bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the injury risk in frontal impacts of Formula Student cars: a computer-aided engineering analysis
Authors: Davies H C , Gugliotta B
Published: September 2011

This paper presents a parametric study of the injury risk in collisions of race cars designed for the European Formula Student competition. The study is motivated by the fact that only a limited assessment of driver safety is required for this competition. The approach was to model a Formula Student car in a mathematical dynamic model environment. A parametric study was then carried out to investigate the sensitivity of injury to various system variables. These were the crash pulse, the occupant stature, and the occupant posture. These system variables, under close examination, can be changed to alter the occupant kinematics or, in other words, they change the injury risk. The results of the analysis showed that the risk of injury in a frontal impact was dependent on the system variables. The risk of an abbreviated injury scale (AIS)2+ injury was 22.3 per cent in the baseline constant- g test, increasing to 35.2 per cent in the worst case. For AIS3+ the values were 5.1 per cent and 11 per cent, respectively. The study also showed that the occupant restraint conditions in a Formula Student car had a significant influence on the distribution of the injury risk between the body regions. The variation in the injury risk highlighted by this study, both in absolute terms and in the distribution between the body regions, showed that there are limitations to the use of vehicle kinematics in their current guise as a predictive tool for the injury risk. The results of this study represent a significant step in the understanding of the injury risk in a Formula Student frontal impact.
A Systematic Review of Endoglin Gene Expression in Preeclampsia
Authors: Bell Mandy J. , Conley Yvette P.
Published: September 2011

Objective:

To synthesize scientific literature that addresses the role of endoglin (ENG) gene expression in preeclampsia (PE).

Data sources:

A literature search of PubMed and Ovid MEDLINE was conducted using the keywords endoglin, gene, and preeclampsia. Restrictions included English language and humans. Additional articles were identified/selected for evaluation via PubMed e-mail updates (keywords: endoglin and preeclampsia) and review of article reference lists obtained from the search.

Study selection:

The initial 14 abstracts retrieved from the literature search were reviewed and 9 studies were selected for evaluation. Review articles and studies not addressing ENG expression (messenger RNA [mRNA] level) in the context of PE were excluded. An additional six articles were selected from PubMed e-mail updates and reference lists.

Data extraction:

Data related to study objective, design, setting, subject information, phenotype, tissue type, data collection method, statistics, and results were extracted.

Data synthesis:

Regardless of PE definition, ancestral background, gene expression analysis method, tissue type, and time of specimen collection, endoglin appears to play a role in PE development. Moreover, results suggest that a variety of biological mechanisms have the ability to modulate ENG expression in PE, demonstrating the potential complexity associated with endoglin's role in PE.

Conclusions:

This review article is the first to systematically synthesize evidence related to ENG expression in PE. Findings can be utilized to design future studies that (a) address methodological limitations observed in the reviewed studies and (b) specifically examine why ENG expression levels are altered and address mechanisms explaining how these alterations are involved in PE development.
Multiple Sclerosis Severity Scale and whole-brain N-acetylaspartate concentration for patients’ assessment
Authors: Rigotti DJ , Gass A , Achtnichts L , Inglese M , Babb JS , Naegelin Y , Hirsch J , Amann M , Kappos L , Gonen O
Published: September 2011

Background: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking.

Objective: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients’ disease course.

Methods: The MSSS and average WBNAA loss rate (ΔWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a ‘benign’ disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were ‘non-benign’: EDSS score higher than 3.0.

Results: The two cohorts were indistinguishable in age and disease duration. Benign patients’ EDSS and MSSS (2.1 ± 0.7, 1.15 ± 0.60) were significantly lower than non-benign (4.6 ± 1.0, 3.6 ± 1.2; both p < 10−4). Their respective average ΔWBNAA, 0.10 ± 0.16 and 0.11 ± 0.12 mM/year, however, were not significantly different ( p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, ΔWBNAA is only sensitive (92.6%) but not specific (2.9%).

Conclusion: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that ‘benign’ MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.
Simvastatin improves final visual outcome in acute optic neuritis: a randomized study
Authors: Tsakiri Anna , Kallenbach Klaus , Fuglø Dan , Wanscher Benedikte , Larsson Henrik , Frederiksen Jette
Published: September 2011

Background: In recent years, small-scale clinical trials have indicated that statins or 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors exert pleiotropic immunomodulatory effects, with potential therapeutic implications in multiple sclerosis (MS).

