bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic and Renal-Specific Sympathoinhibition in Obesity Hypertension
Authors: Lohmeier Thomas E. , Iliescu Radu , Liu Boshen , Henegar Jeffrey R. , Maric-Bilkan Christine , Irwin Eric D.
Published: December 2011

Chronic pressure-mediated baroreflex activation suppresses renal sympathetic nerve activity. Recent observations indicate that chronic electric activation of the carotid baroreflex produces sustained reductions in global sympathetic activity and arterial pressure. Thus, we investigated the effects of global and renal specific suppression of sympathetic activity in dogs with sympathetically mediated, obesity-induced hypertension by comparing the cardiovascular, renal, and neurohormonal responses to chronic baroreflex activation and bilateral surgical renal denervation. After control measurements, the diet was supplemented with beef fat, whereas sodium intake was held constant. After 4 weeks on the high-fat diet, when body weight had increased ≈50%, fat intake was reduced to a level that maintained this body weight. This weight increase was associated with an increase in mean arterial pressure from 100±2 to 117±3 mm Hg and heart rate from 86±3 to 130±4 bpm. The hypertension was associated with a marked increase in cumulative sodium balance despite an approximately 35% increase in glomerular filtration rate. The importance of increased tubular reabsorption to sodium retention was further reflected by ≈35% decrease in fractional sodium excretion. Subsequently, both chronic baroreflex activation (7 days) and renal denervation decreased plasma renin activity and abolished the hypertension. However, baroreflex activation also suppressed systemic sympathetic activity and tachycardia and reduced glomerular hyperfiltration while increasing fractional sodium excretion. In contrast, glomerular filtration rate increased further after renal denervation. Thus, by improving autonomic control of cardiac function and diminishing glomerular hyperfiltration, suppression of global sympathetic activity by baroreflex activation may have beneficial effects in obesity beyond simply attenuating hypertension.
Lack of Validation of a Same-Day Outpatient Protocol for Determination of Salt Sensitivity of Blood Pressure
Authors: Nichols JoAnn , Elijovich Fernando , Laffer Cheryl L.
Published: December 2011

Salt sensitivity of blood pressure has been studied in humans with a 48-hour inpatient protocol of salt loading and depletion or with longer outpatient protocols using high- and low-salt diets. Results have been reproducible, but both methods are laborious and costly. A 6-hour protocol of intravenous salt loading and furosemide has been reported but never validated. We studied 14 normal volunteers (39±2 years old; 86% women and 21% black) with the inpatient and 6-hour protocols, separated by 30 days. Four subjects (29%) were salt sensitive in the inpatient protocol. They had higher systolic blood pressure, higher body mass index, and somewhat lower plasma renin activity than salt-resistant subjects. Baseline systolic blood pressure before both protocols was highly reproducible (
r
=0.90;
P
<0.0001; limits of agreement: +6.2 to −8.0 mm Hg), whereas the response to salt depletion was not (
r
=0.09). Three salt-sensitive and 4 salt-resistant subjects were misclassified by the short protocol. Three-hour natriuresis by furosemide in the short protocol (344±15 mmol) was not different from the 12-hour natriuresis in the inpatient protocol (357±19). However, stimulation of plasma renin activity and aldosterone was significantly less in the short (+0.10±0.07 ngA
I
/L/sec and −61±44 pmol/L) than in the inpatient protocol (+1.80±0.60 ngA
I
/L/sec and +256±88 pmol/L;
P
<0.03 for both). Activation of hormonal changes that regulate depressor responses to salt depletion may not have occurred with the 3-hour natriuresis of the short protocol. This methodology cannot be used to study salt sensitivity of blood pressure, because the phenotype, mechanisms, and prognosis of the latter have been defined with the inpatient protocol.
Processing of Facial Emotion in the Human Fusiform Gyrus
Authors: Kawasaki Hiroto , Tsuchiya Naotsugu , Kovach Christopher K. , Nourski Kirill V. , Oya Hiroyuki , Howard Matthew A. , Adolphs Ralph
Published: December 2011

Electrophysiological and fMRI-based investigations of the ventral temporal cortex of primates provide strong support for regional specialization for the processing of faces. These responses are most frequently found in or near the fusiform gyrus, but there is substantial variability in their anatomical location and response properties. An outstanding question is the extent to which ventral temporal cortex participates in processing dynamic, expressive aspects of faces, a function usually attributed to regions near the superior temporal cortex. Here, we investigated these issues through intracranial recordings from eight human surgical patients. We compared several different aspects of face processing (static and dynamic faces; happy, neutral, and fearful expressions) with power in the high-gamma band (70–150 Hz) from a spectral analysis. Detailed mapping of the response characteristics as a function of anatomical location was conducted in relation to the gyral and sulcal pattern on each patient's brain. The results document responses with high responsiveness for static or dynamic faces, often showing abrupt changes in response properties between spatially close recording sites and idiosyncratic across different subjects. Notably, strong responses to dynamic facial expressions can be found in the fusiform gyrus, just as can responses to static faces. The findings suggest a more complex, fragmented architecture of ventral temporal cortex around the fusiform gyrus, one that includes focal regions of cortex that appear relatively specialized for either static or dynamic aspects of faces.
The Time Course of Visual Letter Perception
Authors: Madec Sylvain , Rey Arnaud , Dufau Stéphane , Klein Michael , Grainger Jonathan
Published: December 2011

