views of 25 persons living with HIV/AIDS were solicited through in-depth interviews. Additional data were obtained from focus group discussions with members of the community in which the 25 persons were interviewed. The findings indicate that death from AIDS is seen as disgraceful and shameful. The meaning of AIDS deaths was based on the fact that HIV/AIDS is a metaphor for moral decadence. This image is subsequently projected onto its death. The classification of AIDS death as disgraceful and shameful may have implications for the funeral rites of AIDS patients, while at the same time affecting prevention and treatment.
Development and Validation of MMPI-2-RF Scales for Indexing Triarchic Psychopathy Constructs
Authors: Sellbom Martin , Drislane Laura E. , Johnson Alexandria K. , Goodwin Brandee E. , Phillips Tasha R. , Patrick Christopher J.
Published: July 2015

The triarchic model characterizes psychopathy in terms of three distinct dispositional constructs of boldness, meanness, and disinhibition. The model can be operationalized through scales designed specifically to index these domains or by using items from other inventories that provide coverage of related constructs. The present study sought to develop and validate scales for assessing the triarchic model domains using items from the Minnesota Multiphasic Personality Inventory–2–Restructured Form (MMPI-2-RF). A consensus rating approach was used to identify items relevant to each triarchic domain, and following psychometric refinement, the resulting MMPI-2-RF-based triarchic scales were evaluated for convergent and discriminant validity in relation to multiple psychopathy-relevant criterion variables in offender and nonoffender samples. Expected convergent and discriminant associations were evident very clearly for the Boldness and Disinhibition scales and somewhat less clearly for the Meanness scale. Moreover, hierarchical regression analyses indicated that all MMPI-2-RF triarchic scales incremented standard MMPI-2-RF scale scores in predicting extant triarchic model scale scores. The widespread use of MMPI-2-RF in clinical and forensic settings provides avenues for both clinical and research applications in contexts where traditional psychopathy measures are less likely to be administered.
Measurement Invariance and the Five-Factor Model of Personality
Authors: Rollock David , Lui P. Priscilla
Published: July 2015

This study examined measurement invariance of the NEO Five-Factor Inventory (NEO-FFI), assessing the five-factor model (FFM) of personality among Euro American ( N = 290) and Asian international ( N = 301) students (47.8% women, Mage = 19.69 years). The full 60-item NEO-FFI data fit the expected five-factor structure for both groups using exploratory structural equation modeling, and achieved configural invariance. Only 37 items significantly loaded onto the FFM-theorized factors for both groups and demonstrated metric invariance. Threshold invariance was not supported with this reduced item set. Groups differed the most in the item–factor relationships for Extraversion and Agreeableness, as well as in response styles. Asian internationals were more likely to use midpoint responses than Euro Americans. While the FFM can characterize broad nomothetic patterns of personality traits, metric invariance with only the subset of NEO-FFI items identified limits direct group comparisons of correlation coefficients among personality domains and with other constructs, and of mean differences on personality domains.
Item Response Theory Analysis of ADHD Symptoms in Children With and Without ADHD
Authors: Li James J. , Reise Steven P. , Chronis-Tuscano Andrea , Mikami Amori Yee , Lee Steve S.
Published: July 2015

Item response theory (IRT) was separately applied to parent- and teacher-rated symptoms of attention-deficit/hyperactivity disorder (ADHD) from a pooled sample of 526 six- to twelve-year-old children with and without ADHD. The dimensional structure ADHD was first examined using confirmatory factor analyses, including the bifactor model. A general ADHD factor and two group factors, representing inattentive and hyperactive/impulsive dimensions, optimally fit the data. Using the graded response model, we estimated discrimination and location parameters and information functions for all 18 symptoms of ADHD. Parent- and teacher-rated symptoms demonstrated adequate discrimination and location values, although these estimates varied substantially. For parent ratings, the test information curve peaked between −2 and +2 SD, suggesting that ADHD symptoms exhibited excellent overall reliability at measuring children in the low to moderate range of the general ADHD factor, but not in the extreme ranges. Similar results emerged for teacher ratings, in which the peak range of measurement precision was from −1.40 to 1.90 SD. Several symptoms were comparatively more informative than others; for example, is often easily distracted (“Distracted”) was the most informative parent- and teacher-rated symptom across the latent trait continuum. Clinical implications for the assessment of ADHD as well as relevant considerations for future revisions to diagnostic criteria are discussed.
A Moral Panic? The Problematization of Forced Marriage in British Newspapers
Authors: Anitha Sundari , Gill Aisha K.
Published: July 2015