Objective: To investigate whether simvastatin treatment (80 mg daily for 6 months) in patients with optic neuritis (ON) had a beneficial effect on visual outcome and on brain MRI.

Methods: Sixty-four patients with acute ON were randomized to simvastatin treatment ( n = 32) or placebo ( n = 32) for 6 months. None of the patients had been on immunosuppressive therapy for 6 months prior to inclusion or treated with steroids from symptom onset. Contrast sensitivity (Arden plates), visual acuity, colour perception, visual evoked potentials (VEP) – latency and amplitude, Visual Analogue Scale (VAS) score, and gadolinium enhancing and T2 lesions on brain MRI were evaluated at screening visit, day 14 (except brain MRI), day 90 and day 180.

Results: Simvastatin had a beneficial effect on VEP in both latency ( p = 0.01) and amplitude ( p = 0.01), a borderline effect on the Arden score ( p = 0.06) and VAS ( p = 0.04), and no effect on brain MRI or on relapse rate between the groups.

Conclusion: This study provides Class I evidence that simvastatin 80 mg daily is well tolerated and possibly effective in patients with acute ON.
International students’ emotional security and dignity in an Australian context: An aspect of psychological well-being
Authors: Tananuraksakul Noparat , Hall David
Published: September 2011

This article explores non-native English-speaking students’ emotional security and dignity responses to their English language proficiency in an Australian context. Confidence is a source of emotional security bolstering dignity. Without it, students lack emotional security, diminishing their dignity when communicating with culturally different others. Emotional security and dignity have a synergistic relationship, in that lack of confidence emotionally threatens one’s face, identity and dignity. The study offers insights that help us to understand how international students’ psychological well-being is affected by English performance.
Enhancing international students’ experiences: An imperative agenda for universities in the UK
Authors: Ramachandran Narayanan T.
Published: September 2011

The role of international students as catalysts for internationalization and related reforms in the UK higher education sector is increasing. With the growing number of international students, administrators and academics are identifying ways to enable international students to adapt to the UK environment and enhance their experiences as students. This article examines the academic and other social problems that international students who pursue programmes offered by the universities in the UK encounter. It also suggests mechanisms that universities may adopt so that international students have a smooth academic progression and a comfortable social life. Describing the roles of different stakeholders in supporting international students, and the need to create a university-wide awareness of the importance of the presence of the international students in the university campus, the article suggests how universities may track the performance of drivers that foster the experiences of international students.
Brain Glutamate Levels Are Decreased in Alzheimer’s Disease
Authors: Fayed Nicolas , Modrego Pedro J. , Rojas-Salinas Guillermo , Aguilar Keyla
Published: September 2011

Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS) and is involved in the pathophysiology of Alzheimer’s disease (AD) in which there is an increased excitotoxicity. Biochemical composition of living tissues including the levels of Glu was analyzed by magnetic resonance spectroscopy (MRS). Previous reports point to decreased levels of Glu in AD. As Glu plays an important role in memory, we hypothesize that Glu levels are decreased in patients with AD when compared with controls. A consecutive sample of 30 patients with mild-to-moderate AD underwent H-MRS with the voxel placed in the bilateral posterior cingulate gyrus. For comparison purposes, we carried out the same technique in 68 patients with mild cognitive impairment (MCI) and in 26 controls. The healthy controls had higher metabolite levels of N-acetyl-aspartate (NAA) than patients with MCI and AD. In turn, patients with MCI and the controls had higher levels of Glu than in patients with AD. The differences were significant in the analysis of variance (ANOVA) test model corrected for age. In the post hoc analysis, the most remarkable differences were seen between patients with AD and the rest (patients with MCI and the controls). In AD, the levels of Glu and NAA are decreased in comparison with MCI and normality, which reflects loss of neurons.
Spinal Reflex Activity
Authors: Hubli Michèle , Dietz Volker , Bolliger Marc
Published: September 2011