We describe a novel method for tracking the time course of visual identification processes, here applied to the specific case of letter perception. We combine a new behavioral measure of letter identification times with single-letter ERP recordings. Letter identification processes are considered to take place in those time windows in which the behavioral measure and ERPs are correlated. A first significant correlation was found at occipital electrode sites around 100 msec poststimulus onset that most likely reflects the contribution of low-level feature processing to letter identification. It was followed by a significant correlation at fronto-central sites around 170 msec, which we take to reflect letter-specific identification processes, including retrieval of a phonological code corresponding to the letter name. Finally, significant correlations were obtained around 220 msec at occipital electrode sites that may well be due to the kind of recurrent processing that has been revealed recently by TMS studies. Overall, these results suggest that visual identification processes are likely to be composed of a first (and probably preconscious) burst of visual information processing followed by a second reentrant processing on visual areas that could be critical for the conscious identification of the visual target.
Extinguishing Extinction: Hemispheric Differences in the Modulation of TMS-induced Visual Extinction by Directing Covert Spatial Attention
Authors: Bien Nina , Goebel Rainer , Sack Alexander T.
Published: December 2011

The topic of spatial attention is of great relevance for researchers in various fields, including neuropsychology, cognitive neuroscience, and cognitive psychology, as well as for clinical practice. Deficits of spatial attentional arising from parietal brain damage remain largely confined to the left visual field. The mechanisms underlying this hemispheric asymmetry are still elusive. We mimicked the neuropsychological syndrome of contralesional extinction by temporarily inducing a spatial attentional bias in healthy volunteers with TMS. We investigated whether directing covert spatial attention could enhance or, more importantly, counteract the resulting behavioral deficits. Although both the left and right parietal TMS induced contralateral extinction, only left hemifield extinction following right parietal TMS was severely aggravated by a competing stimulus in the ipsilesional (right) hemifield. We put forward the hypothesis that an asymmetry with respect to the ability of detaching attention from a distractor is contributing to the right hemispheric lateralization with regard to extinction. On a broader level, we suggest that “virtual patients” might be used for evaluating neuropsychological treatment in an early stage of development, reducing the burden on actual patients.
Differential Sensitivity of Letters, Numbers, and Symbols to Character Transpositions
Authors: Duñabeitia Jon Andoni , Dimitropoulou Maria , Grainger Jonathan , Hernández Juan Andrés , Carreiras Manuel
Published: December 2011

This study was designed to explore whether the human visual system has different degrees of tolerance to character position changes for letter strings, digit strings, and symbol strings. An explicit perceptual matching task was used (same–different judgment), and participants' electrophysiological activity was recorded. Materials included trials in which the referent stimulus and the target stimulus were identical or differed either by two character replacements or by transposing two characters. Behavioral results showed clear differences in the magnitude of the transposed-character effect for letters as compared with digit and symbol strings. Electrophysiological data confirmed this observation, showing an N2 character transposition effect that was only present for letter strings. An earlier N1 transposition effect was also found for letters but was absent for symbols and digits, whereas a later P3 effect was found for all types of string. These results provide evidence for a position coding mechanism that is specific to letter strings, that was most prominent in an epoch between 200 and 325 msec, and that operates in addition to more general-purpose position coding mechanisms.
Climate System Response to External Forcings and Climate Change Projections in CCSM4
Authors: Meehl Gerald A. , Washington Warren M. , Arblaster Julie M. , Hu Aixue , Teng Haiyan , Tebaldi Claudia , Sanderson Benjamin N. , Lamarque Jean-Francois , Conley Andrew , Strand Warren G. , White James B.
Published: December 2011