This article examines the British media’s construction of forced marriage (FM) as an urgent social problem in a context where other forms of violence against women are not similarly problematized. A detailed analysis of four British newspapers over a 10-year period demonstrates that media reporting of FM constitutes a moral panic in that it is constructed as a cultural problem that threatens Britain’s social order rather than as a specific form of violence against women. Thus, the current problematization of FM restricts discursive spaces for policy debates and hinders attempts to respond to this problem as part of broader efforts to tackle violence against women.
Business Models for Sustainability From a System Dynamics Perspective
Authors: Abdelkafi Nizar , Täuscher Karl
Published: July 2015

To achieve sustainability, a firm has to transform its entire business logic. A business model for sustainability (BMfS) aims at creating value for various stakeholders and the natural environment. This article advances the current understanding of the basic functioning of BMfS by applying a systems perspective. Our BMfS understanding incorporates the natural environment as an essential element, but does not deal with sustainability from a broad perspective. The core logic of a BMfS is built upon the creation of a reinforcing feedback loop between the created value to the customers, the value captured by the firm, and the value to the natural environment. Consequently, we develop a graphical model based on system dynamics notation. First, we conceptualize the basic feedback loops. Then, we propose partial models for the firm, natural environment, entrepreneur/manager, and customer, and then integrate these partial models within a systemic, multilevel model. Finally, we generate propositions that combine insights from the model and extant literature.
Assessment of a quantitative 5' nuclease real-time polymerase chain reaction using the nicotinamide adenine dinucleotide dehydrogenase gamma subunit (nuoG) for Bartonella species in domiciled and stray cats in Brazil
Authors: André Marcos Rogério , Dumler John Stephen , Herrera Heitor M , Gonçalves Luiz R , de Sousa Keyla CM , Scorpio Diana Gerardi , de Santis Ana Cláudia Gabriela Alexandre , Domingos Iara Helena , de Macedo Gabriel Carvalho , Machado Rosangela Zacarias
Published: July 2015

Objectives

The objective of this study was to develop a quantitative 5' nuclease real-time polymerase chain reaction (PCR) assay to diagnose infections caused by Bartonella species.

Methods

Between January and April 2013 whole blood samples were collected by convenience from 151 cats (86 domiciled and 65 stray cats). The feline blood samples were subjected to a novel quantitative 5' nuclease real-time PCR (qPCR) for Bartonella species targeting the nictonamide adenine dinucleotide dehydrogenase gamma subunit ( nuoG) and conventional PCR assays targeting intergenic transcribed spacer, ribC, gltA, pap31 and rpoB, followed by sequencing and basic local alignment search tool analysis.

Results

The qPCR assay detected as few as 10 copies of plasmid per reaction. Forty-six (54.4% domiciled and 45.6% stray cats) of 151 sampled cats showed positive results in nuoG qPCR for Bartonella species. The absolute quantification of nuoG Bartonella DNA in sampled cats ranged from 1.1 × 104 to 1.3 × 104. Eighteen (39.1%) of 46 positive samples in the qPCR were also positive in conventional PCR assays. The sequencing confirmed that Bartonella henselae and Bartonella clarridgeiae circulate in cats in midwestern Brazil.

Conclusions and relevance

The present work provides details of a novel qPCR assay to diagnose infections caused by Bartonella species.
Tourism shopping and new urban entertainment
Authors: Zaidan Esmat A
Published: July 2015

This study explores shopping tourism with a special focus on the concept of luxury shopping in Dubai from the perspective of the consuming tourists. The study assesses the differences in the perceived importance of luxury shopping venues in Dubai as well as the perceived characteristics of luxury products in Dubai retail. Also the perceived advantages of Dubai as a luxury shopping destination are examined. Tourism shopping patterns are identified in this article based on the frequency of shopping and the significant differences in luxury purchasing patterns. Three main shopping groups (frequent shoppers, sometimes shoppers, and infrequent shoppers) were identified, and the study results show that there are differences among the different groups in their perception of the importance of the different shopping venues and entertainment options in Dubai. The study results also show that Dubai is perceived as a shopping heaven that has significant competitive advantages as a luxury shopping destination. Implications of the study results and recommendations for future studies are also discussed.
Is destination marketing organization microblogging in China delivering? An empirical analysis of information supply against consumer information needs
Authors: Zhang Jingru , Gui Ying , Wu Bihu , Morrison Alastair M , Li Cong
Published: July 2015

This research analyzed the travel planning information needs of Chinese consumers and compared these with the online posts by the Chinese destination marketing organizations (DMOs) on a microblog platform. An online consumer survey and a Sina Weibo content analysis were included in the research methodology. Overall, the amount of actual tourism-related information posted by DMOs was low, accounting for no more than one-third of all DMO microblog posts. The DMOs showed a preference for posting information in the basic information and destination cities categories, accounting for 76.2% of all the posts in this analysis. Mismatches were detected between the supply and demand for tourism information on microblog Web sites. It was concluded that DMOs were not delivering on the trip planning information needs of Chinese consumers.
Destination image formation process
Authors: Kim Hyangmi , Chen Joseph S
Published: July 2015