Background. Alterations in the function of spinal neuronal circuits underlying locomotion after a spinal cord injury (SCI) are associated with changes in the behavior of spinal reflexes (SRs) in both rats and humans. In healthy subjects, the SR consists of a dominant early reflex component, whereas in chronic, severely affected SCI subjects, a later component dominates. Objective. The aim of this study was to investigate the relationship between SR behavior and walking ability in para-/tetraplegic subjects. Method. The SR was evoked by nonnoxious tibial nerve stimulation. Walking ability was assessed by functional tests and questionnaires. Results. There was a correlation between walking ability and SR behavior in chronic SCI: Severely affected SCI subjects unable to walk showed dominant late SR components, whereas in ambulatory SCI subjects an early SR component dominated. A functional training with an improvement of locomotor ability was accompanied by both a shift from a dominant to a smaller late and the appearance of an early SR component. Conclusions. Our findings indicate that SR can serve as a marker for the locomotor ability of SCI subjects. Neuronal plasticity exploited by a functional training is reflected in both an improvement of locomotor ability and a change in balance of SR components toward the early SR component.
Using cure models and multiple imputation to utilize recurrence as an auxiliary variable for overall survival
Authors: Conlon Anna SC , Taylor Jeremy MG , Sargent Daniel J , Yothers Greg
Published: September 2011

Background Intermediate outcome variables can often be used as auxiliary variables for the true outcome of interest in randomized clinical trials. For many cancers, time to recurrence is an informative marker in predicting a patient's overall survival outcome and could provide auxiliary information for the analysis of survival times.

Purpose To investigate whether models linking recurrence and death combined with a multiple imputation procedure for censored observations can result in efficiency gains in the estimation of treatment effects and be used to shorten trial lengths.

Methods Recurrence and death times are modeled using data from 12 trials in colorectal cancer. Multiple imputation is used as a strategy for handling missing values arising from censoring. The imputation procedure uses a cure model for time to recurrence and a time-dependent Weibull proportional hazards model for time to death. Recurrence times are imputed, and then death times are imputed conditionally on recurrence times. To illustrate these methods, trials are artificially censored 2 years after the last accrual, the imputation procedure implemented, and a log-rank test and Cox model used to analyze and compare these new data with the original data.

Results The results show modest, but consistent gains in efficiency in the analysis using the auxiliary information in recurrence times. Comparison of analyses show the treatment effect estimates and log-rank test results from the 2-year censored imputed data to be in between the estimates from the original data and the artificially censored data, indicating that the procedure was able to recover some of the lost information due to censoring.

Limitations The models used are all fully parametric, requiring distributional assumptions of the data.

Conclusions The proposed models may be useful in improving the efficiency in estimation of treatment effects in cancer trials and shortening trial length.
Challenges in the design and analysis of non-inferiority trials: a case study
Authors: Durkalski Valerie , Silbergleit Robert , Lowenstein Daniel
Published: September 2011

Background The literature on the design, conduct, and analysis of non-inferiority trials is continuously evolving. Several design issues continue to be researched including the choice of active control, choice of non-inferiority margin, and optimal analytic approaches. To date, there has been relatively little in the literature documenting actual experiences with implementing available methodology for non-inferiority trials.

Purpose This article serves as a case study and highlights some of the challenges encountered in the design of a Phase III non-inferiority trial in status epilepticus that is being conducted under a Food and Drug Administration Investigational New Drug Application (IND).

Methods The IND application was put on clinical hold by the Food Drug and Administration due to concerns with the design. Specifically, support for theactive control, non-inferiority margin, and overall interpretability of trial results were questioned, and a recommendation was made to consider a superiority design. The authors describe their interactions with the Food Drug and Administration and their application of available methods and approaches to address these concerns.

Results The investigators’ response to the clinical hold provided detailed information to support the conduct of a non-inferiority trial. The study team received Food Drug and Administration approval to initiate the trial in October 2008. The trial enrollment began in June 2009 and is being conducted by roughly 800 paramedic units in over 40 Emergency Medicine Service systems across the United States.

Limitations There is still a great deal of methodological research needed to fully understand the application and impact of the non-inferiority trial design.

Conclusions It is evident that non-inferiority trials have an important place in clinical trial design and analysis. These trials may be the only way and only opportunity to answer certain questions; so, they must be designed and conductedwith rigor. This case study is an attempt to share our experiences in implementation.
The effect of blocking radial abduction on palmar abduction strength of the thumb
Authors: Nallakaruppan V. , Tung E. Y. , Sebastin S. J. , Karjalainen T. , Peng Y. P.
Published: September 2011

