bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review
Authors: Alonso MD , Martinez-Vazquez F , de Teran T Diaz , Miranda-Filloy JA , Dierssen T , Blanco R , Gonzalez-Juanatey C , Llorca J , Gonzalez-Gay MA
Published: June 2012

To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1–5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6–2.2] per 100,000 population) ( p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE ( p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies, late-onset SLE patients from NW Spain have some clinical and laboratory differences with respect to those individuals with early-onset SLE. Our data support the claim of a reduced probability of survival in the older age-group of SLE patients.
Treatment Outcome of Multidrug-Resistant Mycobacterium tuberculosis in Nepal
Authors: Kakchapati Sampurna , Gyawali Badri Nath , Jha Rakesh Kumar , Choonpradub Chamnein
Published: June 2012

The purpose of this study was to examine factors associated with treatment outcome of multidrug-resistant tuberculosis (MDR-TB) cases in Nepal. A retrospective analysis of MDR-TB cases by demographic determinants and treatment was conducted. A total of 494 MDR-TB cases were registered from 2005 to 2008, with data obtained from the National Tuberculosis Center. Chi-squared tests were used to assess statistically the association between smear and culture conversion and treatment outcome. Determinants were analyzed with the use of Kaplan–Meier curves and Cox proportional hazards models to generate estimates of the associations with the time to treatment outcome. Sputum conversion status and culture conversion status were positively associated with treatment outcome for MDR-TB. In a multiple Cox proportional hazards regression model, no determinants were found to be associated with time to cure.
Cervical and Anal Human Papillomavirus Infection in Adult Women in American Samoa
Authors: Hernandez Brenda Y. , Ka’opua Lana S. , Scanlan Luana , Ching John Ah , Kamemoto Lori E. , Thompson Pamela J. , Zhu Xuemei , Shvetsov Yurii B. , Tofaeono Jennifer , Williams Victor Tofaeono
Published: June 2012

The prevalence of cervical and anal human papillomavirus (HPV) and risk factors associated with infections were evaluated in a cross-sectional study of 211 adult women in American Samoa. Overall, 53% of women reported ever having a Pap smear. Cervical and anal HPV was detected in 10% and 16% of women, respectively; 4% of women had concurrent cervical and anal HPV. The most common cervical genotypes were HPV 6, HPV 16, and HPV 53. Cutaneous HPV types were detected in 40% of anal infections. Cervical HPV infection was associated with anal HPV (age-adjusted odds ratio = 3.32, 1.10-10.00). After age adjustment, cervical HPV was associated with being unmarried, postsecondary education, hot running water at home, multiple sexual partners, nulliparity, condom use, and other contraceptive methods. In multivariate analyses, only age remained associated with cervical HPV and anal HPV. Cervical and anal HPV was more prevalent among younger women; only anal HPV was detected in older women.
Maternal Autonomy and Child Health Care Utilization in India
Authors: Malhotra Chetna , Malhotra Rahul , Østbye Truls , Subramanian S. V.
Published: June 2012

The objective of this study was to examine the association of maternal autonomy with preventive and curative child health care utilization in India. Data from the National Family Health Survey 2005-2006 were used to ascertain association of maternal autonomy (in 3 dimensions: decision making, access to financial resources, freedom of movement) with child’s primary immunization status (indicative of preventive health care use) and treatment seeking for child’s acute respiratory infection (indicative of curative health care use). Low maternal freedom of movement was associated with higher odds of incomplete primary immunization of the child and for not seeking treatment for the child’s acute respiratory infection. Low maternal financial access was associated with increased odds for incomplete primary immunization of the child. The findings show that improvement in autonomy of Indian mothers, especially their freedom of movement, may help improve utilization of health care for their children.
Growth Curves for School Children From Kuching, Sarawak
Authors: Bong Yii Bonn , Shariff Asma Ahmad , Mohamed Abdul Majid , Merican Amir Feisal
Published: June 2012

In this article, the authors propose reference curves for height and weight for school children in the Kuching area, Sarawak. The school children were from primary to secondary schools (aged 6.5 to 17 years old) and comprised both genders. Anthropometric measurements and demographic information for 3081 school-aged children were collected (1440 boys and 1641 girls). Fitted line plots and percentiles for height and weight (3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles) were obtained. The height of school boys and school girls were almost similar at the start of their school-going age. For school girls, height and weight values stabilized when they reached 16 or 17 years old but kept increasing for school boys. School boys were taller than school girls as they entered adolescence. Height differences between school boys and school girls became significantly wider as they grew older. Chinese school children were taller and heavier than those of other ethnic groups.
Equity of Access Under Korean Universal Health Insurance
Authors: Park Ju Moon
Published: June 2012