To augment the current perspective on the tourism destination image formation process, this study highlights the concept of ‘schema’, which is a mental structure of perceiving and classifying acquired information or knowledge. This study first proposes two schema-related models that illustrate the image formation process before, during, and after the tourist trip. Specifically, this study enlists five Prime Tourist Destination Schemas entailing (1) place, (2) mega event, (3) crisis, (4) self, and (5) emotion to depict the destination image formation process that is constantly modified owing to its dissimilation with new information, wherein these information sources could affect the formation of the destination image before the trip. Once the tourist visits the destination, the schemas may be altered, resulting in three different types of conditions within the tourist’s schematic fabric: congruity, moderate incongruity, and extreme incongruity. Accordingly, the resultant destination images after the trip may be labeled as an identical image, a moderately transformed image, or a largely transformed image based on experience input. Critical viewpoints in future model testing are furnished.
Exploring trends in and determinants of educational inequalities in self-rated health
Authors: Granström Fredrik , Molarius Anu , Garvin Peter , Elo Sirkka , Feldman Inna , Kristenson Margareta
Published: July 2015

Aims: Educational inequalities in self-rated health (SRH) in European welfare countries are documented, but recent trends in these inequalities are less well understood. We examined educational inequalities in SRH in different age groups, and the contribution of selected material, behavioural and psychosocial determinants from 2000 to 2008. Methods: Data were derived from cross-sectional surveys conducted in 2000, 2004 and 2008 including 37,478, 34,876 and 32,982 respondents, respectively, aged 25–75 in mid-Sweden. Inequalities were analysed by age-standardized and age-stratified rate ratios of poor SRH and age-standardized prevalence of determinants, and contribution of determinants by age-adjusted logistic regression. Results: Relative educational inequalities in SRH increased among women from 2000 (rate ratio (RR) 1.70, 95% CI 1.55–1.85) to 2008 (RR 2.07, 95% CI 1.90–2.26), but were unchanged among men (RR 1.91–2.01). The increase among women was mainly due to growing inequalities in the age group 25–34 years. In 2008, significant age differences emerged with larger inequalities in the youngest compared with the oldest age group in both genders. All determinants were more prevalent in low educational groups; the most prominent were lack of a financial buffer, smoking and low optimism. Educational differences were unchanged over the years for most determinants. In all three surveys, examined determinants together explained a substantial part of the educational inequalities in SRH. Conclusions: Increased relative educational health inequalities among women, and persisting inequalities among men, were paralleled by unchanged, large differences in material/structural, behavioural and psychosocial factors. Interventions to reduce these inequalities need to focus on early mid-life.
Object interviews, material imaginings and ‘unsettling’ methods: interdisciplinary approaches to understanding materials and material culture
Authors: Woodward Sophie
Published: July 2015

This article aims to explore the possibilities and limitations of contemporary qualitative methods for understanding materials and material culture and how these can be expanded through interdisciplinary approaches. Taking the case study of an interdisciplinary project into old jeans, the article first considers the use of object interviews and life histories to explore how people ‘speak’ the material. Second, it develops the possibilities afforded by inventive material methods, such as socio-archaeological approaches of ‘material imaginings’. Finally, the article discusses the interdisciplinary project through the dialogues that took place around the methods of design and of textile technology and the data produced. Focusing upon dialogues offers a means of exploring the tensions and also connections between methods as a site for expanding qualitative understandings of materials as ‘live’ and vibrant. It aims to widen the remit of qualitative research methods to incorporate the material.
A Narrative Approach to Women’s Lawbreaking
Authors: Fleetwood Jennifer
Published: July 2015

This article argues for the value of narrative criminology for feminist explanations of women’s lawbreaking. Contemporary theories note the significance of material gendered inequalities; however, narrative offers a way to include discursive aspects of gender. Drawing on recent developments in narrative criminology, this article analyzes how women may “talk themselves into” lawbreaking. Analysis draws on interviews with three women with diverse experiences in the drug trade and shows how drug trafficking was narrated as impossible, meaningful, and inevitable. A narrative approach therefore offers ways to understand how for some women, under some circumstances, lawbreaking may become meaningful.
Energy-saving control model of inverter for centrifugal pump systems
Authors: Luo Yin , Yuan Shouqi , Sun Hui , Guo Yihang
Published: July 2015