The measurement of palmar abduction strength of the thumb (PAST) is often used as a research tool to provide an objective assessment of thenar muscle function in patients with carpal tunnel syndrome (CTS). The purpose of this study is to determine the effect of blocking radial abduction on PAST in a normal population. PAST was measured for both hands of 100 healthy volunteers in two positions. In the first position a vertical board was placed perpendicular to the radial border of the hand to block radial abduction, and in the second position PAST was measured without the board. Men had greater PAST. There was no difference in PAST between the dominant and non-dominant hand for both men and women, when a vertical board was used. Without the board, the values were significantly greater in the dominant hand. Radial abduction should be blocked during measurement of PAST.
Role innovation through employee social networks
Authors: Aime Federico , Dyne Linn Van , Petrenko Oleg V.
Published: September 2011

We theorize that the location of individual actors in the context of the larger social network within the organization has important but to date overlooked implications for employee role innovations. Complementing past research that places primary emphasis on individual predictors of role innovations, we developed arguments about the nature of basic characteristics of the social structure (the nature of distal and proximal ties) as resources that provide employees with the potential to be innovative about their roles in ways that enhance job satisfaction and career success.
Modeling Student Motivation and Students’ Ability Estimates From a Large-Scale Assessment of Mathematics
Authors: Zerpa Carlos , Hachey Krystal , van Barneveld Christina , Simon Marielle
Published: September 2011

When large-scale assessments (LSA) do not hold personal stakes for students, students may not put forth their best effort. Low-effort examinee behaviors (e.g., guessing, omitting items) result in an underestimate of examinee abilities, which is a concern when using results of LSA to inform educational policy and planning. The purpose of this study was to explore the relationship between examinee motivation as defined by expectancy-value theory, student effort, and examinee mathematics abilities. A principal components analysis was used to examine the data from Grade 9 students ( n = 43,562) who responded to a self-report questionnaire on their attitudes and practices related to mathematics. The results suggested a two-component model where the components were interpreted as task-values in mathematics and student effort. Next, a hierarchical linear model was implemented to examine the relationship between examinee component scores and their estimated ability on a LSA. The results of this study provide evidence that motivation, as defined by the expectancy-value theory and student effort, partially explains student ability estimates and may have implications in the information that get transferred to testing organizations, school boards, and teachers while assessing students’ Grade 9 mathematics learning.
A zebrafish model of dyskeratosis congenita reveals hematopoietic stem cell formation failure resulting from ribosomal protein-mediated p53 stabilization
Authors: Pereboom Tamara C. , van Weele Linda J. , Bondt Albert , MacInnes Alyson W.
Published: September 2011

Dyskeratosis congenita (DC) is a bone marrow failure disorder characterized by shortened telomeres, defective stem cell maintenance, and highly heterogeneous phenotypes affecting predominantly tissues that require high rates of turnover. Here we present a mutant zebrafish line with decreased expression of nop10, one of the known H/ACA RNP complex genes with mutations linked to DC. We demonstrate that this nop10 loss results in 18S rRNA processing defects and collapse of the small ribosomal subunit, coupled to stabilization of the p53 tumor suppressor protein through small ribosomal proteins binding to Mdm2. These mutants also display a hematopoietic stem cell deficiency that is reversible on loss of p53 function. However, we detect no changes in telomere length in nop10 mutants. Our data support a model of DC whereupon in early development mutations involved in the H/ACA complex contribute to bone marrow failure through p53 deregulation and loss of initial stem cell numbers while their role in telomere maintenance does not contribute to DC until later in life.
Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia
Authors: Walker Aisha L. , Steward Shirley , Howard Thad A. , Mortier Nicole , Smeltzer Matthew , Wang Yong-Dong , Ware Russell E.
Published: September 2011

Hydroxyurea has been shown to be efficacious for the treatment of sickle cell anemia (SCA), primarily through the induction of fetal hemoglobin (HbF). However, the exact mechanisms by which hydroxyurea can induce HbF remain incompletely defined, although direct transcriptional effects and altered cell cycle kinetics have been proposed. In this study, we investigated potential epigenetic and alternative molecular mechanisms of hydroxyurea-mediated HbF induction by examining methylation patterns within the Gγ-globin promoter and miRNA expression within primary CD71+ erythrocytes of patients with SCA, both at baseline before beginning hydroxyurea therapy and after reaching maximum tolerated dose (MTD). Using both cross-sectional analysis and paired-sample analysis, we found that the highly methylated Gγ-globin promoter was inversely correlated to baseline HbF levels, but only slightly altered by hydroxyurea treatment. Conversely, expression of several specific miRNAs was significantly increased after hydroxyurea treatment, and expression of miR-26b and miR-151-3p were both associated with HbF levels at MTD. The significant associations identified in these studies suggest that methylation may be important for regulation of baseline HbF, but not after hydroxyurea treatment, whereas changes in miRNA expression may be associated with hydroxyurea-mediated HbF induction. This study was registered at ClinicalTrials.gov (NCT00305175).
Soluble RAGE is deficient in neutrophilic asthma and COPD
Authors: Sukkar M.B. , Wood L.G. , Tooze M. , Simpson J.L. , McDonald V.M. , Gibson P.G. , Wark P.A.B.
Published: September 2011