This study examined the extent to which equity in the use of physician services has been achieved in the Republic of Korea. Descriptive and logistic regression analysis was performed examining the relationship between the dependent variable and the independent variables and the relative importance of factors. The results indicate that a universal health insurance system has not yielded a fully equitable distribution of services. Access differences arise from coverage limitation, as well as urban/rural variations in the distributions of providers. The policy options for expansion of coverage should be encouraged to ease the financial burden of out-of-pocket payments on patients and to limit the range of noninsured services. Urban/rural variations in the distributions of providers are caused by the government’s “laissez-faire” policy for the private medical sector. To solve this geographic misdistribution, the attention of policy makers is required, with changing of the government’s “laissez-faire” policy.
The Alcohol Dehydrogenase 1C(rs698) Genotype and Breast Cancer
Authors: Mao Qunxia , Gao Linggen , Wang Hongwei , Wang Qian , Zhang Tong
Published: June 2012

Published data regarding the association between alcohol dehydrogenase (ADH) 1C genotypes and breast cancer risk show conflicting results. The authors performed this meta-analysis on 1969 patients and 2244 controls from 4 (including 7 study populations) related case-control studies to estimate the association between ADH1C(rs698) genotyping information and breast cancer risk. According to the 6 eligible populations, the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk for ADH1C 1-2 versus ADH1C 2-2, ADH1C 1-1 versus ADH1C 2-2 genotype, and ADH1C 1 versus ADH1C 2 were 1.16 (0.95-1.42), 1.17 (0.95-1.44), and 1.05 (0.96-1.16), respectively. The OR (95% CI) for ADH1C 1-1 + ADH1C 1-2 versus ADH1C 2-2 from the 7 study populations was 1.14 (0.96-1.36). Meanwhile, genotypes of ADH1C 1-1 + ADH1C 1-2 increased the risk of breast cancer in drinkers (OR = 1.35; 95% CI = 1.03-1.76). This meta-analysis suggested that the ADH1C 1 allele might modestly influence the effect of alcohol on breast cancer but is not an independent risk factor for breast cancer. However, more restricted prospective studies are needed.
Validity of the Malay Version of the Internet Addiction Test
Authors: Chong Guan Ng , Isa Saramah Mohammed , Hashim Aili Hanim , Pillai Subash Kumar , Harbajan Singh Manveen Kaur
Published: June 2012

The use of the Internet has been increasing dramatically over the decade in Malaysia. Excessive usage of the Internet has lead to a phenomenon called Internet addiction. There is a need for a reliable, valid, and simple-to-use scale to measure Internet addiction in the Malaysian population for clinical practice and research purposes. The aim of this study was to validate the Malay version of the Internet Addiction Test, using a sample of 162 medical students. The instrument displayed good internal consistency (Cronbach’s α = .91), parallel reliability (intraclass coefficient = .88, P < .001), and concurrent validity with the Compulsive Internet Use Scale (Pearson’s correlation = .84, P < .001). Receiver operating characteristic analysis showed that 43 was the optimal cutoff score to discriminate students with and without Internet dependence. Principal component analysis with varimax rotation identified a 5-factor model. The Malay version of the Internet Addiction Test appeared to be a valid instrument for assessing Internet addiction in Malaysian university students.
U.S. Students Study Abroad in the Middle East/North Africa
Authors: Lane-Toomey Cara K. , Lane Shannon R.
Published: June 2012

The political events of the last decade and the Arab Spring have made it more important than ever for Americans to understand the language, culture, and history of the Middle East/North Africa (MENA) region. Study abroad is one important method that can significantly increase American students’ understanding of the Arabic language and the culture of MENA. During the past decade, the number of U.S. undergraduate students in the MENA region has increased dramatically, but there is still a great need for growth and understanding in this area. This research analyzes data from a cross-sectional survey and focus groups of U.S. undergraduate study abroad students to investigate the motivations, attitudes, and aspects of human capital that influence study abroad destination choice. These findings provide insight for policy makers, faculty, and international educators who want to expand students’ options for study abroad and for students who are considering whether this avenue is right for them.
Examination of small crack normal to multiple elasticity and plasticity mismatched interfaces in residually stressed fiber metal laminate (Glare): Theoretical and numerical approaches
Authors: Bhat Sunil , Patibandla Rajasekhar
Published: June 2012