Results are presented from experiments performed with the Community Climate System Model, version 4 (CCSM4) for the Coupled Model Intercomparison Project phase 5 (CMIP5). These include multiple ensemble members of twentieth-century climate with anthropogenic and natural forcings as well as single-forcing runs, sensitivity experiments with sulfate aerosol forcing, twenty-first-century representative concentration pathway (RCP) mitigation scenarios, and extensions for those scenarios beyond 2100–2300. Equilibrium climate sensitivity of CCSM4 is 3.20°C, and the transient climate response is 1.73°C. Global surface temperatures averaged for the last 20 years of the twenty-first century compared to the 1986–2005 reference period for six-member ensembles from CCSM4 are +0.85°, +1.64°, +2.09°, and +3.53°C for RCP2.6, RCP4.5, RCP6.0, and RCP8.5, respectively. The ocean meridional overturning circulation (MOC) in the Atlantic, which weakens during the twentieth century in the model, nearly recovers to early twentieth-century values in RCP2.6, partially recovers in RCP4.5 and RCP6, and does not recover by 2100 in RCP8.5. Heat wave intensity is projected to increase almost everywhere in CCSM4 in a future warmer climate, with the magnitude of the increase proportional to the forcing. Precipitation intensity is also projected to increase, with dry days increasing in most subtropical areas. For future climate, there is almost no summer sea ice left in the Arctic in the high RCP8.5 scenario by 2100, but in the low RCP2.6 scenario there is substantial sea ice remaining in summer at the end of the century.
Impact of Assimilating Microwave Radiances with a Limited-Area Ensemble Data Assimilation System on Forecasts of Typhoon Morakot
Authors: Schwartz Craig S. , Liu Zhiquan , Chen Yongsheng , Huang Xiang-Yu
Published: December 2011

Two parallel experiments were designed to evaluate whether assimilating microwave radiances with a cyclic, limited-area ensemble adjustment Kalman filter (EAKF) could improve track, intensity, and precipitation forecasts of Typhoon Morakot (2009). The experiments were configured identically, except that one assimilated microwave radiances and the other did not. Both experiments produced EAKF analyses every 6 h between 1800 UTC 3 August and 1200 UTC 9 August 2009, and the mean analyses initialized 72-h Weather Research and Forecasting model forecasts. Examination of individual forecasts and average error statistics revealed that assimilating microwave radiances ultimately resulted in better intensity forecasts compared to when radiances were withheld. However, radiance assimilation did not substantially impact track forecasts, and the impact on precipitation forecasts was mixed. Overall, net positive results suggest that assimilating microwave radiances with a limited-area EAKF system is beneficial for tropical cyclone prediction, but additional studies are needed.
Conceptualization and Measurement of Team Workload
Authors: Funke Gregory J. , Knott Benjamin A. , Salas Eduardo , Pavlas Davin , Strang Adam J.
Published: December 2011

Objective: The purpose of this article is to present and expand on current theories and measurement techniques for assessing team workload.

Background: To date, little research has been conducted on the workload experienced by teams. A validated theory describing team workload, which includes an account of its relation to individual workload, has not been articulated.

Method: The authors review several theoretical approaches to team workload. Within the team research literature, attempts to evaluate team workload have typically relied on measures of individual workload. This assumes that such measures retain their validity at the team level of measurement, but empirical research suggests that this method may lack sensitivity to the drivers of team workload.

Results: On the basis of these reviews, the authors advance suggestions concerning a comprehensive theory of team workload and methods for assessing it in team settings. The approaches reviewed include subjective, performance, physiological, and strategy shift measures. Theoretical and statistical difficulties associated with aggregating individual-level workload responses to a team-level measure are discussed.

Conclusion: Conception and measurement of team workload have not significantly matured alongside developments in individual workload.

Application: Team workload remains a complex research area without simple measurement solutions, but as a research domain it remains open for contributions from interested and enterprising researchers.
GPU-based parallel collision detection for fast motion planning
Authors: Pan Jia , Manocha Dinesh
Published: December 2011

We present parallel algorithms to accelerate collision queries for sample-based motion planning. Our approach is designed for current many-core GPUs and exploits data-parallelism and multi-threaded capabilities. In order to take advantage of the high number of cores, we present a clustering scheme and collision-packet traversal to perform efficient collision queries on multiple configurations simultaneously. Furthermore, we present a hierarchical traversal scheme that performs workload balancing for high parallel efficiency. We have implemented our algorithms on commodity NVIDIA GPUs using CUDA and can perform 500, 000 collision queries per second with our benchmarks, which is 10 times faster than prior GPU-based techniques. Moreover, we can compute collision-free paths for rigid and articulated models in less than 100 ms for many benchmarks, almost 50–100 times faster than current CPU-based PRM planners.
In/Between Feminism and Foucault: Iraqi Women’s War Blogs and Intellectual Practices of the Self
Authors: Campbell Perri , Kelly Peter
Published: December 2011

In this article we inquire into the forms of intellectual work that are possible when non-Muslim, non-Arab, western academics (female PhD candidate, male PhD supervisor) seek to work together to analyse the war-blogs of a small number of Iraqi women. We confront the central challenge of how to understand and account for such things as freedom, choice, self, gender, politics and relationships in the stories these women tell about themselves. We discuss how, in working in/between Foucault and feminism, it is possible to establish spaces in which a useful, though provisional and shifting, vocabulary of critique can emerge. Our aim is not to be for or against feminism or Foucault. Our position is that Foucault’s vocabulary of enlightenment and critique provides a means to think and talk about how we approach the task of accounting for the selves that we encounter in Iraqi women’s blogs.
Where the grass is greener: social segregation in three major Polish cities at the beginning of the 21st century
Authors: Marcińczak Szymon , Musterd Sako , Stępniak Marcin
Published: December 2011