The inverter control strategy is the key to pump energy-saving operation and should be established based on the current system configurations and system requirements, which is not the case in practice. As a result, the characteristics of pump system requirements and a combination pump with inverter were studied, and the mathematical models were established. A new model for an optimal inverter control strategy based on the current system configurations and system requirements was then established, and a method combining golden section search and genetic algorithm was formulated to solve this optimal model. This model sets up an optimal inverter control strategy to increase the efficiency of pump operation following a process line near the minimum requirements to improve operation conditions. The implementation difficulty of the control law was also reduced. Finally, the optimized model was applied to an industrial circulating pump system, and the result showed that the model can not only determine the optimal inverter control strategy but also evaluate the current operation situation of the pump configuration and determine the energy-saving potential for the current configuration, which can aid in the subsequent energy-saving reconstruction.
A method of applying two-pump system in automatic transmissions for energy conservation
Authors: Dong Peng , Liu Yanfang , Liu Yang , Xu Xiangyang
Published: July 2015

In order to improve the hydraulic efficiency, modern automatic transmissions tend to apply electric oil pump in their hydraulic system. The electric oil pump can support the mechanical oil pump for cooling, lubrication, and maintaining the line pressure at low engine speeds. In addition, the start–stop function can be realized by means of the electric oil pump; thus, the fuel consumption can be further reduced. This article proposes a method of applying two-pump system (one electric oil pump and one mechanical oil pump) in automatic transmissions based on the forward driving simulation. A mathematical model for calculating the transmission power loss is developed. The power loss transfers to heat which requires oil flow for cooling and lubrication. A leakage model is developed to calculate the leakage of the hydraulic system. In order to satisfy the flow requirement, a flow-based control strategy for the electric oil pump is developed. Simulation results of different driving cycles show that there is a best combination of the size of electric oil pump and the size of mechanical oil pump with respect to the optimal energy conservation. Besides, the two-pump system can also satisfy the requirement of the start–stop function. This research is extremely valuable for the forward design of a two-pump system in automatic transmissions with respect to energy conservation and start–stop function.
The role of tourism in the production of cultural memory: The case of ‘Homesick Tourism’ in Poland
Authors: Marschall Sabine
Published: July 2015

Individual and collective forms of memory are driving forces behind the phenomenon of ‘homesick tourism’, the journeys undertaken by German expellees and refugees to their former homes in what is now Poland. Based on a content analysis of travel reports written by homesick tourists, this article applies concepts and theoretical approaches in the field of Memory Studies to the field of tourism, arguing that travelling can be considered an extension of the process of remembering. With reference to specific examples, it is illustrated how the encounter of ‘personal memory sites’ impacts autobiographical memory and how the activities of the homesick tourists and the transnational exchange and circulation of memory facilitated through personal contacts contributes to the emergence of new discourses about the past and ultimately the production of cultural memory.
Arginine-rich histones have strong antiviral activity for influenza A viruses
Authors: Hoeksema Marloes , Tripathi Shweta , White Mitchell , Qi Li , Taubenberger Jeffery , van Eijk Martin , Haagsman Henk , Hartshorn Kevan L
Published: July 2015

While histones are best known for DNA binding and transcription-regulating properties, they also have antimicrobial activity against a broad range of potentially pathogenic organisms. Histones are abundant in neutrophil extracellular traps, where they play an important role in NET-mediated antimicrobial killing. Here, we show anti-influenza activity of histones against both seasonal H3N2 and H1N1, but not pandemic H1N1. The arginine rich histones, H3 and H4, had greater neutralizing and viral aggregating activity than the lysine rich histones, H2A and H2B. Of all core histones, histone H4 is most potent in neutralizing IAV, and incubation with IAV with histone H4 results in a decrease in uptake and viral replication by epithelial cells when measured by qRT-PCR. The antiviral activity of histone H4 is mediated principally by direct effects on viral particles. Histone H4 binds to IAV as assessed by ELISA and co-sedimentation of H4 with IAV. H4 also induces aggregation, as assessed by confocal microscopy and light transmission assays. Despite strong antiviral activity against the seasonal IAV strains, H4 was inactive against pandemic H1N1. These findings indicate a possible role for histones in the innate immune response against IAV.
Current Emotion Research in Social Psychology: Thinking About Emotions and Other People
Authors: Parkinson Brian , Manstead Antony S. R.
Published: July 2015

This article discusses contemporary social psychological approaches to (a) the social relations and appraisals associated with specific emotions; (b) other people’s impact on appraisal processes; (c) effects of emotion on other people; and (d) interpersonal emotion regulation. We argue that single-minded cognitive perspectives restrict our understanding of interpersonal and group-related emotional processes, and that new methodologies addressing real-time interpersonal and group processes present promising opportunities for future progress.
Developing government expertise in strategic contracting for public–private partnerships
Authors: Boyer Eric J , Newcomer Kathryn E
Published: July 2015