A small Mode I crack, normal to interfaces between elasticity and plasticity mismatched material layers, in a residually stressed aluminum–fiber laminate (Glare) is modeled under monotonic and cyclic loads. An analytical model is presented in small scale yielding or K-dominant regime that quantifies the effect of property mismatched interfaces over the crack tip in the laminate by determining energy release rate and stress intensity parameter. Cracked laminate is also modeled by finite element method. Values of energy release rate and strain energy density are obtained over cyclic paths far away from the crack tip, around the influencing interfaces, and in the vicinity of the crack tip. Numerical results are found to be close to theoretical estimations. Re-distribution of stress state in un-identical material layers during crack growth, resulting in different energy release rates of the crack in the laminate vis-a-vis those of the crack in similarly stressed homogeneous aluminum, is well substantiated. Methodology to incorporate the surface and material micro-structural effects over the crack is also proposed.
How the Early Voltage Clamp Studies of José del Castillo Inform “Modern” Neuroscience
Authors: Zottoli Steven J.
Published: June 2012

The description of ionic currents that flow across the membrane of the squid giant axon during an action potential sparked an interest in determining whether there were similar currents in vertebrates. The preparation of choice was the node of Ranvier in single myelinated fibers in frog. José del Castillo spent 3 years on the United States mainland from 1956 to 1959. During that time, he collaborated with Jerome Y. Lettvin and John W. Moore. I discuss how these individuals met one another and some of their scientific discoveries using the voltage clamp to study squid giant axons and frog nodes. Much of this work was conducted at the Marine Biological Laboratory in Woods Hole, MA, and I attempt to convey a sense of the unique scientific “melting pot” that existed at the Marine Biological Laboratory and the broader effect that del Castillo had on “modern” neuroscience.
Intracranial EEG Surface Renderings
Authors: Youngblood Mark W. , Han Xiao , Farooque Pue , Jhun Stephen , Bai Xiaoxiao , Yoo Ji Yeoun , Lee Hyang Woon , Blumenfeld Hal
Published: June 2012

Intracranial electro-encephalography (icEEG) provides a unique opportunity to record directly from the human brain and is clinically important for planning epilepsy surgery. However, traditional visual analysis of icEEG is often challenging. The typical simultaneous display of multiple electrode channels can prevent an in-depth understanding of the spatial-time course of brain activity. In recent decades, advances in the field of neuroimaging have provided powerful new tools for the analysis and display of signals in the brain. These methods can now be applied to icEEG to map electrical signal information onto a three-dimensional rendering of a patient’s cortex and graphically observe the changes in voltage over time. This approach provides rapid visualization of seizures and normal activity propagating over the brain surface and can also illustrate subtle changes that might be missed by traditional icEEG analysis. In addition, the direct mapping of signal information onto accurate anatomical structures can assist in the precise targeting of sites for epilepsy surgery and help correlate electrical activity with behavior. Bringing icEEG data into a standardized anatomical space will also enable neuroimaging methods of statistical analysis to be applied. As new technologies lead to a dramatic increase in the rate of data acquisition, these novel visualization and analysis techniques will play an important role in processing the valuable information obtained through icEEG.
Robust fault detection filter using linear matrix inequalities’ approach for shaft crack diagnosis
Authors: Kulesza Zbigniew , Sawicki Jerzy T , Gyekenyesi Andrew L
Published: June 2012

Detecting cracks in rotating shafts is a challenging problem when using vibration-based diagnostics. This is due to the fact that a localized crack has a minimal influence on the global vibration response of the system. To increase sensitivity and reliability, the vibration response needs to be coupled with additional sources of information such as a mathematical model of the machine. Modern control theory techniques offer system-level mathematical models for both control and diagnostics. Focusing on the latter, a new and promising approach involves the use of unknown input observers. Such observers can be designed to employ robust fault detection filters (RFDFs) for isolating fault signatures while reducing the influence of real-world disturbances and noise. For the present study, a modified design procedure coupled with robust fault detection is utilized for shaft crack detection. The filter is designed using the linear matrix inequalities (LMI) technique. The LMI approach is applied to obtain the solution of the mixed H−/ H∞ optimization problem, which arises during the synthesis of the RFDF. By reformulating the LMI conditions, the proposed RFDF design procedure is simplified and thus requires less iteration steps to find the optimal solution. A new feature of the present approach involves the application of the rigid finite element method for the formulation of the mathematical model of the rotor and the shaft crack. The numerical and experimental results confirm the advantages of the designed robust fault detection filter and its ability to detect shaft cracks. The filter is minimally sensitive to measurement noise while allowing for the identification of shallow cracks (2% or 5% deep). The cracks are manifested through the observance of very subtle vibration response changes. The results also confirm the effectiveness and accuracy of the rigid finite element modeling concerning the cracked rotor.
Alcohol and Substance Use History Among ADHD Adults
Authors: Huntley Zoe , Young Susan
Published: June 2012