In Europe a range of segregation studies can be found in the North, West and South, but hardly any in Central Eastern Europe – a region where the major economic and political changes induced by the demise of socialism in 1989 contributed to new social divisions and related spatial patterns. However, these changes have not been uniform and have resulted in context-specific outcomes. Relying on data on the socio-occupational structure of the population from the National Census 2002 at the census tract scale, this article explores the levels and patterns of social segregation in three major Polish cities: Łódź, Cracow and Warsaw, urban areas that reflect divergent paths of more and less successful post-socialist transformations. This contribution concludes that, more than a decade after the demise of socialism, census tracts still generally contained populations that were heterogeneous with regard to socio-occupational status and that socioeconomic transformations in Poland and the social toll these processes involved have not yet been fully translated into intra-urban spaces.
Framing neoliberal urbanism: Translating ‘commonsense’ urban policy across the OECD zone
Authors: Theodore Nik , Peck Jamie
Published: December 2011

The paper explores the evolution of urban policy discourses among advanced industrial nations in the period since the early 1980s, by way of a case study of the OECD (Organisation for Economic Co-operation and Development). The OECD, it is argued, has provided an arena for the consolidation of a particular form of neoliberal urbanism, conceived here as a mutating policy frame. As a consensus-finding organization, the OECD is more of a mediator than a unilateral driver of policy conventions. It is not a site of hard-edged or radical policy innovation, but seeks to define a ‘common ground’ in the form of a positive policy consensus. As such, the OECD’s coordinative discourse both reflects and refracts a particular reading of the ‘soft center’ of the urban policy consensus, revealing how (far) this has moved since the early 1980s. Hardly preordained, this transnational mode of neoliberal urbanism has been a constructed project, subject to significant adaption and evolution.
The Challenge of Governing a Post-Conflict City
Authors: Pathak Pushpa
Published: December 2011

Following good urban governance practices and realizing sustainable urbanization goals are major development challenges experienced in most developing countries. This challenge is even more acute in the post-conflict and transition countries. This article on Kabul illustrates this point and presents some of the key governance challenges faced by the city, such as: phenomenal rate of population growth; a large proportion of the city being informally developed; massive damage to the city infrastructure; poor service levels; and weak institutions unable to deal with the present challenge of reconstructing and developing the city. The article also identifies some of the critical steps to be taken for sustainable urban development, which are: ( i) enactment of the revised Municipal Law of Afghanistan; ( ii) clarification of the institutional authority and responsibilities of the concerned organization; ( iii) resolving municipal boundary and overlapping spatial jurisdiction issues; ( iv) holding local government elections; ( v) estab-lishing a more decentralized local governance framework; ( vi) finalization and approval of the Kabul City Master Plan; ( vii) strengthening the municipal revenue enhancement programme; ( viii) implementing a comprehensive human resource development programme at Kabul municipality; ( ix) institutionalizing by law active public participation in local governance and management; ( x) formulating a city-level strat-egy and action plan for informal settlement regularization and upgrading; ( xi) setting up an effective inter-agency city development coordination mechanism led by the Mayor of Kabul; and ( xii) establishing an appropriate metropolitan area development coordination body.
Angiotensin II signalling and calcineurin in cardiac fibroblasts: differential effects of calcineurin inhibitors FK506 and cyclosporine A
Authors: White Michel , Montezano Augusto C. , Touyz Rhian M.
Published: December 2011

Introduction: Cardiac remodelling is controlled by complex systems, including activation of the renin-angiotensin system (RAS) and signalling through MAP kinases and Ca2+-activated calcineurin. Whether Ang II, which increases [Ca2+]i and stimulates MAP kinases, mediates myocardial effects through calcineurin-dependent pathways remain unclear. We investigated effects of two calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus (FK506) (10-10-10-6 mol/L, 20 mins) on activation of MAP kinases and on growth, pro-fibrotic and pro-inflammatory responses in Ang II-stimulated rat cardiac fibroblasts.

