bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated diagnosis of epileptic electroencephalogram using independent component analysis and discrete wavelet transform for different electroencephalogram durations
Authors: UR Acharya , R Yanti , G Swapna , VS Sree , RJ Martis , JS Suri
Published: December 2012

Epilepsy is a disorder of the brain depicted by recurrent seizures. Electroencephalogram signals can be used to study the characteristics of epileptic seizures. In this study, we propose a method for the automated classification of electroencephalogram into normal, interictal and ictal classes using 6, 12, 18 and 23.6 s of data. We employed discrete wavelet transform to decompose electroencephalogram signals into frequency sub-bands. These discrete wavelet transform coefficients were then subjected to independent component analysis for reducing the data dimension. The independent component analysis features were then fed to six classifiers, namely, decision tree, K-nearest neighbor, probabilistic neural network, fuzzy, Gaussian mixture model and support vector machine to select the best classifier. We observed that the support vector machine classifier with radial basis function kernel function gave the best results with an average accuracy of 96%, sensitivity of 96% and specificity of 97% for 23.6 s of electroencephalogram data. Our results show that as the duration of the data increases, the classification accuracy increases. This proposed technique can be used as an automatic seizure monitoring software to aid the doctors in providing timely quality care for the patients suffering from epilepsy.
Haptically guided robotic technology in total hip arthroplasty: A cadaveric investigation
Authors: Nawabi Danyal H , Conditt Michael A , Ranawat Amar S , Dunbar Nicholas J , Jones Jennifer , Banks Scott , Padgett Douglas E
Published: December 2012

The longevity of total hip arthroplasty (THA) continues to improve with advancements in design and bearing materials. However, the incidence of dislocation and impingement-related failures continue to rise, with the inability of the surgeon to achieve optimal component orientation cited as a cause. Computer-assistance has been shown to increase the accuracy of component orientation and robotic-assistance has been developed to translate this advantage into precise surgical execution. We sought to validate a haptically-guided robotic arm system in performing THA with the aim of comparing the accuracy of robotic-assisted acetabular cup placement to manual placement. We implanted 12 acetabular components in 6 cadaveric pelvises comparing robotic-assistance on one side with manual implantation on the other. We measured planned and actual center of rotation (COR), cup position, leg-length equalization and offset for each THA using computed tomography and the robotic platform. The root-mean-square (RMS) error for the robotic-assisted system was within 3° for cup placement and within 1mm for leg-length equalization and offset when compared to computed tomography. The robotic-assisted system was significantly more accurate than manual implantation in reproducing the COR and cup orientation, as determined by a preoperative plan. The RMS error for manual implantation compared to robotic-assistance was 5 times higher for cup inclination and 3.4 times higher for cup anteversion ( p < 0.01). Robotic-assistance is more accurate than manual implantation in achieving optimal cup orientation. It has the ability to eliminate human error from THA and should be considered in light of THA failures due to component malposition.
Optical coherence tomography: A potential tool to predict premature rupture of fetal membranes
Authors: Micili Serap C , Valter Markus , Oflaz Hakan , Ozogul Candan , Linder Peter , Föckler Nicole , Artmann Gerhard M , Digel Ilya , Artmann Aysegul T
Published: December 2012

A fundamental question addressed in this study was the feasibility of preterm birth prediction based on a noncontact investigation of fetal membranes in situ. Although the phenomena of preterm birth and the premature rupture of the fetal membrane are well known, currently, there are no diagnostic tools for their prediction. The aim of this study was to assess whether optical coherence tomography could be used for clinical investigations of high-risk pregnancies. The thickness of fetal membranes was measured in parallel by optical coherence tomography and histological techniques for the following types of birth: normal births, preterm births without premature ruptures and births at full term with premature rupture of membrane. Our study revealed that the membrane thickness correlates with the birth type. Normal births membranes were statistically significantly thicker than those belonging to the other two groups. Thus, in spite of almost equal duration of gestation of the normal births and the births at full term with premature rupture, the corresponding membrane thicknesses differed. This difference is possibly related to previously reported water accumulation in the membranes. The optical coherence tomography results were encouraging, suggesting that this technology could be used in future to predict and distinguish between different kinds of births.
The Emotionally Intelligent Decision Maker
Authors: Yip Jeremy A. , Côté Stéphane
Published: December 2012

In two experiments, we examined how a core dimension of emotional intelligence, emotion-understanding ability, facilitates decision making. Individuals with higher levels of emotion-understanding ability can correctly identify which events caused their emotions and, in particular, whether their emotions stem from events that are unrelated to current decisions. We predicted that incidental feelings of anxiety, which are unrelated to current decisions, would reduce risk taking more strongly among individuals with lower rather than higher levels of emotion-understanding ability. The results of Experiment 1 confirmed this prediction. In Experiment 2, the effect of incidental anxiety on risk taking among participants with lower emotion-understanding ability, relative to participants with higher emotion-understanding ability, was eliminated when we informed participants about the source of their anxiety. This finding reveals that emotion-understanding ability guards against the biasing effects of incidental anxiety by helping individuals determine that such anxiety is irrelevant to current decisions.
Health Care Expenditures Among Asian American Subgroups
Authors: Chen Jie , Vargas-Bustamante Arturo , Ortega Alexander N.
Published: December 2012