Objective: To profile substance use, personality, service use, and employment in adults with ADHD. Method: The sample consisted of 216 consecutive referrals to an adult ADHD service and classified with ADHD, partially or fully remitted ADHD, or no ADHD. Normal controls ( n = 33) were recruited from a general practitioner’s center. Participants completed measures of alcohol and illicit substance use, employment, service use, ADHD symptoms, and personality. Results: High rates of substance use were found in participants with current ADHD diagnoses. ADHD participants showed increased rates of personality trait or disorder scores and unemployment. There was some indication that those with ADHD and substance-related impairment place higher demand on services. Individuals with partially remitted ADHD showed similar substance use to those with current ADHD, whereas those in full remission were comparable with normal controls. Conclusion: Although ADHD symptoms may remit with time, individuals retaining persisting or partial symptoms have substantial needs in adulthood.
Tax and Expenditure Limitations and State Credit Ratings
Authors: Stallmann Judith I. , Deller Steven , Amiel Lindsay , Maher Craig
Published: June 2012

The impact of state tax and expenditure limitations (TELs) on bond credit ratings is estimated using an incomplete (or unbalanced) panel from the US states from 1973 to 2005. Three indices of the restrictiveness of TELs are used. Both Moody’s and Standard and Poor’s bond credit ratings are used and the outcomes compared. The results are consistent with previous work; more restrictive revenue TELs are associated with lower credit ratings while expenditure TELs are generally associated with higher credit ratings. TELs restricting both revenues and expenditures are negatively associated with Moody’ ratings, but not with those of Standard and Poor’s. Contrary to previous studies, the authors find limited differences in the fiscal and economic variables that influence the ratings of the two agencies.
Cross-cultural adaptation and validation of the Peripheral Artery Questionnaire: Korean version for patients with peripheral vascular diseases
Authors: Lee Ji Hyun , Cho Kyoung Im , Spertus John , Kim Seong Man
Published: June 2012

The Peripheral Artery Questionnaire (PAQ), as developed in US English, is a validated scale to evaluate the health status of patients with peripheral artery disease (PAD). The aim of this study was to translate the PAQ into Korean and to evaluate its reliability and validity. A multi-step process of forward-translation, reconciliation, consultation with the developer, back-translation and proofreading was conducted. The test–retest reliability was evaluated at a 2-week interval using the intra-class correlation coefficient (ICC). The validity was assessed by identifying associations between Korean PAQ (KPAQ) scores and Korean Health Assessment Questionnaire (KHAQ) scores. A total of 100 PAD patients were enrolled: 63 without and 37 with severe claudication. The reliability of the KPAQ was adequate, with an ICC of 0.71. There were strong correlations between KPAQ’s subscales. Cronbach’s alpha for the summary score was 0.94, indicating good internal consistency and congruence with the original US version. The validity was supported by a significant correlation between the total KHAQ score and KPAQ physical function, stability, symptom, social limitation and quality of life scores ( r = -0.24 to -0.90; p < 0.001) as well as between the KHAQ walking subscale and the KPAQ physical function score ( r = −0.55, p < 0.001). Our results indicate that the KPAQ is a reliable, valid instrument to evaluate the health status of Korean patients with PAD.
Polynesians and the seductive power of common sense
Authors: Terrell John Edward
Published: June 2012

Common sense and science alike are grounded in human experience. Yet these complementary perspectives on the world and our place in it are often in conflict. The contentious issue of global warming shows that when this happens, the seductive simplicity of most down-to-earth commonsense explanations can make it difficult for experts to win people over to the complexity and uncertainties of most scientific arguments. But sometimes scientists, too, succumb to the appeal of commonsense simplicity when they should not. As Fredrik Barth remarked, practically all social science reasoning rests on the premise that there are discrete groups of people that can be variously labeled ethnic groups, populations, societies, or cultures – a commonsense idea that begs more questions than it resolves. Consider the case of the so-called Polynesians of the South Seas. Scholars have been accepting for centuries the claim that these islanders collectively comprise a biological and cultural people, or race, apart from other islanders in Oceania whose ancestors migrated long ago swiftly out into the Pacific more or less already recognizably ‘Polynesian’ in their appearance, ways of speaking, and cultural practices from a homeland somewhere in Southeast Asia or on Formosa (Taiwan). Mounting convincing evidence to the contrary that can be widely accepted as defying such commonsense thinking has been and remains one of the greatest challenges to Pacific Island studies in the 21st century.
Chronic pain as a narratological distress: a phenomenological study
Authors: Lavie-Ajayi Maya , Almog Nitsan , Krumer-Nevo Michal
Published: June 2012

Objectives: This paper reports finding from a study that focused on people living with chronic pain, chronicling their experiences of pain and emotional distress, and their social and personal narratives.

Methods: The paper presents an interpretative phenomenological analysis (IPA) of six interviews conducted with men and women aged between 27 and 61. The interviews were taken from a larger study of the experience of chronic pain.