Methods and Results: Ang II increased phosphorylation of ERK1/2 and p38MAPK (1.5-1.8-fold, p<0.05) without effect on JNK. FK506, but not CsA, attenuated Ang II-stimulated MAP kinase activation. Molecular indices of cell growth (proliferating cell nuclear antigen (PCNA)), fibrosis (fibronectin, pro-collagen) and inflammation (iNOS), were upregulated by Ang II (12 hrs). FK506 and CsA inhibited PCNA effects. Ang II-induced pro-fibrotic and pro-inflammatory responses were inhibited by CsA. Ang II receptors, AT1R and AT2R, were not influenced by calcineurin inhibitors. Our data indicate differential calcineurin inhibitor sensitivity of MAP kinases and cellular responses in Ang II-stimulated fibroblasts. p38MAP kinase and ERK1/2 are regulated in a FK506-sensitive manner, whereas fibrosis and inflammation are CsA-sensitive. Cell proliferation is inhibited by both FKC506 and CsA. These are post-receptor phenomena, since AT1R and AT2R status was unaltered by treatment.

Conclusions: Our findings identify an important role for calcineurin in MAP kinase/growth/pro-fibrotic/pro-inflammatory signalling by Ang II in cardiac fibroblasts. Although both FK506 and CsA inhibit calcineurin, they exert differential effects on molecular and cellular responses. Such differences may contribute to variable clinical responses of these agents.
Coins to Flint: John Evans and the Numismatic Moment in the History of Archaeology
Authors: Schlanger Nathan
Published: December 2011

John Evans was a key actor in the establishment of high human antiquity in 1859, and his pioneering role in launching the study of ancient stone implements is still celebrated today. However, scholars have overlooked the fact that Evans actually forged this contribution by shifting practices and preoccupations from coins to flint, from one well-established antiquarian domain in which he excelled, to another, new and as yet untested, domain. While providing relevant information on Evans' numismatics, this article shows how these transfers bear successively on the documentation of stone implements (terminology, descriptions, illustrations), their authentication (with regards to frauds and experimentation) and indeed their interpretation (the identification and explanation of their formal variability). Besides serving as an instructive historical case in ‘trans-disciplinarity’, the recognition of this initial numismatic imprint on the study of stone tools also has several consequences for current practices and interpretations in Palaeolithic archaeology.
Bronze Age Ceramic Economy: The Benta Valley, Hungary
Authors: Earle Timothy , Kreiter Attila , Klehm Carla , Ferguson Jeffrey , Vicze Magdolna
Published: December 2011

We describe the Bronze Age ceramic economy of the Benta Valley in Hungary. In the Bronze Age, long-distance trade in metals, metal objects, and other specialty items became central to expansive prestige goods exchange through Europe. Was that exchange in wealth, however, linked to broader developments of an integrated market system? The beginnings of market systems in prehistory are poorly understood. We suggest a means to investigate marketing by studying the changing ceramic economy of a region, rather than at a single site. Analysis of the ceramic inventory collected as part of the Benta Valley Project strongly suggests that, although ceramic production was quite sophisticated and probably specialized, exchange was highly localized (mostly within 10 km) and conducted through personalized community networks. Our ceramic study used three progressively finer-scaled analyses: inventorying ceramic forms and decoration to evaluate consumption patterns, petrographic analysis to describe manufacturing sequences, and instrumental neutron activation analysis (INAA) to describe exchange. We conclude that, based on present evidence, market systems had not developed in Hungary during the Bronze Age.
Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project
Authors: Hooper Richard , Burney Peter , Vollmer William M. , McBurnie Mary Ann , Gislason Thorarinn , Tan Wan C. , Jithoo Anamika , Kocabas Ali , Welte Tobias , Buist A. Sonia
Published: December 2011

Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020.

The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis.

Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35–1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37–0.67), level of education completed (OR 0.76, 95% CI 0.67–0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42–3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05–1.47), tuberculosis (OR 1.78, 95%CI 1.17–2.72) and a family history of COPD (OR 1.50, 95% CI 1.19–1.90).

Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.
A breath test for malignant mesothelioma using an electronic nose
Authors: Chapman Eleanor A. , Thomas Paul S. , Stone Emily , Lewis Craig , Yates Deborah H.
Published: December 2011

Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity.

20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case–control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction.

10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases.

Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.
Bronchoalveolar lavage pepsin in acute exacerbation of idiopathic pulmonary fibrosis
Authors: Lee J.S. , Song J.W. , Wolters P.J. , Elicker B.M. , King T.E. , Kim D.S. , Collard H.R.
Published: December 2011

Some patients with idiopathic pulmonary fibrosis experience acute exacerbations in their respiratory status leading to substantial morbidity and mortality. Occult aspiration of gastric contents has been proposed as one possible mechanism leading to these acute exacerbations. We sought to determine whether pepsin, a marker of gastric aspiration, is elevated in bronchoalveolar lavage fluid obtained from patients during acute exacerbation of idiopathic pulmonary fibrosis, compared with that obtained in stable disease.

Lavage samples were obtained in a case–control study of well-characterised patients. Acute exacerbation was defined using standard criteria. Levels of lavage pepsin were compared in cases and controls, and were correlated with clinical features and disease course.