The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asthma and chronic obstructive pulmonary disease (COPD).

Bronchial lavage fluid from subjects with moderate-to-severe persistent asthma (n=16) or COPD (n=37), or from healthy controls (n=18), was analysed for neutrophils, total sRAGE, endogenous secretory RAGE (esRAGE), HMGB1 and SAA. We also determined systemic levels of sRAGE in a separate group of asthmatic (n=101) and COPD (n=34) subjects.

Subjects with neutrophilic asthma or COPD had undetectable levels of lung sRAGE, while levels of sRAGE in asthma/COPD without neutrophilia were similar to those in controls. Systemic sRAGE was significantly decreased in subjects with neutrophilic asthma or COPD compared with those without airway neutrophilia. There was significant positive correlation between total sRAGE and esRAGE in the lung and systemically. HMGB1 levels were similar in all subject groups, while SAA was below detectable levels.

Neutrophilic airway inflammation in asthma and COPD is associated with reduced sRAGE.
Adipose tissue in obesity and obstructive sleep apnoea
Authors: Bonsignore M.R. , McNicholas W.T. , Montserrat J.M. , Eckel J.
Published: September 2011

A European Respiratory Society research seminar on “Metabolic alterations in obstructive sleep apnoea (OSA)” was jointly organised in October 2009 together with two EU COST actions (Cardiovascular risk in the obstructive sleep apnoea syndrome, action B26, and Adipose tissue and the metabolic syndrome, action BM0602) in order to discuss the interactions between obesity and OSA.

Such interactions can be particularly significant in the pathogenesis of metabolic abnormalities and in increased cardiovascular risk in OSA patients. However, studying the respective role of OSA and obesity is difficult in patients, making it necessary to refer to animal models orin vitrosystems. Since most OSA patients are obese, their management requires a multidisciplinary approach.

This review summarises some aspects of the pathophysiology and treatment of obesity, and the possible effects of sleep loss on metabolism. OSA-associated metabolic dysfunction (insulin resistance, liver dysfunction and atherogenic dyslipidaemia) is discussed from the perspective of both obesity and OSA in adults and children.

Finally, the effects of treatment for obesity or OSA, or both, on cardio-metabolic variables are summarised. Further interdisciplinary research is needed in order to develop new comprehensive treatment approaches aimed at reducing sleep disordered breathing, obesity and cardiovascular risk.
Validity of an automated telephonic system to assess COPD exacerbation rates
Authors: Bischoff Erik W.M.A. , Boer Lonneke M. , Molema Johan , Akkermans Reinier , van Weel Chris , Vercoulen Jan H. , Schermer Tjard R.J.
Published: September 2011

Current tools for recording chronic obstructive pulmonary disease (COPD) exacerbations are limited and often lack validity testing. We assessed the validity of an automated telephonic exacerbation assessment system (TEXAS) and compared its outcomes with existing tools.

Over 12 months, 86 COPD patients (22.1% females; mean age 66.5 yrs; mean post-bronchodilator forced expiratory volume in 1 s 53.4% predicted) were called once every 2 weeks by TEXAS to record changes in respiratory symptoms, unscheduled healthcare utilisation and use of respiratory medication. The responses to TEXAS were validated against exacerbation-related information collected by observations made by trained research assistants during home visits. No care assistance was provided in any way. Diagnostic test characteristics were estimated using commonly used definitions of exacerbation. Detection rates, compliance and patient preference were assessed, and compared with paper diary cards and medical record review.

A total of 1,824 successful calls were recorded, of which 292 were verified by home visits (median four calls per patient, interquartile range three to five calls per patient). Independent of the exacerbation definition used, validity was high, with sensitivities and specificities between 66% and 98%. Detection rates and compliance differed extensively between the different tools, but were highest with TEXAS. Patient preference did not differ.