While there is general consensus that a lack of internal skills and abilities threatens contracting performance, there is relatively little research on the processes and practices by which government develops knowledge in contract design and implementation. Drawing from primary data collected from two state government agencies in the USA, this research identifies the ways public managers use lessons from their own organization and from the wider organizational environment to improve their approach to contracting for public–private partnerships (PPPs). A four-part framework of organizational learning is presented to guide public sector capacity development for PPPs. The results suggest that public and private interests conflict not only in contract design and implementation, but also in the battle for ideas that inform government decision-making. The results also suggest that a number of internal management reforms are needed to foster a climate amenable to organizational learning on PPPs.
Evaluation of Efficacy of an Herbal Compound on Dry Mouth in Patients With Head and Neck Cancers
Authors: Ameri Ahmad , Heydarirad Ghazaleh , Rezaeizadeh Hossein , Choopani Rasool , Ghobadi Ali , Gachkar Latif
Published: July 2015

Dry mouth is a common complication of radiotherapy for head and neck cancers. This study compared the efficacy of an herbal compound containing Malva sylvestris and Alcea digitata (Boiss) with artificial saliva (Hypozalix) for improving the symptoms of dry mouth in head and neck cancer patients. The study examined a total of 62 subjects assigned to 2 groups. The herbal compound and Hypozalix were administered for 4 weeks. Efficacy was assessed using the visual analog scale and by grading the degree of dry mouth. Both groups showed a significant difference between visual analog scale before and following intervention. There was also a significant difference in visual analog scale between groups at 4 weeks after onset of intervention. The herbal group showed a significant difference between the grade of dry mouth before and after intervention, but no change was observed for grade of dry mouth in the Hypozalix group. This study supports the efficacy of the herbal compound for controlling symptoms of dry mouth in head and neck cancer patients.
Feasibility and Acceptability of Cryptococcal Antigen Screening and Prevalence of Cryptocococcemia in Patients Attending a Resource-Limited HIV/AIDS Clinic in Malawi
Authors: Chipungu Chifundo , Veltman Jennifer A. , Jansen Perry , Chiliko Peter , Lossa Christina , Namarika Dan , Benner Blake , Hoffman Risa M. , Bristow Claire C. , Klausner Jeffrey D.
Published: July 2015

Background:

The World Health Organization (WHO) recommends screening patients living with AIDS to detect and treat early cryptococcal infection.

Methods:

The authors evaluated a cryptococcal antigen (CrAg) screening and treatment program at an HIV/AIDS clinic in Malawi. Eligible patients were of age >18 years, had a CD4 count <100 cells/µL or WHO clinical HIV/AIDS stage III or IV.

Results:

Of 552 patients who presented for care, 113 were eligible, and all (100%) agreed to CrAg screening. Of them, 2 (1.8%; 95% confidence interval [CI]: 0-4.2%) patients were CrAg positive. Among those with CD4 count <100 cells/µL or WHO stage IV, the CrAg prevalence was 3.5% (95% CI: 0-8.4%) and 5.0% (95% CI: 0-15%), respectively.

Conclusion:

A CrAg screening program was acceptable to new patients in a Malawian HIV/AIDS clinic. The CrAg prevalence for patients with CD4 count < 100 cells/µL and WHO stage IV was consistent with cost-effectiveness estimates. CrAg screening and treatment programs for patients living with AIDS should be expanded.
Issues associated with welding and surfacing of large mobile mining equipment for use in oil sands applications
Authors: Barnes N. , Joseph T. , Mendez P. F.
Published: July 2015

Welding for large mobile mining equipment commonly used in the oil sands mining industry represents a unique aspect of the construction and mining heavy equipment industries. Low volume, high production capacity dominates, differing from the high volume, low production typical of the on-highway cartage automotive industry. The use of robotic welders is increasing but remains predominantly avoided due to the high cost associated with fixturing and positioning of large structural components, compounded by tolerance concerns. The main issues facing weld performance are fatigue and wear. A large portion of the ultraclass large mobile mining equipment industry focuses on fast field repair techniques, dominated by shielded metal arc welding, while in shop repairs, gas metal arc welding remains the preference.
Effect of stress on precipitation behaviour of 7xxx alloy during age forming process
Authors: Chen J. F. , Zou L. C. , Chen Y. L. , Li Q.
Published: July 2015

In the present paper, the effect of stress on precipitation behaviour, which decides the strength of 7xxx alloy, has been investigated through a comparative analysis of the difference in precipitation behaviour in 7050 alloy treated by age forming and traditional aging. The results suggest that the stress can enhance precipitate nucleation and growth in age forming, which mainly attributes to two reasons. First, the increased diffusion coefficient caused by applied stress field in age forming induces precipitates to growth. Second, in age forming, obvious dislocation movement caused by initial stress supplied short circuit diffusion passway and nucleation interface is of benefit to the precipitate nucleation and growth. Besides, the promoting precipitation effect decays gradually with stress relaxation during the age forming process.
The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell–based immunotherapy
Authors: Walz Simon , Stickel Juliane S. , Kowalewski Daniel Johannes , Schuster Heiko , Weisel Katja , Backert Linus , Kahn Stefan , Nelde Annika , Stroh Tatjana , Handel Martin , Kohlbacher Oliver , Kanz Lothar , Salih Helmut Rainer , Rammensee Hans-Georg , Stevanović Stefan
Published: July 2015