24 cases with acute exacerbations and 30 stable controls were identified. There were no significant differences in baseline demographics between the two groups. Pepsin level was an indicator of acute exacerbation status (p=0.04). On average, pepsin appeared higher in patients with acute exacerbations compared with stable controls. This difference was driven by a subgroup of eight patients (33%) with pepsin levels ≥70 ng·mL−1. Pepsin level was not an independent predictor of survival time.

These results suggest occult aspiration may play a role in some cases of acute exacerbation of idiopathic pulmonary fibrosis.
The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis
Authors: Lee Peilin , Douglas Neil J. , Riha Renata L.
Published: December 2011

Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension. Increased angiotensin-converting enzyme (ACE) activity may be a possible promoting mechanism with different ACE insertion/deletion (I/D) genotypes influencing this activity. Studies investigating the association of ACE I/D polymorphisms with OSA have shown conflicting results. We aimed to undertake a meta-analysis of existing studies exploring the association of ACE I/D polymorphisms with the risk of OSA and hypertension.

10 studies were included in a random effects meta-analysis, comprising 1,227 OSA subjects and 1,227 controls.

The effect size was measured using the odds ratio. The risk of having OSA in carriers of the D allele was 0.92 (95% CI 0.69–1.23). There was statistically significant heterogeneity across the studies (I2=42%, p=0.08 and I2=74%, p<0.0001 for genotype and allele frequency, respectively). The association of D allele frequency with the risk of OSA remained nonsignificant after stratification based on ethnicity, source of population sample, and the presence of hypertension. Subgroup analysis failed to show any influence of genotype and allele frequency on OSA severity.

This meta-analysis revealed no association between the ACE I/D polymorphisms and OSA susceptibility.
Stanford Seven-Day Physical Activity Recall questionnaire in COPD
Authors: Garfield Benjamin E. , Canavan Jane L. , Smith Cayley J. , Ingram Karen A. , Fowler Ria P. , Clark Amy L. , Polkey Michael I. , Man William D-C.
Published: December 2011

Quantification of daily physical activity is of clinical interest in chronic obstructive pulmonary disease (COPD). Objective measures using activity monitors may take several days to obtain reliable results. The aim of our study was to evaluate the Stanford Seven-Day Physical Activity Recall questionnaire (PAR) against the SenseWear armband (SWA) and compare its validity with three other physical activity questionnaires.

43 COPD patients wore the SWA for 7 days. Patients completed the PAR, Baecke, Physical Activity Scale for the Elderly (PASE) and Zutphen questionnaires. Spearman rank correlation, intraclass correlation coefficients (ICC) and receiver-operating characteristics (ROC) curves were used to assess the relationship between the questionnaires and SWA.

Assessed by PAR, time spent at ≥3.0 metabolic equivalents (METs) correlated significantly (r=0.54, p<0.001) with equivalent measures from SWA, with an ICC of 0.40. No relationship was seen between the other questionnaires and the SWA. The PAR predicted active patients (≥30 min at ≥3.0 METs or a physical activity level (PAL) ≥1.55) and very inactive patients (PAL <1.40) with an area under ROC curve of 0.83, 0.77 and 0.70, respectively.

While the PAR did not measure physical activity sufficiently accurately to make individual recommendations, it was able to identify COPD patients at extremes of the physical activity spectrum, potentially reducing the number of patients requiring direct measurement.
Knowledge of tuberculosis-treatment prescription of health workers: a systematic review
Authors: van der Werf Marieke J. , Langendam Miranda W. , Huitric Emma , Manissero Davide
Published: December 2011

Treating tuberculosis (TB) patients with inappropriate treatment regimens can lead to treatment failure and, thus, patients who have not been cured and/or to the development of (multi)-drug resistance. A systematic review was performed to assess the knowledge of appropriate TB drug regimens among all categories of healthcare workers (HCWs).

In January 2011, MEDLINE, EMBASE and other databases were searched for relevant articles. Observational studies published as of the year 2000 that assessed HCW knowledge of TB treatment were selected. A treatment regimen, drug dosage or treatment duration was considered inappropriate if it was not recommended by national guidelines or by the World Health Organization (WHO).

Of 1,896 studies, 31 were included from 14 different countries. No study was performed in Europe. In all studies, HCWs with inappropriate knowledge of treatment regimens (8–100%) or treatment duration (5–99%) were observed. The few studies providing detailed data showed that HCWs mainly reported giving treatment regimens with too many drugs and for too long. Knowledge of appropriate doses was also insufficient in most studies.

The available studies show that there is a lack of knowledge of national or international TB treatment guidelines and recommendations. Generalisation of the findings to other settings and countries should be done with caution.
Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia
Authors: Del Rio Rodrigo , Moya Esteban A. , Parga María J. , Madrid Carlos , Iturriaga Rodrigo
Published: December 2011

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIH-induced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA.

We studied the effects of ibuprofen (40 mg·kg−1·day−1) on immunohistochemical interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O2(12 episodes·h−1, 8 h·day−1) or kept under sham condition.