TEXAS is a valid tool to assess COPD exacerbation rates in prospective clinical studies. Using different tools to record exacerbations strongly affects exacerbation occurrence rates.
Severity and outcomes of hospitalised community-acquired pneumonia in COPD patients
Authors: Liapikou A. , Polverino E. , Ewig S. , Cillóniz C. , Marcos M.A. , Mensa J. , Bello S. , Martin-Loeches I. , Menéndez R. , Torres A.
Published: September 2011

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with community-acquired pneumonia (CAP). We investigated the impact of COPD on outcomes of CAP patients.

We prospectively studied the clinical presentation of 1,379 patients admitted with CAP during a 4-yr period. A comparative analysis of disease severity and course was performed between 212 patients with COPD, as confirmed by spirometry, and 1,167 non-COPD patients.

COPD patients (mean forced expiratory volume in 1 s 47.7±16.3% predicted) were older and more likely to have previously received antibiotics (37.1%versus28.3%; p<0.01) than those without COPD. They presented with more severe respiratory failure (arterial oxygen tension/inspiratory oxygen fraction 270.4versus287.8; p<0.01) and more severe pneumonia (pneumonia severity index 118.3versus108.5; p<0.001) compared with non-COPD patients. However, COPD patients had less multilobar infiltration (44 (21%)versus349 (30%); p<0.01) and fewer pulmonary complications (24 (14%)versus241 (24%); p<0.01). A total of 89 (6.5%) patients died within 30 days. COPD patients had no significant difference in their 30-day mortality rate compared with non-COPD patients (nine (4.2%) patientsversus81 (7%); p=0.14).

Despite worse clinical presentation, COPD patients had a similar mortality rate compared to non-COPD patients. Previous antibiotic treatment and the decreased incidence of pulmonary complications in COPD may account for these findings.
Quantitative PCR to diagnosePneumocystispneumonia in immunocompromised non-HIV patients
Authors: Mühlethaler K. , Bögli-Stuber K. , Wasmer S. , von Garnier C. , Dumont P. , Rauch A. , Mühlemann K. , Garzoni C.
Published: September 2011

The utility of quantitativePneumocystis jiroveciiPCR in clinical routine for diagnosingPneumocystispneumonia (PCP) in immunocompromised non-HIV patients is unknown.

We analysed bronchoalveolar lavage fluid with real-time quantitativeP. jiroveciiPCR in 71 cases with definitive PCP defined by positive immunofluorescence (IF) tests and in 171 randomly selected patients with acute lung disease. In those patients, possible PCP cases were identified by using a novel standardised PCP probability algorithm and chart review. PCR performance was compared with IF testing, clinical judgment and the PCP probability algorithm.

QuantitativeP. jiroveciiPCR values >1,450 pathogens·mL−1had a positive predictive value of 98.0% (95% CI 89.6–100.0%) for diagnosing definitive PCP. PCR values of between 1 and 1,450 pathogens·mL−1were associated with both colonisation and infection; thus, a cut-off between the two conditions could not be identified and diagnosis of PCP in this setting relied on IF and clinical assessment. Clinical PCP could be ruled out in 99.3% of 153 patients with negative PCR results.

Quantitative PCR is useful for diagnosing PCP and is complementary to IF. PCR values of >1,450 pathogens·mL−1allow reliable diagnosis, whereas negative PCR results virtually exclude PCP. Intermediate values require additional clinical assessment and IF testing. On the basis of our data and for economic and logistical limitations, we propose a clinical algorithm in which IF remains the preferred first test in most cases, followed by PCR in those patients with a negative IF and strong clinical suspicion for PCP.
Matrix metalloproteinases in COPD
Authors: Churg A. , Zhou S. , Wright J.L.
Published: September 2011

There is considerable evidence that matrix metalloproteinases (MMPs) are up- and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smoke-induced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.
COPD is associated with reduced pulmonary interstitial expression of pentraxin-3
Authors: Van Pottelberge G.R. , Bracke K.R. , Pauwels N.S. , Vermassen F.E. , Joos G.F. , Brusselle G.G.
Published: September 2011

Pentraxin (PTX)3 is involved in antimicrobial defence, apoptotic cell clearance and extracellular matrix stability. As these processes are altered in chronic obstructive pulmonary disease (COPD), we aimed to investigate PTX3 expression in patients with this disease.