Using two nationally representative data sets, this study examined health care expenditure disparities between Caucasians and different Asian American subgroups. Multivariate analyses demonstrate that Asian Americans, as a group, have significantly lower total expenditures compared with Caucasians. Results also point to considerable heterogeneities in health care spending within Asian American subgroups. Findings suggest that language assistance programs would be effective in reducing disparities among Caucasians and Asian American subgroups with the exception of Indians and Filipinos, who tend to be more proficient in English. Results also indicate that citizenship and nativity were major factors associated with expenditure disparities. Socioeconomic status, however, could not explain expenditure disparities. Results also show that Asian Americans have lower physician and pharmaceutical costs but not emergency department or hospital expenditures. These findings suggest the need for culturally competent policies specific to Asian American subgroups and the necessity to encourage cost-effective treatments among Asian Americans.
A case of combined bilothorax and bile peritonitis secondary to gunshot wounds in a cat
Authors: Murgia Daniela
Published: December 2012

This report describes a case of bile peritonitis and bilothorax associated with diaphragmatic laceration secondary to gunshot wounds in a cat. Surgical treatment comprising cholecystectomy, placement of a chest tube for thoracic lavage and tube feeding led to an uneventful recovery. Bilothorax and bile peritonitis are a rare presentation in cats. There are only four cases reported in the literature and combined bilothorax and bile peritonitis secondary to gunshot lesion has not been documented before. This report describes positioning of the chest tube for pleural lavage through the diaphragmatic defect created by a pellet’s trajectory. The tube was then allowed to exit the laparotomy incision instead of exiting the thoracic wall.
On the modeling and shape optimization of hydrodynamic flexible-pad thrust bearings
Authors: Fesanghary M , Khonsari MM
Published: December 2012

A theoretical analysis of a hydrodynamic thrust bearing with a flexible-pad design is presented. The flexibility of pads improves the load-carrying capacity (LCC) of the bearing for a wide range of loading conditions by providing an adaptive surface deformation mechanism. To accurately predict the behavior of flexible-pad thrust bearings, an appropriate multi-physics model that considers the coupled mechanism between the lubricant pressure and the pad deformation is developed. An optimization study is carried out that uses hybrid harmony search algorithm and sequential quadratic programming to find the optimum geometrical parameters of the pad for maximum LCC. In addition, an approximate analytical method for optimum bearing design is presented. The results of simulations reveal that the flexible-pad bearings provide up to 30% more LCC in comparison with conventional inclined pad thrust bearings.
Shifting responsibilities in Western European pension systems: What future for social models?
Authors: Ebbinghaus Bernhard , Whiteside Noel
Published: December 2012

A liberal paradigm shift from state to private responsibility in old age income protection has been a general development across Western Europe. The financial crisis sheds new light on the question of the public–private divide in pension policy. Applying convention theory, the analysis reviews how funded pensions are governed and how states use a range of regulation to control their operations as they seek to convert market-related practices to social policy purposes. The article argues that accruing state regulation consequent on coping with the financial crisis and its aftermath has undermined easy distinctions between public and private schemes, and is generating increasingly technocratic and oligarchic forms of pension governance, to the detriment of democratic debate on pensions.
The cross-border portability of supplementary pensions: Lessons from the European Union
Authors: Guardiancich Igor , Natali David
Published: December 2012

Over the past 40 years, the European Union (EU) has developed the most advanced system of coordination of social security rights in the world, as a corollary to the free movement of workers. Notwithstanding, problems with the acquisition, transfer and fruition of supplementary pension rights still undermine labour mobility across the member states. This article aims to describe EU pension regulation in the field and illustrates how the EU has employed two different approaches to tackle the problem. The first approach is to directly facilitate the portability of supplementary pension rights – which deeply affects national social policy. The second is to develop transnational schemes leading to a single market for occupational pensions – an exercise in market-making integration. This article explores the main problems in implementing the portability principle and puts forward tangible solutions to unblocking the situation. This sheds light on the persistent tensions between supranational regulation and national pension policy, showing the need for a holistic strategy to resolve both institutional and technical issues.
Isaiah Berlin’s thought and its legacy: Critical reflections on a symposium
Authors: Cherniss Joshua L.
Published: December 2012

The papers published in this issue of the EJPT discuss facets of the work of Isaiah Berlin from different perspectives and making use of varying intellectual approaches. At the same time, they focus attention on a few, central themes of Berlin's work: his complex relationship to liberalism and nationalism, his theories of liberty and value pluralism, and his perception and uses of the history of ideas. Consideration of the differences and overlap between these articles presents an occasion to take stock of Berlin's work as a whole; and a critical response to the interpretations and criticisms of Berlin presented here afford an opportunity to re-evaluate, criticize and defend central aspects of Berlin's intellectual position. This article goes beyond summary to present a critical, interpretive adjudication between the claims of Berlin's work, and the interpretations of that work presented in the other articles in this issue. Drawing on each of these, I present an interpretation of Berlin's contributions to thinking about the Enlightenment, nationalism and cultural pluralism, utopianism and political ethics, liberty, and value pluralism; I also consider the difficulties of interpreting Berlin's work, and applying his ideas today.
Berlin’s two concepts of positive liberty
Authors: Kis Janos
Published: December 2012