Findings: Chronic pain is a double faced phenomenon: a vivid and total experience on one hand, an elusive and deceptive phenomenon on the other. The nature of this phenomenon – together with the medical and public discourse that ignores and delegitimizes chronic pain this condition – prompts people to question their own experiences and to face what we define as a narratological distress.

Discussion: Narratological distress is the internal battle between two unwanted narratives: The elusive delegitimizing narrative of denial, which seeks to ignore the experience of pain; and the narrative that acknowledges the pain, but with the price of accepting oneself as “ill” or “disabled.”
Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of β3 integrins
Authors: Cho Jaehyung , Kennedy Daniel R. , Lin Lin , Huang Mingdong , Merrill-Skoloff Glenn , Furie Barbara C. , Furie Bruce
Published: June 2012

Extracellular protein disulfide isomerase (PDI) is required for platelet thrombus formation and fibrin generation after arteriolar wall injury in live mice. PDI is secreted from platelets and endothelial cells on cellular activation, but the mechanism of capture of secreted PDI within the injured vasculature is unknown. We establish that, like the endothelial β3 integrin αVβ3, the platelet integrin αIIbβ3 binds PDI. PDI also binds to recombinant β3. Using intravital microscopy, we demonstrate that PDI accumulation at the site of laser-induced arteriolar wall injury is markedly reduced in β3-null (β3−/−) mice, and neither a platelet thrombus nor fibrin is generated at the vessel injury site. The absence of fibrin after vascular injury in β3−/− mice is because of the absence of extracellular PDI. To evaluate the relative importance of endothelial αVβ3 versus platelet αIIbβ3 or αVβ3, we performed reciprocal bone marrow transplants on wild-type and β3−/− mice. PDI accumulation and platelet thrombus formation were markedly decreased after vessel injury in wild-type mice transplanted with β3−/− bone marrow or in β3−/− mice transplanted with wild-type bone marrow. These results indicate that both endothelial and platelet β3 integrins contribute to extracellular PDI binding at the vascular injury site.
FANCL ubiquitinates β-catenin and enhances its nuclear function
Authors: Dao Kim-Hien T. , Rotelli Michael D. , Petersen Curtis L. , Kaech Stefanie , Nelson Whitney D. , Yates Jane E. , Hanlon Newell Amy E. , Olson Susan B. , Druker Brian J. , Bagby Grover C.
Published: June 2012

Bone marrow failure is a nearly universal complication of Fanconi anemia. The proteins encoded by FANC genes are involved in DNA damage responses through the formation of a multisubunit nuclear complex that facilitates the E3 ubiquitin ligase activity of FANCL. However, it is not known whether loss of E3 ubiquitin ligase activity accounts for the hematopoietic stem cell defects characteristic of Fanconi anemia. Here we provide evidence that FANCL increases the activity and expression of β-catenin, a key pluripotency factor in hematopoietic stem cells. We show that FANCL ubiquitinates β-catenin with atypical ubiquitin chain extension known to have nonproteolytic functions. Specifically, β-catenin modified with lysine-11 ubiquitin chain extension efficiently activates a lymphocyte enhancer-binding factor-T cell factor reporter. We also show that FANCL-deficient cells display diminished capacity to activate β-catenin leading to reduced transcription of Wnt-responsive targets c-Myc and Cyclin D1. Suppression of FANCL expression in normal human CD34+ stem and progenitor cells results in fewer β-catenin active cells and inhibits expansion of multilineage progenitors. Together, these results suggest that diminished Wnt/β-catenin signaling may be an underlying molecular defect in FANCL-deficient hematopoietic stem cells leading to their accelerated loss.
General and abdominal obesity and incident asthma in adults: the HUNT study
Authors: Brumpton Ben , Langhammer Arnulf , Romundstad Pål , Chen Yue , Mai Xiao-Mei
Published: June 2012

Measures of body mass index (BMI) and waist circumference define general obesity and abdominal obesity respectively. While high BMI has been established as a risk factor for asthma in adults, waist circumference has seldom been investigated.

To determine the association between BMI, waist circumference and incident asthma in adults, we conducted a prospective study (n=23,245) in a population living in Nord-Trøndelag, Norway in 1995–2008.

Baseline BMI and waist circumference were measured and categorised as general obesity (BMI ≥30.0 kg·m2) and abdominal obesity (waist circumference ≥88 cm in females and ≥102 cm in males). Incident asthma was self-reported new-onset cases during an 11-yr follow-up period. Odds ratios for asthma associated with obesity were calculated using multivariable logistic regression.