Key Points

Direct analysis of the HLA-presented peptidome identifies a distinct antigenic signature in MM. T-cell responses for these antigens are detectable exclusively in MM patients and can be induced in vitro in response-naive patients.
Performance of urine lipoarabinomannan assays for paediatric tuberculosis in Tanzania
Authors: Kroidl Inge , Clowes Petra , Reither Klaus , Mtafya Bariki , Rojas-Ponce Gabriel , Ntinginya Elias N. , Kalomo Mariam , Minja Lilian T. , Kowuor Dickens , Saathoff Elmar , Kroidl Arne , Heinrich Norbert , Maboko Leonard , Bates Matthew , O'Grady Justin , Zumla Alimuddin , Hoelscher Michael , Rachow Andrea
Published: July 2015

We evaluated the diagnostic performance of two tests based on the release of lipoarabinomannan (LAM) into the urine, the MTB-LAM-ELISA assay and the Determine TB-LAM-strip assay, in children with suspected tuberculosis (TB) in a high TB/HIV-prevalence setting.

In a prospective study, 132 children with suspected active TB were assigned to diagnostic subgroups. Urine samples were subjected to testing by both assays to ascertain sensitivity and specificity. Host factors associated with positive LAM results were investigated and LAM excretion monitored after antituberculous treatment initiation.

18 (13.6%) children had culture-confirmed pulmonary TB. The assays' sensitivity was higher in HIV-positiveversusHIV-negative children: 70% (95% confidence interval 35–93%)versus13% (0–53%) for MTB-LAM-ELISA and 50% (19–81%)versus0% (0–37%) for Determine TB-LAM. In 35 (27%) children with excluded active TB, both assays showed a specificity of 97.1% (85–100%). Proteinuria and low body mass index were independently associated with LAM positivity. In most patients, LAM excretion declined to zero during or at conclusion of antituberculous treatment.

HIV/TB co-infected children might benefit from LAM-based tests to aid early TB diagnosis and subsequent positive impact on morbidity and mortality. Using LAM as a rule-in and treatment-monitoring tool may also show further potential.
Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure
Authors: Verleden Stijn E. , Vasilescu Dragoş M. , McDonough John E. , Ruttens David , Vos Robin , Vandermeulen Elly , Bellon Hannelore , Geenens Rachel , Verbeken Erik K. , Verschakelen Johny , Van Raemdonck Dirk E. , Wuyts Wim A. , Sokolow Youri , Knoop Christiane , Cooper Joel D. , Hogg James C. , Verleden Geert M. , Vanaudenaerde Bart M.
Published: July 2015

Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients receiving a redo-transplant as treatment for CLAD.

Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were air-inflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology.

The MDCT showed reduced lung volume with increased lung weight and density in RASversusBOS and control (p<0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles (p<0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls (p<0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue.

RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue.
Biomarkers to identify sputum eosinophilia in different adult asthma phenotypes
Authors: Westerhof Guus A. , Korevaar Daniël A. , Amelink Marijke , de Nijs Selma B. , de Groot Jantina C. , Wang Junfeng , Weersink Els J. , ten Brinke Anneke , Bossuyt Patrick M. , Bel Elisabeth H.
Published: July 2015

Several biomarkers have been used to assess sputum eosinophilia in asthma. It has been suggested that the diagnostic accuracy of these biomarkers might differ between asthma phenotypes. We investigated the accuracy of biomarkers in detecting sputum eosinophilia (≥3%) in different adult asthma phenotypes.

Levels of eosinophils in blood and sputum, exhaled nitric oxide fraction (FeNO) and total immunoglobulin (Ig)E from 336 adult patients, enrolled in three prospective observational clinical trials and recruited at five pulmonology outpatient departments, were analysed. Areas under the receiver operating characteristics curves (AUC) for detecting sputum eosinophilia were calculated and compared between severe and mild, obese and nonobese, atopic and nonatopic and (ex-)smoking and never-smoking asthma patients.

Sputum eosinophilia was present in 116 patients (35%). In the total group the AUC was 0.83 (95% CI 0.78–0.87) for blood eosinophils, 0.82 (0.77–0.87) forFeNOand 0.69 (0.63–0.75) for total IgE. AUCs were similar for blood eosinophils andFeNObetween different phenotypes. Total IgE was less accurate in detecting sputum eosinophilia in atopic and obese patients than in nonatopic and nonobese patients.