In ‘Two Concepts of Liberty’, Berlin wavered between two readings of the concept of positive liberty. In the first one, ‘positive liberty’ is a distinct concept, different from that of ‘negative liberty’. Those who advocate liberty in the negative sense and those who advocate it in the positive sense do not disagree on which interpretation of the same thing – ‘liberty’ – is the correct one; they speak about different things. Both defend valid ideals, although those ideals may not be simultaneously achievable. In the second reading, negative and positive liberty are competing interpretations of the same concept, the defenders of negative liberty being involved in a substantive disagreement with the advocates of positive liberty on what the same term – ‘liberty’ – really means. On this understanding, negative and positive liberty cannot both be valid ideals: one of them (negative liberty) is a genuine value, the other (positive liberty) being nothing but the perversion of it. My article aims to uncover the roots of this ambiguity in unresolved difficulties in Berlin’s account of the history of the ideas of negative and positive liberty and, more importantly, in his conception of value pluralism.
Retroperitoneal Laparoendoscopic Single-Site Radical Nephrectomy Using a Low-cost, Self-Made Device
Authors: Dong Jun , Zu Qiang , Shi Lixin , Gao Jiangping , Song Tao , Li Hongzhao , Sun Shengkun , Zhang Xu , Cai Wei
Published: December 2012

Objectives. To introduce a low-cost, self-made device for single-port retroperitoneal laparoscopic radical nephrectomy and to evaluate outcomes compared with conventional laparoscopy after initial experience using this device. Methods. Twenty-nine renal cancer patients underwent retroperitoneal laparoendoscopic single-site radical nephrectomy using a self-made single-port device with multiple manipulation channels for passage of routine laparoscopic instruments and specimen removal. A control group of 29 patients who were matched by age, gender, and cancer stage underwent conventional laparoscopy. Outcomes were analyzed retrospectively. Results. There were no significant differences in age, gender, body mass index, T stage, and maximum tumor diameter between groups ( P > .05). The laparoendoscopic single-site surgery group had a significantly shorter duration of postoperative hospitalization than the conventional laparoscopy group (7.14 ± 1.38 days vs 8.17 ± 1.54 days, P = .009). Conclusions. Retroperitoneal laparoscopic radical nephrectomy using our self-made single-port device appears to be a feasible, safe, and low-cost surgical strategy.
Evaluation of Recent Trends in Treatment Patterns Among Men With Benign Prostatic Hyperplasia
Authors: Kruep Eric J. , Goodwin Bridgett B. , Chaudhari Sham
Published: December 2012

Although there is an abundance of evidence regarding clinical efficacy and safety of benign prostatic hyperplasia (BPH) treatment, real-world evidence is lacking for pharmacotherapy utilization and trends. It is unclear how evidence demonstrating the efficacy of combination 5-alpha reductase inhibitors and alpha blockers for improving symptoms and reducing risk of disease progression translates into real-world practice for the treatment of BPH. A retrospective study of a database was conducted to describe pharmacotherapy utilization/trends in the treatment of BPH among patients in the managed care setting. After inclusion and exclusion criteria were applied, the final sample size was 107,038. The proportion of patients with BPH receiving 5-alpha reductase inhibitors therapy increased (21.1% in 2003 to 30.5% in 2007), as did the proportion receiving combination therapy (10.7% and 16.1%, respectively). We observed an almost 50% increase in 5-alpha reductase inhibitors use over 5 years and a 60% increase in the use of combination 5-alpha reductase inhibitors/alpha blockers therapy.
Escitalopram (Cipralex®) - Patent litigation in Europe
Authors: De Boer Henk
Published: December 2012

Lundbeck’s patents protecting their blockbuster Cipralex® have been subject to invalidation actions around the globe for already many years. Cipralex® is an antidepressant drug which contains as the active substance escitalopram, the (S)-enantiomer of the racemic mixture citalopram marketed amongst others as Cipramil®. Outside Europe, these actions have mainly been finalised. However, patent litigation is still continuing in Europe.
India: Similar biologics guidelines and implementation
Authors: Singhania Smita Suneel , Tripathi Krishan Kumar
Published: December 2012

Indian regulatory authorities for biologics, jointly at Department of Biotechnology and Central Drug Standard Control organization in association with the task force comprising Indian biologics manufacturers laid down the regulatory pathway for manufacturing and marketing authorization of similar biologics, claiming to be similar to an already authorized reference biologic. This guidance has come in force from 15 September 2012 in India. This guidance document is a simple abridged process for evaluation of ‘Similar Biologics’ that are approved and marketed either in India, Europe or USA or any other country for more than 4 years.
The vexed issue of therapeutic combinations and contributory patent infringement in Australia
Authors: Condon Wayne , Lambert Justin
Published: December 2012

The Australian Patents Act includes a provision which deems the supplier of a product to a person who will use that product in a manner which infringes a patent to infringe that patent as a contributory infringer. The concept of contributory patent infringement is one known to the patent laws of many countries, but in many respects the way in which Australian Courts have approached contributory patent infringement gives far greater scope to a patentee than in many of those jurisdictions. The consequence for the generic pharmaceutical industry in Australia is potentially far-reaching. This article looks at the practical consequences of some recent Australian Federal Court decisions which have been decided in the area and which create practical hurdles that any generic entrant into the Australian marketplace will need to navigate.
Mechanical and water barrier properties of soy protein isolate film incorporated with gelatin
Authors: Bai Huiyu , Xu Jing , Liao Ping , Liu Xiaoya
Published: December 2012