General obesity was a risk factor for asthma in females (OR 1.96, 95% CI 1.52–2.52) and males (OR 1.84, 95% CI 1.30–2.59). In females, after additional adjustment for BMI, abdominal obesity remained a risk factor for asthma development (OR 1.46, 95% CI 1.04–2.05). Abdominal obesity seems to increase the risk of incident asthma in females in addition to BMI, indicating that using both measures of BMI and waist circumference in females may be a superior clinical assessment for asthma risk than any measure alone.
Lung function from infancy to preschool in a cohort of children with cystic fibrosis
Authors: Brumback Lyndia C. , Davis Stephanie D. , Kerby Gwendolyn S. , Kloster Margaret , Johnson Robin , Castile Robert , Hiatt Peter W. , Hart Meeghan , Rosenfeld Margaret
Published: June 2012

This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry.

Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability.

45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3–6.5 yrs. The median number of measurements per participant was 6 (range 3–9). RecentPseudomonas aeruginosainfection was associated with 5.1% (95% CI 0.01–9.9%) lower forced expiratory volume in 0.5 s (FEV0.5) and 16.4% (95% CI 7.0–24.9%) lower forced expiratory flow at 25–25% of forced vital capacity (FEF25–75%), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1–10.1%) lower FEV0.5and 10.1% (95% CI 0.6–18.7%) lower FEF25–75%. Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p<0.01 for each of FEV0.5, FEF25–75%and forced vital capacity).

RecentP. aeruginosainfection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.
Protecting the tuberculosis drug pipeline: stating the case for the rational use of fluoroquinolones
Authors: Migliori Giovanni Battista , Langendam Miranda W. , D'Ambrosio Lia , Centis Rosella , Blasi Francesco , Huitric Emma , Manissero Davide , van der Werf Marieke J.
Published: June 2012

The use of fluoroquinolones (FQs) to treat lower respiratory tract infections (LTRI) other than tuberculosis (TB) allows selection of FQ-resistant TB when TB is misdiagnosed. This study maps national guidelines on the use of FQs for LRTI in Europe and determines the risk of FQ-resistant TB upon FQ treatment before TB diagnosis.

A questionnaire was developed to map existing national LRTI and community-acquired pneumonia (CAP) guidelines. A systematic review and meta-analysis were performed to determine the risk of FQ-resistant TB if prescribed FQs prior to TB diagnosis.

15 (80%) out of 24 responding European Respiratory Society national delegates reported having national LRTI management guidelines, seven including recommendations on FQ use and one recommending FQs as the first-choice drug. 18 out of 24 countries had national CAP management guidelines, two recommending FQ as the drug of choice. Six studies investigating FQ exposure and the risk of FQ-resistant TB were analysed. TB patients had a three-fold higher risk of having FQ-resistant TB when prescribed FQs before TB diagnosis, compared to non FQ-exposed patients (OR 2.81, 95% CI 1.47–5.39).

Although the majority of European countries hold national LRTI/CAP guidelines, our results suggest that a risk of developing FQ resistance exists. Further strengthening of, and adherence to, guidelines is needed to ensure rational use of FQs.
Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension
Authors: Savale Laurent , Magnier Romain , Le Pavec Jérôme , Jaïs Xavier , Montani David , O'Callaghan Dermot S. , Humbert Marc , Dingemanse Jasper , Simonneau Gérald , Sitbon Olivier
Published: June 2012

Data on treatment of patients with portopulmonary hypertension (PoPH) are limited, as they are usually excluded from randomised controlled trials with pulmonary arterial hypertension (PAH)-specific therapies. This study investigated the short- and long-term efficacy/safety of bosentan in these patients, as well as its pharmacokinetics.

All 34 consecutive patients with PoPH treated with first-line bosentan (December 2002 to July 2009) were retrospectively evaluated. Assessments included the New York Heart Association functional class (NYHA FC), blood tests, haemodynamics, 6-min walk distance (6MWD) and event-free status. The pharmacokinetics of bosentan in five patients with Child–Pugh (C-P) class B cirrhosis were compared with idiopathic PAH patients.

Significant improvements from baseline were observed in NYHA FC, 6MWD and haemodynamics, and were largely maintained during follow-up. Patients with C-P class B cirrhosis (n=9) had significantly larger haemodynamic improvement after mean±sd5±2 months. Mean follow-up time was 43±19 months; four patients died and seven patients had significant elevation of liver enzymes (annual rate 5.5%). Plasma concentrations of bosentan were higher in patients with C-P class B cirrhosis than those observed in idiopathic PAH.

These data confirm the benefit of bosentan treatment for patients with PoPH. Haemodynamic improvements were particularly pronounced in patients with more severe cirrhosis. The safety profile of bosentan was consistent with previous studies.
PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis
Authors: Stephen Jancy , Delvecchio Chris , Spitale Naomi , Giesler Amanda , Radford Katherine , Bilan Pat , Cox P. Gerard , Capone John P. , Nair Parameswaran
Published: June 2012

Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome proliferator-activated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle (HASM) matrix production and migration.

PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPAR response element–luciferase reporter plasmid.

We observed that HASM cells express PPARα, β and γ. A six-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist, indicating endogenous PPAR activity. The PPAR ligands ciglitazone, 15-deoxy-Δ12,14-prostaglandin J2and WY-14643 decreased migration towards platelet-derived growth factor receptor. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through cyclooxygenase-2 induction and prostaglandin E2production that increased cyclic AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells.

We conclude that PPAR ligands decrease HASM migration and matrix production and are, therefore, potentially useful for modulating airway remodelling.
TLR9- and Src-dependent expression of Krueppel-like factor 4 controls interleukin-10 expression in pneumonia
Authors: Zahlten Janine , Steinicke Robert , Bertrams Wilhelm , Hocke Andreas C. , Scharf Stefanie , Schmeck Bernd , Witzenrath Martin , Hammerschmidt Sven , Suttorp Norbert , Hippenstiel Stefan
Published: June 2012

The release of potent pro-inflammatory mediators is crucial to mounting an efficient host response during infection. However, excessive inflammation may lead to deleterious tissue damage. This is highlighted in severe pneumococcal pneumonia, in which the delicate balance between a robust inflammatory response necessary to kill pneumococci and the loss of organ function determines the outcome of the disease.

We assessed the regulation of the potent anti-inflammatory cytokine interleukin (IL)-10 in pneumococcal infectionviaWestern blot, ELISA and chromatin immunoprecipitation analysis.

Streptococcus pneumoniaeinduced IL-10 expression in mouse lungs and human lung epithelial cells. Pneumococcal infection resulted in a strong induction of Krueppel-like factor (KLF)4 expressionin vivoandin vitro. The induction of both IL-10 and KLF4 is mediated by a pathway involving bacterial DNA, Toll-like receptor (TLR)9, MyD88 and Src kinase. KLF4 is recruited to theil10promoter, and small-interfering RNA-mediated knockdown of KLF4 expression blocked IL-10 expression during pneumococcal infection.

In conclusion, KLF4 is induced in a bacterial DNA–TLR9–Src-dependent manner and regulates IL-10 expression, linking the detection of bacterial DNA by TLR9 to the control of an inflammatory response.
Home mechanical ventilation in Australia and New Zealand
Authors: Garner Daniel J. , Berlowitz David J. , Douglas James , Harkness Nick , Howard Mark , McArdle Nigel , Naughton Matthew T. , Neill Alister , Piper Amanda , Yeo Aeneas , Young Alan
Published: June 2012

This study aims to describe the pattern of home mechanical ventilation (HMV) usage in Australia and New Zealand.

34 centres providing HMV in the region were identified and asked to complete a questionnaire regarding centre demographics, patient diagnoses, HMV equipment and settings, staffing levels and methods employed to implement and follow-up therapy.

28 (82%) centres responded, providing data on 2,725 patients. The minimum prevalence of HMV usage was 9.9 patients per 100,000 population in Australia and 12.0 patients per 100,000 population in New Zealand. Variation existed across Australian states (range 4–13 patients per 100,000 population) correlating with population density (r=0.82; p<0.05). The commonest indications for treatment were obesity hypoventilation syndrome (OHS) (31%) and neuromuscular disease (NMD) (30%). OHS was more likely to be treated in New Zealand, in smaller, newer centres, whilst NMD was more likely to be treated in Australia, in larger, older centres. Chronic obstructive pulmonary disease was an uncommon indication (8.0%). No consensus on indications for commencing treatment was found.

In conclusion, the prevalence of HMV usage varies across Australia and New Zealand according to centre location, size and experience. These findings can assist HMV service planning locally and highlight trends in usage that may be relevant in other countries.
A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations
Authors: Singh Dave , Kampschulte Jorg , Wedzicha Jadwiga A. , Jones Paul W. , Cohuet Géraldine , Corradi Massimo , Higenbottam Tim , Petruzzelli Stefano , Vestbo Jørgen
Published: June 2012

Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD).

The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology.

FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.
An earlier and more confident diagnosis of idiopathic pulmonary fibrosis
Authors: du Bois Roland M.
Published: June 2012

A diagnosis of idiopathic pulmonary fibrosis (IPF) has serious implications for the affected individuals, who have a 50% likelihood of dying within 2−3 yrs, an outcome which is worse than many cancers. A swift and accurate diagnosis is imperative, especially as commencing treatment at a relatively early disease stage may have the greatest impact on reducing disease progression.