CIH increased CB TNF-α and IL-1β and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation.

Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways.
Age- and height-based prediction bias in spirometry reference equations
Authors: Quanjer Philip H. , Hall Graham L. , Stanojevic Sanja , Cole Tim J. , Stocks Janet
Published: December 2011

Prediction bias in spirometry reference equations can arise from combining equations for different age groups, rounding age or height to integers or using self-reported height.

To assess the bias arising from these sources, the fit of 13 prediction equations was tested against the Global Lungs Initiative (GLI) dataset using spirometric data from 55,136 healthy Caucasians (54% female). The effects on predicted values of using whole-year ageversusdecimal age, and of a 1% bias in height, were quantified.

In children, the prediction bias relative to GLI ranged from -22% to +17%. Switching equations at 18 yrs of age led to biases of between -846 (-14%) and +1,309 (+38%) mL. Using age in whole years rather than decimal age introduced biases from -8% to +7%, whereas a 1% overestimation of height introduced bias that ranged from +1% to +40%. Bias was greatest in children and adolescents, and in short elderly subjects.

Using a single spirometry equation applicable across all ages and populations reduces prediction bias. Measuring and recording age and height accurately are also essential if bias is to be minimised.
Antigen-specific multifunctional T-cells in sarcoidosis patients with Löfgren’s syndrome
Authors: Wikén Maria , Ostadkarampour Mahyar , Eklund Anders , Willett Matthew , Chen Edward , Moller David , Grunewald Johan , Wahlström Jan
Published: December 2011

Sarcoidosis is a granulomatous disease of unknown aetiology, mainly affecting the lungs. Recently, T-cell responses towards a specific mycobacterial protein, catalase–peroxidase (mKatG), were observed in sarcoidosis patients.

Bronchoalveolar lavage (BAL) fluid and peripheral blood were obtained from a total of 23 sarcoidosis patients, of whom 13 had Löfgren’s syndrome and lung accumulations of T-cell receptor AV2S3+ T-cells. Using six-colour flow cytometry in combination with intracellular cytokine staining, T-cell subsets were studied with regard to interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin-2 production, after stimulation with mKatG orMycobacterium tuberculosispurified protein derivate (PPD).

Stimulation with mKatG resulted in higher simultaneous IFN-γ and TNF production, but less single IFN-γ production, from total BAL fluid CD4+ T-cells of Löfgren’s syndrome patients, when compared with non-Löfgren’s patients. In contrast, PPD stimulation gave rise to largely similar cytokine responses in both patient subgroups. Furthermore, mKatG stimulated higher IFN-γ production in BAL fluid and blood AV2S3+ T-cells than AV2S3- T-cells, whereas the opposite was seen in BAL fluid with PPD stimulation.

Our finding that patients with Löfgren’s syndrome exhibited a more pronounced multifunctional cytokine profile (simultaneous IFN-γ and TNF production) towards the mycobacterial protein mKatG may help to explain the distinct disease presentation in this patient subgroup.
Theileria annulata-transformed cell lines are efficient antigen-presenting cells for in vitro analysis of CD8 T cell responses to bovine herpesvirus-1
Authors: Hart Jane , MacHugh Niall D , Morrison W Ivan
Published: December 2011

Continuously growing cell lines infected with the protozoan parasiteTheileria annulatacan readily be established by in vitro infection of leukocytes with the sporozoite stage of the parasite. The aim of the current study was to determine whether such transformed cell lines could be used as antigen presenting cells to analyse the antigenic specificity of bovine CD8 T cell responses to viral infections. Bovine herpes virus 1 (BHV-1), which is known to induce CD8 T cell responses, was used as a model.T. annulata- transformed cells were shown to express high levels of CD40 and CD80 and were susceptible to infection with BHV-1, vaccinia and canarypox viruses. The capacity of the cells to generate antigen-specific CD8 T cell lines was initially validated using a recombinant canarypox virus expressing a defined immunodominantT. parvaantigen (Tp1). AutologousT. annulata-transformed cells infected with BHV-1 were then used successfully to generate specific CD8 T cell lines and clones from memory T cell populations of BHV-1-immune animals. These lines were BHV-1-specific and class I MHC-restricted. In contrast to previous studies, which reported recognition of the glycoproteins gB and gD, the CD8 T cell lines generated in this study did not recognise these glycoproteins. Given the ease with whichT. annulata-transformed cell lines can be established and maintained in vitro and their susceptibility to infection with poxvirus vectors, these cell lines offer a convenient and efficient in vitro system to analyse the fine specificity of virus-specific CD8 T cell responses in cattle.
Cost sensitive hierarchical document classification to triage PubMed abstracts for manual curation
Authors: Seymour Emily , Damle Rohini , Sette Alessandro , Peters Bjoern
Published: December 2011

Background

The Immune Epitope Database (IEDB) project manually curates information from published journal articles that describe immune epitopes derived from a wide variety of organisms and associated with different diseases. In the past, abstracts of scientific articles were retrieved by broad keyword queries of PubMed, and were classified as relevant (curatable) or irrelevant (not curatable) to the scope of the database by a Naïve Bayes classifier. The curatable abstracts were subsequently manually classified into categories corresponding to different disease domains. Over the past four years, we have examined how to further improve this approach in order to enhance classification performance and to reduce the need for manual intervention.