Soy protein isolate film modified with gelatin was prepared via solvent casting. The effect of gelatin contents on visual, mechanical, water barrier properties and surface hydrophobicity of the films was investigated. It showed that the film containing 30 wt% gelatin had higher tensile strength, elongation at break, contact angle, and lower water vapor transmission rate. Soy protein isolate/gelatin blend film structures were characterized by Fourier transform infrared. Compared with the other films, the 30 wt% gelatin composite film peak intensity is stronger at 1380 cm−1 and weaker at 1538 cm−1, indicating that the strong hydrogen bonding between –COOH in the soy protein isolate film and –NH2 in the gelatin led to exposing the –CH3 groups in the soy protein isolate film. Scanning electron microscopy showed that the 30 wt% gelatin composite film phase morphology was much finer than the other films. This confirmed that the 30 wt% gelatin soy protein isolate/gelatin composite film has good compatibility. The tests performed showed the potential for gelatin to improve the soy protein isolate film properties. This work provided a new approach to explore such films without plasticizer as biodegradable food packaging.
The polygenic nature of inhibitors in hemophilia A: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort
Authors: Astermark Jan , Donfield Sharyne M. , Gomperts Edward D. , Schwarz John , Menius Erika D. , Pavlova Anna , Oldenburg Johannes , Kessing Bailey , DiMichele Donna M. , Shapiro Amy D. , Winkler Cheryl A. , Berntorp Erik
Published: December 2012

Key Points

The data demonstrate the complexity of the genetic contribution to inhibitor development in people with hemophilia A. Potentially decisive markers have been identified, indicating the importance of further evaluation of intracellular signaling pathways.
Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells
Authors: Macari Elizabeth R. , Schaeffer Emily K. , West Rachel J. , Lowrey Christopher H.
Published: December 2012

Key Points

Simvastatin and tBHQ suppress KLF1 and BCL11 gene expression and additively increase fetal hemoglobin in primary human erythroid cells. Because both drugs are FDA-approved, these findings could lead to clinical trials in the relatively near future.
Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway
Authors: Li Yonghui , Gao Li , Luo Xufeng , Wang Lili , Gao Xiaoning , Wang Wei , Sun Junzhong , Dou Liping , Li Jingxin , Xu Chengwang , Wang Lixin , Zhou Minhang , Jiang Mengmeng , Zhou Jihao , Caligiuri Michael A. , Nervi Clara , Bloomfield Clara D. , Marcucci Guido , Yu Li
Published: December 2012

t(8;21) is one of the most frequent chromosomal translocations occurring in acute myeloid leukemia (AML) and is considered the leukemia-initiating event. The biologic and clinical significance of microRNA dysregulation associated with AML1/ETO expressed in t(8;21) AML is unknown. Here, we show that AML1/ETO triggers the heterochromatic silencing of microRNA-193a (miR-193a) by binding at AML1-binding sites and recruiting chromatin-remodeling enzymes. Suppression of miR-193a expands the oncogenic activity of the fusion protein AML-ETO, because miR-193a represses the expression of multiple target genes, such as AML1/ETO, DNMT3a, HDAC3, KIT, CCND1, and MDM2 directly, and increases PTEN indirectly. Enhanced miR-193a levels induce G1 arrest, apoptosis, and restore leukemic cell differentiation. Our study identifies miR-193a and PTEN as targets for AML1/ETO and provides evidence that links the epigenetic silencing of tumor suppressor genes miR-193a and PTEN to differentiation block of myeloid precursors. Our results indicated a feedback circuitry involving miR-193a and AML1/ETO/DNMTs/HDACs, cooperating with the PTEN/PI3K signaling pathway and contributing to leukemogenesis in vitro and in vivo, which can be successfully targeted by pharmacologic disruption of the AML1/ETO/DNMTs/HDACs complex or enhancement of miR-193a in t(8;21)–leukemias.
High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia
Authors: Pasquet Marlène , Bellanné-Chantelot Christine , Tavitian Suzanne , Prade Naïs , Beaupain Blandine , LaRochelle Olivier , Petit Arnaud , Rohrlich Pierre , Ferrand Christophe , Van Den Neste Eric , Poirel Hélène A. , Lamy Thierry , Ouachée-Chardin Marie , Mansat-De Mas Véronique , Corre Jill , Récher Christian , Plat Geneviève , Bachelerie Françoise , Donadieu Jean , Delabesse Eric
Published: December 2012

Key Points

Mutations of key transcription factor in myeloid malignancies.
An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe−/− mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia
Authors: Schmidt Paul J. , Toudjarska Iva , Sendamarai Anoop K. , Racie Tim , Milstein Stuart , Bettencourt Brian R. , Hettinger Julia , Bumcrot David , Fleming Mark D.
Published: December 2012