The 2011, IPF guidelines provide updated and simplified IPF diagnostic criteria that may facilitate making a more confident diagnosis. The key investigational tool is high-resolution computed tomography (HRCT). In the presence of the four classical features, that together accurately identify a usual interstitial pneumonia (UIP) pattern, a definitive diagnosis of IPF can be made. When HRCT honeycombing is absent, even in the presence of all other features including traction bronchiectasis, the guidelines provide no designation for this constellation of features that many clinicians and radiologists would regard as consistent with UIP.

The diagnostic algorithm suggested by the 2011 guidelines emphasises the importance of multidisciplinary discussion between clinicians, radiologists and pathologists to improve diagnostic confidence. The course of disease in IPF is unpredictable, but the importance of an early diagnosis is clear, as individuals with less severe lung function abnormalities have a better prognosis.
Assessing the treatment effect from multiple trials in idiopathic pulmonary fibrosis
Authors: Richeldi Luca
Published: June 2012

The magnitude of treatment effect can be assessed by a number of methods. One method of collectively analysing data is that used by the Cochrane Collaboration. Their systematic reviews identify, analyse and present research-based evidence in an accessible format. These reviews may contain meta-analyses combining data from multiple studies to provide robust evaluations of overall treatment effects.

In 2003, Cochrane reviews of data for treatment with corticosteroids in idiopathic pulmonary fibrosis (IPF) found no evidence supporting their use; similarly, reviews of immunomodulatory agents found very little evidence to support their use.

A recent update of these Cochrane reviews failed to identify any evidence supporting the use of corticosteroids in IPF; however, a review of non-steroid agents in the treatment of IPF identified 15 clinical trials suitable for analysis. Two trials of interferon-γ-1b were combined, and no treatment effect was observed in terms of survival. Two Japanese trials of treatment with pirfenidone were combined, and a positive effect of pirfenidone on pulmonary function decline was observed. Meta-analysis of three phase III studies suggested that pirfenidone significantly increased progression-free survival by 30%.

The findings of this systematic review, although not presenting new original data, together with an acceptable safety profile, suggest that pirfenidone may have a role in IPF treatment.
The management of work-related asthma guidelines: a broader perspective
Authors: Baur Xaver , Aasen Tor Brøvig , Burge P. Sherwood , Heederik Dick , Henneberger Paul K. , Maestrelli Piero , Schlünssen Vivi , Vandenplas Olivier , Wilken Dennis
Published: June 2012

The aim of the European Respiratory Society work-related asthma guidelines is to present the management and prevention options of work-related asthma and their effectiveness.

Work-related asthma accounts for 5–25% of all adult asthma cases and is responsible for a significant socioeconomic burden. Several hundred occupational agents, mainly allergens but also irritants and substances with unknown pathological mechanisms, have been identified as causing work-related asthma.

The essential message of these guidelines is that the management of work-related asthma can be considerably optimised based on the present knowledge of causes, risk factors, pathomechanisms, and realistic and effective interventions. To reach this goal we urgently require greatly intensified primary preventive measures and improved case management. There is now a substantial body of evidence supporting the implementation of comprehensive medical surveillance programmes for workers at risk. Those workers who fail surveillance programmes need to be referred to a clinician who can confirm or exclude an occupational cause. Once work-related asthma is confirmed, a revised risk assessment in the workplace is needed to prevent further cases. These new guidelines confirm and extend already existing statements and recommendations.

We hope that these guidelines will initiate the much-needed research that is required to fill the gaps in our knowledge and to initiate substantial improvements in preventative measures.
Contribution of host factors and workplace exposure to the outcome of occupational asthma
Authors: Maestrelli Piero , Schlünssen Vivi , Mason Paola , Sigsgaard Torben
Published: June 2012

The outcome of occupational asthma after diagnosis is often poor. The identification of factors associated with a worse outcome may help in the management of the disease, determining its prognosis and assessing the permanent impairment attributable to occupational exposure.

The aim of this systematic review was to provide the available evidence from the medical literature to answer the question: “What is the contribution of host factors and workplace exposure to the risk of a bad outcome of occupational asthma?”

A systematic literature search was conducted in March 2010. We retrieved 177 abstracts. Of these, 67 were assessed as potentially relevant. After full text evaluation, 35 articles that were actually relevant for the question were included in the analysis.

The information obtained was sufficient to establish that older age, high-molecular-weight agents, impaired lung function and longer duration of exposure to the offending agent at the time of diagnosis had a negative role on the outcome of occupational asthma. Atopy and smoking at diagnosis did not seem to influence the outcome of occupational asthma. A limited number of studies considered sex and the pattern of asthmatic reaction on specific inhalation challenge and their findings were contradictory.