Blood eosinophils andFeNOhad comparable diagnostic accuracy (superior to total IgE) in identifying sputum eosinophilia in adult asthma patients, irrespective of asthma phenotype such as severe, nonatopic, obese and smoking-related asthma.
Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis
Authors: Kosanovic Djuro , Luitel Himal , Dahal Bhola Kumar , Cornitescu Teodora , Janssen Wiebke , Danser A.H. Jan , Garrelds Ingrid M. , De Mey Jo G.R. , Fazzi Gregorio , Schiffers Paul , Iglarz Marc , Fischli Walter , Ghofrani Hossein Ardeschir , Weissmann Norbert , Grimminger Friedrich , Seeger Werner , Reiss Irwin , Schermuly Ralph Theo
Published: July 2015

Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.

The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.

Chymase inhibition resulted in attenuation of pulmonary hypertension and pulmonary fibrosis, as evident from improved haemodynamics, decreased right ventricular remodelling/hypertrophy, pulmonary vascular remodelling and lung fibrosis. These beneficial effects were associated with a strong tendency of reduction in mast cell number and activity, and significantly diminished chymase expression levels. Mechanistically, chymase inhibition led to attenuation of transforming growth factor β1 and matrix-metalloproteinase-2 contents in the lungs. Furthermore, chymase inhibition prevented big endothelin-1-induced vasoconstriction of the pulmonary arteries.

Therefore, chymase plays a role in the pathogenesis of pulmonary hypertension associated with pulmonary fibrosis and may represent a promising therapeutic target. In addition, this study may provide valuable insights on the contribution of chymase in the pulmonary hypertension context, in general, regardless of the pulmonary hypertension form.
Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice
Authors: Morissette Mathieu C. , Shen Pamela , Thayaparan Danya , Stämpfli Martin R.
Published: July 2015

Overwhelming evidence links inflammation to the pathogenesis of smoking-related pulmonary diseases, especially chronic obstructive pulmonary disease (COPD). Despite an increased understanding of the disease pathogenesis, mechanisms initiating smoking-induced inflammatory processes remain incompletely understood.

To investigate the mechanisms that initiate and propagate smoke-induced inflammation, we used a well-characterised mouse model of cigarette smoke exposure, mice deficient for interleukin (IL)-1α, IL-1β and Toll-like receptor 4, and antibodies blocking granulocyte-macrophage colony-stimulating factor (GM-CSF). Studies were also pursued using intranasal delivery of human oxidised low-density lipoprotein (hOxLDL), a source of oxidised lipids, to investigate the inflammatory processes associated with impaired lipid homeostasis.

We found that cigarette smoke exposure rapidly led to lipid accumulation in pulmonary macrophages, a defining feature of foam cells, which in turn released high levels of IL-1α. In smoke-exposed IL-1α-deficient mice, phospholipids accumulated in the bronchoalveolar lavage, a phenomenon also observed when blocking GM-CSF. Intranasal administration of hOxLDL led to lipid accumulation in macrophages and initiated an inflammatory process that mirrored the characteristics of cigarette smoke-induced inflammation.

These findings identify a link between lipid accumulation in macrophages, inflammation and damaged surfactant, suggesting that the response to damaged pulmonary surfactant is a central mechanism that drives cigarette smoke-induced inflammation. Further investigations are required to explore the role of distorted lipid homeostasis in the pathogenesis of COPD.
ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax
Authors: Tschopp Jean-Marie , Bintcliffe Oliver , Astoul Philippe , Canalis Emilio , Driesen Peter , Janssen Julius , Krasnik Marc , Maskell Nicholas , Van Schil Paul , Tonia Thomy , Waller David A. , Marquette Charles-Hugo , Cardillo Giuseppe
Published: July 2015

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research.

The European Respiratory Society's Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence.

Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach.

In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required.
Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension
Authors: McLaughlin Vallerie , Channick Richard N. , Ghofrani Hossein-Ardeschir , Lemarié Jean-Christophe , Naeije Robert , Packer Milton , Souza Rogério , Tapson Victor F. , Tolson Jonathan , Al Hiti Hikmet , Meyer Gisela , Hoeper Marius M.
Published: July 2015

The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated.

In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (≥20 mg three times daily) for ≥3 months were randomised (1:1) to placebo or bosentan (125 mg twice daily). The composite primary end-point was the time to the first morbidity/mortality event, defined as all-cause death, hospitalisation for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or PAH worsening. Secondary/exploratory end-points included change in 6-min walk distance and World Health Organization functional class at 16 weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death.