Key Points

Tmprss6 siRNA induces hepcidin and diminishes iron in hemochromatosis or thalassemia mice, improving the anemia seen in the latter model. Manipulation of TMPRSS6 with RNAi therapeutics may be an approach to treating iron overload diseases associated with low hepcidin levels.
Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP
Authors: Gérart Stéphane , Sibéril Sophie , Martin Emmanuel , Lenoir Christelle , Aguilar Claire , Picard Capucine , Lantz Olivier , Fischer Alain , Latour Sylvain
Published: December 2012

Invariant natural killer (iNKT) T cells and mucosal-associated invariant T (MAIT) cells represent peculiar T-lymphocyte subpopulations with innate-like properties that differ from conventional T cells. iNKT are reduced in the primary immunodeficiency caused by mutations in the X-linked inhibitor of apoptosis (XIAP). By studying the mechanism of this depletion, we herein report that iNKT cells exhibit a high susceptibility to apoptosis that is not observed with conventional T cells. Elevated expression of caspases 3 and 7 accounts for the proapoptotic phenotype of iNKT cells, which is inhibited by XIAP although it exerts a moderate effect in conventional T cells. Similarly, MAIT cells exhibit a proapoptotic propensity with elevated expression of activated caspases and are decreased in XIAP-deficient individuals. Knockdown of the transcription factor PLZF/ZBTB-16, which is involved in the effector program of iNKT cells, diminishes their proapoptotic phenotype. Conversely, overexpression of PLZF/ZBTB-16 in conventional T cells leads to a proapoptotic phenotype. Our findings identify a previously unknown pathway of regulation of innate-like T-cell homeostasis depending on XIAP and PLZF. The proapoptotic feature of iNKT cells also gives a reliable explanation of their exhaustion observed in different human conditions including the XIAP immunodeficiency.
Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics
Authors: Orsmark-Pietras Christina , James Anna , Konradsen Jon R. , Nordlund Björn , Söderhäll Cilla , Pulkkinen Ville , Pedroletti Christophe , Daham Kameran , Kupczyk Maciek , Dahlén Barbro , Kere Juha , Dahlén Sven-Erik , Hedlin Gunilla , Melén Erik
Published: December 2012

The causes of severe childhood asthma are poorly understood. Our aim was to define global patterns of gene expression in children with severe therapy-resistant and controlled asthma.

White blood cells were isolated and the global transcriptome profile was characterised using the Affymetrix Human Gene ST 1.0 chip in children with severe, therapy-resistant asthma (n=17), controlled asthma (n=19) and healthy controls (n=18). Receptor expression was studied in separated leukocyte fractions from asthmatic adults (n=12).

Overall, 1378 genes were differentially expressed between children with severe/controlled asthma and controls. Three significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were represented: natural killer cell-mediated cytotoxicity (upregulated in controlled asthma); N-glycan biosynthesis (downregulated in severe asthma); and bitter taste transduction receptors (TAS2Rs) (upregulated in severe asthma). Quantitative PCR experiments confirmed upregulation ofTAS2Rs in severe asthmatics.TAS2Rexpression was replicated in leukocytes from adult asthmatics, in whichTAS2Ragonists also inhibited LPS-induced cytokine release. Significant correlations between expression ofTAS2Rs and clinical markers of asthma severity were found in both adults and children.

In conclusion, specific gene expression patterns were observed in children with severe, therapy-resistant asthma. The increased expression of bronchodilatoryTAS2Rs suggests a new target for the treatment of asthma.
Scoring systems using chest radiographic features for the diagnosis of pulmonary tuberculosis in adults: a systematic review
Authors: Pinto Lancelot M. , Pai Madhukar , Dheda Keertan , Schwartzman Kevin , Menzies Dick , Steingart Karen R.
Published: December 2012

Chest radiography for the diagnosis of active pulmonary tuberculosis (PTB) is limited by poor specificity and reader inconsistency. Scoring systems have been employed successfully for improving the performance of chest radiography for various pulmonary diseases. We conducted a systematic review to assess the diagnostic accuracy and reproducibility of scoring systems for PTB.

We searched multiple databases for studies that evaluated the accuracy and reproducibility of chest radiograph scoring systems for PTB. We summarised results for specific radiographic features and scoring systems associated with PTB. Where appropriate, we estimated pooled performance of similar studies using a random effects model.

13 studies were included in the review, nine of which were in low tuberculosis (TB) burden settings. No scoring system was based solely on radiographic findings. All studies used systems with various combinations of clinical and radiological features. 11 studies involved scoring systems that were used for making decisions concerning hospital respiratory isolation. None of the included studies reported data on intra- or inter-reporter reproducibility. Upper lobe infiltrates (pooled diagnostic OR 3.57, 95% CI 2.38–5.37, five studies) and cavities (diagnostic OR range 1.97–25.66, three studies) were significantly associated with PTB. Sensitivities of the scoring systems were high (median 96%, IQR 93–98%), but specificities were low (median 46%, IQR 35–50%).