Results

Utilizing 89,884 abstracts classified by a domain expert as curatable or uncuratable, we found that a SVM classifier outperformed the previously used Naïve Bayes classifier for curatability predictions with an AUC of 0.899 and 0.854, respectively. Next, using a non-hierarchical and a hierarchical application of SVM classifiers trained on 22,833 curatable abstracts manually classified into three levels of disease specific categories we demonstrated that a hierarchical application of SVM classifiers outperformed non-hierarchical SVM classifiers for categorization. Finally, to optimize the hierarchical SVM classifiers' error profile for the curation process, cost sensitivity functions were developed to avoid serious misclassifications. We tested our design on a benchmark dataset of 1,388 references and achieved an overall category prediction accuracy of 94.4%, 93.9%, and 82.1% at the three levels of categorization, respectively.

Conclusions

A hierarchical application of SVM algorithms with cost sensitive output weighting enabled high quality reference classification with few serious misclassifications. This enabled us to significantly reduce the manual component of abstract categorization. Our findings are relevant to other databases that are developing their own document classifier schema and the datasets we make available provide large scale real-life benchmark sets for method developers.
The MEK2-binding tumor suppressor hDlg is recruited by E-cadherin to the midbody ring
Authors: Gaudet Suzanne , Langlois Marie-Josée , Lue Robert A , Rivard Nathalie , Viel Alain
Published: December 2011

Background

The human homologue of the Drosophila Discs-large tumor suppressor protein, hDlg, is a multi-domain cytoplasmic protein that localizes to the membrane at intercellular junction sites. At both synaptic junctions and epithelia cell-cell junctions, hDlg is known to recruit several signaling proteins into macromolecular complexes. hDlg is also found at the midbody, a small microtubule-rich structure bridging the two daughter cells during cytokinesis, but its function at this site is not clear.

Results

Here we describe the interaction of hDlg with the activated form of MEK2 of the canonical RAF/MEK/ERK pathway, a protein that is found at the midbody during cytokinesis. We show that both proteins localize to a sub-structure of the midbody, the midbody ring, and that the interaction between the PDZ domains of hDlg and the C-terminal portion of MEK2 is dependent on the phosphorylation of MEK2. Finally, we found that E-cadherin also localizes to the midbody and that its expression is required for the isoform-specific recruitment of hDlg, but not activated MEK2, to that structure.

Conclusion

Our results suggest that like at other cell-cell junction sites, hDlg is part of a macromolecular complex of structural and signaling proteins at the midbody.
PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae
Authors: Palmeri Antonio , Gherardini Pier Federico , Tsigankov Polina , Ausiello Gabriele , Späth Gerald F , Zilberstein Dan , Helmer-Citterich Manuela
Published: December 2011

Background

Protein phosphorylation modulates protein function in organisms at all levels of complexity. Parasites of the Leishmania genus undergo various developmental transitions in their life cycle triggered by changes in the environment. The molecular mechanisms that these organisms use to process and integrate these external cues are largely unknown. However Leishmania lacks transcription factors, therefore most regulatory processes may occur at a post-translational level and phosphorylation has recently been demonstrated to be an important player in this process. Experimental identification of phosphorylation sites is a time-consuming task. Moreover some sites could be missed due to the highly dynamic nature of this process or to difficulties in phospho-peptide enrichment.

Results

Here we present PhosTryp, a phosphorylation site predictor specific for trypansomatids. This method uses an SVM-based approach and has been trained with recent Leishmania phosphosproteomics data. PhosTryp achieved a 17% improvement in prediction performance compared with Netphos, a non organism-specific predictor. The analysis of the peptides correctly predicted by our method but missed by Netphos demonstrates that PhosTryp captures Leishmania-specific phosphorylation features. More specifically our results show that Leishmania kinases have sequence specificities which are different from their counterparts in higher eukaryotes. Consequently we were able to propose two possible Leishmania-specific phosphorylation motifs.

We further demonstrate that this improvement in performance extends to the related trypanosomatids Trypanosoma brucei and Trypanosoma cruzi. Finally, in order to maximize the usefulness of PhosTryp, we trained a predictor combining all the peptides from L. infantum, T. brucei and T. cruzi.

Conclusions

Our work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at http://phostryp.bio.uniroma2.it