Overall, 334 PAH patients were randomised to placebo (n=175) or bosentan (n=159). A primary end-point event occurred in 51.4% of patients randomised to placebo and 42.8% to bosentan (hazard ratio 0.83, 97.31% CI 0.58–1.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16 weeks was +21.8 m (95% CI +5.9–37.8 m; p=0.0106). Except for NT-proBNP, no difference was observed for any other end-point. The safety profile of bosentan added to sildenafil was consistent with the known bosentan safety profile.

In COMPASS-2, adding bosentan to stable sildenafil therapy was not superior to sildenafil monotherapy in delaying the time to the first morbidity/mortality event.
The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle
Authors: Manders Emmy , Rain Silvia , Bogaard Harm-Jan , Handoko M. Louis , Stienen Ger J.M. , Vonk-Noordegraaf Anton , Ottenheijm Coen A.C. , de Man Frances S.
Published: July 2015

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction.
Prospective participant selection and ranking to maximize actionable pharmacogenetic variants and discovery in the eMERGE Network
Authors: Crosslin David R. , Robertson Peggy D. , Carrell David S. , Gordon Adam S. , Hanna David S. , Burt Amber , Fullerton Stephanie M. , Scrol Aaron , Ralston James , Leppig Kathleen , Hartzler Andrea , Baldwin Eric , Andrade Mariza de , Kullo Iftikhar J. , Tromp Gerard , Doheny Kimberly F. , Ritchie Marylyn D. , Crane Paul K. , Nickerson Deborah A. , Larson Eric B. , Jarvik Gail P.
Published: July 2015

Background

In an effort to return actionable results from variant data to electronic health records (EHRs), participants in the Electronic Medical Records and Genomics (eMERGE) Network are being sequenced with the targeted Pharmacogenomics Research Network sequence platform (PGRNseq). This cost-effective, highly-scalable, and highly-accurate platform was created to explore rare variation in 84 key pharmacogenetic genes with strong drug phenotype associations.

Methods

To return Clinical Laboratory Improvement Amendments (CLIA) results to our participants at the Group Health Cooperative, we sequenced the DNA of 900 participants (61 % female) with non-CLIA biobanked samples. We then selected 450 of those to be re-consented, to redraw blood, and ultimately to validate CLIA variants in anticipation of returning the results to the participant and EHR. These 450 were selected using an algorithm we designed to harness data from self-reported race, diagnosis and procedure codes, medical notes, laboratory results, and variant-level bioinformatics to ensure selection of an informative sample. We annotated the multi-sample variant call format by a combination of SeattleSeq and SnpEff tools, with additional custom variables including evidence from ClinVar, OMIM, HGMD, and prior clinical associations.

Results

We focused our analyses on 27 actionable genes, largely driven by the Clinical Pharmacogenetics Implementation Consortium. We derived a ranking system based on the total number of coding variants per participant (75.2±14.7), and the number of coding variants with high or moderate impact (11.5±3.9). Notably, we identified 11 stop-gained (1 %) and 519 missense (20 %) variants out of a total of 1785 in these 27 genes. Finally, we prioritized variants to be returned to the EHR with prior clinical evidence of pathogenicity or annotated as stop-gain for the following genes: CACNA1S and RYR1 (malignant hyperthermia); SCN5A, KCNH2, and RYR2 (arrhythmia); and LDLR (high cholesterol).

Conclusions

The incorporation of genetics into the EHR for clinical decision support is a complex undertaking for many reasons including lack of prior consent for return of results, lack of biospecimens collected in a CLIA environment, and EHR integration. Our study design accounts for these hurdles and is an example of a pilot system that can be utilized before expanding to an entire health system.
Use of Feedback-Oriented Online Exercises to Help Physiology Students Construct Well-Organized Answers to Short-Answer Questions
Authors: Carnegie Jacqueline
Published: July 2015

Postsecondary education often requires students to use higher-order cognitive skills (HOCS) such as analysis, evaluation, and creation as they assess situations and apply what they have learned during lecture to the formulation of solutions. Summative assessment of these abilities is often accomplished using short-answer questions (SAQs). Quandary was used to create feedback-oriented interactive online exercises to help students strengthen certain HOCS as they actively constructed answers to questions concerning the regulation of 1) metabolic rate, 2) blood sugar, 3) erythropoiesis, and 4) stroke volume. Each exercise began with a SAQ presenting an endocrine dysfunction or a physiological challenge; students were prompted to answer between six and eight multiple-choice questions while building their answer to the SAQ. Student outcomes on the SAQ sections of summative exams were compared before and after the introduction of the online tool and also between subgroups of students within the posttool-introduction population who demonstrated different levels of participation in the online exercises. While overall SAQ outcomes were not different before and after the introduction of the online exercises, once the SAQ tool had become available, those students who chose to use it had improved SAQ outcomes compared with those who did not.