Chest radiograph scoring systems appear useful in ruling out PTB in hospitals, but their low specificity precludes ruling in PTB. There is a need to develop accurate scoring systems for people living with HIV and for outpatient settings, especially in high TB burden settings.
Obesity is associated with improved survival in community-acquired pneumonia
Authors: Singanayagam Anika , Singanayagam Aran , Chalmers James D.
Published: December 2012

Obesity has been identified as a risk factor for adverse outcomes of 2009 H1N1 influenza. However, the impact of obesity on outcomes of infection remains controversial. There are limited data investigating the effect of obesity on outcomes of community-acquired pneumonia (CAP).

This prospective observational study included patients presenting with CAP who had body mass index (BMI) measured on admission. Outcome measures included 30-day mortality and need for mechanical ventilation or inotropic support (MV/IS).

1079 patients were included, with 21% classified as obese (BMI ≥30 kg·m−2). Obesity was independently associated with reduced 30-day mortality from CAP on multivariate analysis (HR 0.53, 95% CI 0.29–0.98). This was not explained by differences in severity of disease on admission or requirement for MV/IS between obese and nonobese groups. Obese patients had higher median C-reactive protein levels and a higher frequency of sepsis using the systemic inflammatory response syndrome criteria (72.4%versus64.1%; p=0.03), than nonobese patients, suggesting greater systemic inflammation.

Obesity was associated with reduced 30-day mortality in patients hospitalised with CAP.
Multicomponent indices to predict survival in COPD: the COCOMICS study
Authors: Marin Jose M. , Alfageme Inmaculada , Almagro Pere , Casanova Ciro , Esteban Cristobal , Soler-Cataluña Juan J. , de Torres Juan P. , Martínez-Camblor Pablo , Miravitlles Marc , Celli Bartolome R. , Soriano Joan B.
Published: December 2012

Guidelines recommend defining chronic obstructive pulmonary disease (COPD) by airflow obstruction and other factors, but no studies have evaluated the ability of existing multicomponent indices to predict mortality up to 10 years.

We conducted a patient-based pooled analysis. Survival analysis and C statistics were used to determine the best COPD index/indices according to several construct variables and by varying time-points. Individual data of 3633 patients from 11 COPD cohorts were collected, totalling the experience of 15 878 person-years.

Overall, there were 1245 death events within our cohorts, with a Kaplan–Meier survival of 0.963 at 6 months, which was reduced to 0.432 at 10 years. In all patients, ADO (age, dyspnoea and forced expiratory volume in 1 s), BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) and e-BODE (BODE plus exacerbations) were the best indices to predict 6-month mortality. The ADO index was the best to predict 12-month (C statistic 0.702), 5-year (C statistic 0.695) and 10-year mortality (C statistic 0.698), and was significantly better than BODE (all p<0.05). The best indices to predict death by C statistics when adjusting by age were e-BODE, BODEx (substitution of exacerbations for exercise capacity) and BODE.

No index predicts short-term survival of COPD well. All BODE modifications scored better than ADO after age adjustment. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients.
Prevalence and prognosis of unclassifiable interstitial lung disease
Authors: Ryerson Christopher J. , Urbania Thomas H. , Richeldi Luca , Mooney Joshua J. , Lee Joyce S. , Jones Kirk D. , Elicker Brett M. , Koth Laura L. , King Talmadge E. , Wolters Paul J. , Collard Harold R.
Published: December 2012

The aim of this study was to determine the prevalence, characteristics and outcomes of patients with unclassifiable interstitial lung disease (ILD) and to develop a simple method of predicting disease behaviour.

Unclassifiable ILD patients were identified from an ongoing longitudinal cohort. Unclassifiable ILD was diagnosed after a multidisciplinary review did not secure a specific ILD diagnosis. Clinical characteristics and outcomes were compared with idiopathic pulmonary fibrosis (IPF) and non-IPF ILDs. Independent predictors of mortality were determined using Cox proportional-hazards analysis to identify subgroups with distinct disease behaviour.

Unclassifiable ILD was diagnosed in 10% of the ILD cohort (132 out of 1370 patients). The most common reason for being unclassifiable was missing histopathological assessment due to a high risk of surgical lung biopsy. Demographic and physiological features of unclassifiable ILD were intermediate between IPF and non-IPF disease controls. Unclassifiable ILD had longer survival rates when compared to IPF on adjusted analysis (hazard ratio 0.62, p = 0.04) and similar survival compared to non-IPF ILDs (hazard ratio 1.54, p = 0.12). Independent predictors of survival in unclassifiable ILD included diffusion capacity of the lung for carbon monoxide (p = 0.001) and a radiological fibrosis score (p = 0.02).

Unclassifiable ILD represents approximately 10% of ILD cases and has a heterogeneous clinical course, which can be predicted using clinical and radiological variables.
Pulsus paradoxus
Authors: Hamzaoui Olfa , Monnet Xavier , Teboul Jean-Louis
Published: December 2012

Systolic blood pressure normally falls during quiet inspiration in normal individuals. Pulsus paradoxus is defined as a fall of systolic blood pressure of >10 mmHg during the inspiratory phase. Pulsus paradoxus can be observed in cardiac tamponade and in conditions where intrathoracic pressure swings are exaggerated or the right ventricle is distended, such as severe acute asthma or exacerbations of chronic obstructive pulmonary disease. Both the inspiratory decrease in left ventricular stroke volume and the passive transmission to the arterial tree of the inspiratory decrease in intrathoracic pressure contribute to the occurrence of pulsus paradoxus. During cardiac tamponade and acute asthma, biventricular interdependence (series and parallel) plays an important role in the inspiratory decrease in left ventricular stroke volume.

Early recognition of pulsus paradoxus in the emergency room can help to diagnose rapidly cardiac tamponade. Measurement of pulsus paradoxus is also useful to assess the severity of acute asthma as well as its response to therapy. Recent development of noninvasive devices capable of automatic calculation and display of arterial pressure variation or derived indices should help improve the assessment of pulsus paradoxus at the bedside.
Reliability and validity of 4-metre gait speed in COPD
Authors: Kon Samantha S.C. , Patel Mehul S. , Canavan Jane L. , Clark Amy L. , Jones Sarah E. , Nolan Claire M. , Cullinan Paul , Polkey Michael I. , Man William D-C.
Published: December 2012

In community-dwelling older adults, usual gait speed over 4 m (4MGS) consistently predicts greater risk of adverse health outcomes. The aims of the present study were to assess the reliability of the 4MGS and the relationship with established health outcome measures in chronic obstructive pulmonary disease (COPD).

Test-retest and interobserver reliability of the 4MGS were measured in 80 and 58 COPD patients, respectively. In 586 COPD patients, the 4MGS, as well as forced expiratory volume in 1 s (FEV1), the incremental shuttle walk (ISW), Medical Research Council (MRC) dyspnoea scale and St George’s Respiratory Questionnaire (SGRQ) were measured. Participants were stratified according to “slow” (<0.8 m·s−1) or “normal” 4MGS (≥0.8 m·s−1).

Intra-class correlation coefficients for test-retest and interobserver reliability were 0.97 and 0.99, respectively. There was a significant positive correlation between 4MGS with ISW (ρ = 0.78; p<0.001) and a negative correlation with MRC dyspnoea scale and SGRQ (ρ = -0.55 and -0.44; p<0.001 for both). COPD patients with slow 4MGS had significantly reduced ISW and higher MRC dyspnoea scale and SGRQ than those with preserved walking speed, despite similar FEV1% predicted.

The 4MGS is reliable in COPD, correlates with exercise capacity, dyspnoea and health-related quality of life, and has potential as a simple assessment tool in COPD.
Multidrug-resistant tuberculosis in children: evidence from global surveillance
Authors: Zignol Matteo , Sismanidis Charalambos , Falzon Dennis , Glaziou Philippe , Dara Masoud , Floyd Katherine
Published: December 2012

Multidrug-resistant tuberculosis (MDR-TB) can affect persons of any age, but it remains unknown whether children are more or less likely than adults to have MDR-TB.

Representative drug resistance surveillance data reported to the World Health Organization between 1994 and 2011 were analysed to test the association between MDR-TB and age group (children aged <15 yearsversusadults aged ≥15 years), using odds ratios derived by logistic regression with robust standard errors.

Of 85 countries with data from nationwide surveys or surveillance systems, 35 reported at least one paediatric MDR-TB case. Aggregated data on age and drug susceptibility testing for 323 046 tuberculosis cases notified in these 35 countries were analysed. Odds ratios for MDR-TB in children compared to adults varied widely between countries. In Germany, Namibia, South Africa, the UK and the USA, MDR-TB was positively associated with age <15 years. In the remaining countries no association was established.

Despite the limitations intrinsic to the use of surveillance data and to the challenges of diagnosing childhood tuberculosis, our analysis suggests that proportions of MDR-TB in children and adults are similar in many settings. Of particular concern is the association found between age <15 years and MDR-TB in southern African countries with high HIV prevalence.
Selected clinical highlights from the 2012 ERS congress in Vienna
Authors: Marvisi Maurizio , Herth Felix J.F. , Ley Sebastian , Poletti Venerino , Chavannes Niels H. , Spruit Martijn A. , Clini Enrico , Cottin Vincent
Published: December 2012

This article reviews a selection of scientific presentations at the 2012 European Respiratory Society Annual Congress in Vienna, Austria. The best abstracts from the groups of the Clinical Assembly (Clinical Problems, Rehabilitation and Chronic Care, Imaging, Interventional Pulmonology, Diffuse Parenchymal Lung Disease, and General Practice and Primary Care) are presented and discussed in the context of the most up-to-date literature. The reviewed topics especially deal with the areas of chronic obstructive pulmonary disease (acute exacerbations, comorbidities, prognosis and rehabilitation), the diagnosis and management of idiopathic pulmonary fibrosis, sarcoidosis, endobronchial techniques in emphysema, functional imaging and issues in respiratory medicine relevant for the primary care setting, including aspects related to end-of-life care and palliation.
Accuracy of direct genomic breeding values for nationally evaluated traits in US Limousin and Simmental beef cattle
Authors: Saatchi Mahdi , Schnabel Robert D , Rolf Megan M , Taylor Jeremy F , Garrick Dorian J
Published: December 2012

Background

In national evaluations, direct genomic breeding values can be considered as correlated traits to those for which phenotypes are available for traditional estimation of breeding values. For this purpose, estimates of the accuracy of direct genomic breeding values expressed as genetic correlations between traits and their respective direct genomic breeding values are required.

Methods

We derived direct genomic breeding values for 2239 registered Limousin and 2703 registered Simmental beef cattle genotyped with either the Illumina BovineSNP50 BeadChip or the Illumina BovineHD BeadChip. For the 264 Simmental animals that were genotyped with the BovineHD BeadChip, genotypes for markers present on the BovineSNP50 BeadChip were extracted. Deregressed estimated breeding values were used as observations in weighted analyses that estimated marker effects to derive direct genomic breeding values for each breed. For each breed, genotyped individuals were clustered into five groups using K-means clustering, with the aim of increasing within-group and decreasing between-group pedigree relationships. Cross-validation was performed five times for each breed, using four groups for training and the fifth group for validation. For each trait, we then applied a weighted bivariate analysis of the direct genomic breeding values of genotyped animals from all five validation sets and their corresponding deregressed estimated breeding values to estimate variance and covariance components.

Results

After minimizing relationships between training and validation groups, estimated genetic correlations between each trait and its direct genomic breeding values ranged from 0.39 to 0.76 in Limousin and from 0.29 to 0.65 in Simmental. The efficiency of selection based on direct genomic breeding values relative to selection based on parent average information ranged from 0.68 to 1.28 in genotyped Limousin and from 0.51 to 1.44 in genotyped Simmental animals. The efficiencies were higher for 323 non-genotyped young Simmental animals, born after January 2012, and ranged from 0.60 to 2.04.

Conclusions

Direct genomic breeding values show promise for routine use by Limousin and Simmental breeders to improve the accuracy of predicted genetic merit of their animals at a young age and increase response to selection. Benefits from selecting on direct genomic breeding values are greater for breeders who use natural mating sires in their herds than for those who use artificial insemination sires. Producers with unregistered commercial Limousin and Simmental cattle could also benefit from being able to identify genetically superior animals in their herds, an opportunity that has in the past been limited to seed stock animals.
R-spondins are involved in the ovarian differentiation in a teleost, medaka (Oryzias latipes)
Authors: Zhou Linyan , Charkraborty Tapas , Yu Xiangguo , Wu Limin , Liu Gang , Mohapatra Sipra , Wang Deshou , Nagahama Yoshitaka
Published: December 2012

Background

In mammals, R-spondin (Rspo), an activator of the Wnt/β-catenin signaling pathway, has been shown to be involved in ovarian differentiation. However, the role of the Rspo/Wnt/β-catenin signaling pathway in fish gonads is still unknown.

Results

In the present study, full-length cDNAs of Rspo1, 2 and 3 were cloned from the gonads of medaka (Oryzias latipes). The deduced amino acid sequences of mRspo1-3 were shown to have a similar structural organization. Phylogenetic analysis showed that Rspo1, 2 and 3 were specifically clustered into three distinct clads. Tissue distribution revealed that three Rspo genes were abundantly expressed in the brain and ovary. Real-time PCR analysis around hatching (S33-5dah) demonstrated that three Rspo genes were specifically enhanced in female gonads from S38. In situ hybridization (ISH) analysis demonstrated that three Rspo genes were expressed in the germ cell in ovary, but not in testis. Fluorescence multi-color ISH showed that Rspo1 was expressed in both somatic cells and germ cells at 10dah. Exposure to ethinylestradiol (EE2) in XY individuals for one week dramatically enhanced the expression of three Rspo genes both at 0dah and in adulthood.

Conclusions

These results suggest that the Rspo-activating signaling pathway is involved in the ovarian differentiation and maintenance in medaka.
Stage-specific expression of protease genes in the apicomplexan parasite, Eimeria tenella
Authors: Katrib Marilyn , Ikin Rowan J , Brossier Fabien , Robinson Michelle , Slapetova Iveta , Sharman Philippa A , Walker Robert A , Belli Sabina I , Tomley Fiona M , Smith Nicholas C
Published: December 2012

Background

Proteases regulate pathogenesis in apicomplexan parasites but investigations of proteases have been largely confined to the asexual stages of Plasmodium falciparum and Toxoplasma gondii. Thus, little is known about proteases in other Apicomplexa, particularly in the sexual stages. We screened the Eimeria tenella genome database for proteases, classified these into families and determined their stage specific expression.

Results

Over forty protease genes were identified in the E. tenella genome. These were distributed across aspartic (three genes), cysteine (sixteen), metallo (fourteen) and serine (twelve) proteases. Expression of at least fifteen protease genes was upregulated in merozoites including homologs of genes known to be important in host cell invasion, remodelling and egress in P. falciparum and/or T. gondii. Thirteen protease genes were specifically expressed or upregulated in gametocytes; five of these were in two families of serine proteases (S1 and S8) that are over-represented in the coccidian parasites, E. tenella and T. gondii, distinctive within the Apicomplexa because of their hard-walled oocysts. Serine protease inhibitors prevented processing of EtGAM56, a protein from E. tenella gametocytes that gives rise to tyrosine-rich peptides that are incorporated into the oocyst wall.

Conclusion

Eimeria tenella possesses a large number of protease genes. Expression of many of these genes is upregulated in asexual stages. However, expression of almost one-third of protease genes is upregulated in, or confined to gametocytes; some of these appear to be unique to the Coccidia and may play key roles in the formation of the oocyst wall, a defining feature of this group of parasites.