PTX3 expression was quantified by immunohistochemical staining of lung tissue from never-smokers, smokers without COPD, and in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, II and III–IV. mRNA expression was examined in total lung tissue by quantitative RT-PCR. PTX3 concentration was measured in induced sputum and plasma by ELISA.

PTX3 is mainly localised in the interstitium of the small airways and alveolar walls. There were no significant differences in pulmonary, sputum and plasma PTX3 expression between study groups. However, PTX3 expression in small airways correlated significantly with forced expiratory volume in 1 s (r=0.35, p=0.004). In the alveolar walls, PTX3 expression correlated significantly with carbon monoxide transfer coefficient (r=0.28, p=0.04). In sputum, PTX3 levels were highly correlated with the number of neutrophils. Finally, systemic levels of PTX3 tended to be lower in severe COPD compared with mild COPD.

In COPD, airflow limitation and reduced transfer coefficient for carbon monoxide are associated with lower pulmonary interstitial expression of PTX3.
Significance of connective tissue disease features in idiopathic interstitial pneumonia
Authors: Corte T.J. , Copley S.J. , Desai S.R. , Zappala C.J. , Hansell D.M. , Nicholson A.G. , Colby T.V. , Renzoni E. , Maher T.M. , Wells A.U.
Published: September 2011

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP.

IIP patients undergoing surgical lung biopsy (1979–2005) were studied (nonspecific interstitial pneumonia (NSIP), n=45; idiopathic pulmonary fibrosis, n=56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed usinga priorivariables. The prognostic utility of UCTD, and of this algorithm, was evaluated.

UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21–33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud’s phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14–0.85; p=0.02) independent of IIP severity.

UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.
Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze
Authors: Kusel M.M.H. , Kebadze T. , Johnston S.L. , Holt P.G. , Sly P.D.
Published: September 2011

Severe viral respiratory illnesses and atopy are risk factors for childhood wheezing and asthma. The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with wheeze and asthma persisting into later childhood.

147 children at high atopic risk were followed from birth to age 10 yrs. Data on all respiratory infections occurring in infancy were collected prospectively and viral aetiology ascertained. Atopy was measured by skin prick tests at 6 months, and 2 and 5 yrs. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 yrs of age.

At 10 yrs, 60% of the cohort was atopic, 25.9% had current eczema, 18.4% current asthma and 20.4% persistent wheeze. 35.8% experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life. Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 yrs, were significantly more likely to have persistent wheeze (RR 3.51, 95% CI 1.83–6.70; p<0.001) and current asthma (RR 4.92, 95% CI 2.59–9.36; p<0.001) at 10 yrs.

Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The occurrence of fever during respiratory illnesses is an important marker of risk for wheeze and asthma later in childhood, suggesting it should be measured in prospective studies of asthma aetiology.
Mapping quantitative trait loci for T lymphocyte subpopulations in peripheral blood in swine
Authors: Lu Xin , Liu Jian-Feng , Gong Yuan-Fang , Wang Zhi-Peng , Liu Yang , Zhang Qin
Published: September 2011

Background

Increased disease resistance through improved general immune capacity would be beneficial for the welfare and productivity of farm animals. T lymphocyte subpopulations in peripheral blood play an important role in immune capacity and disease resistance in animals. However, very little research to date has focused on quantitative trait loci (QTL) for T lymphocyte subpopulations in peripheral blood in swine.

Results

In the study, experimental animals consist of 446 piglets from three different breed populations. To identify QTL for T lymphocyte subpopulations in peripheral blood in swine, the proportions of CD4+, CD8+, CD4+CD8+, CD4+CD8-, CD4-CD8+, and CD4-CD8- T cells and the ratio of CD4+:CD8+ T cells were measured for all individuals before and after challenge with modified live CSF (classical swine fever) vaccine. Based on the combined data of individuals from three breed populations, genome-wide scanning of QTL for these traits was performed based on a variance component model, and the genome wide significance level for declaring QTL was determined via permutation tests as well as FDR (false discovery rate) correction. A total of 27 QTL (two for CD4+CD8+, one for CD4+CD8-, three for CD4-CD8+, two for CD4-CD8-, nine for CD4+, two for CD8+, and eight for CD4+:CD8+ ratio) were identified with significance level ofFDR< 0.10, of which 11 were significant at the level ofFDR< 0.05, including the five significant atFDR< 0.01.

Conclusions

Within these QTL regions, a number of known genes having potential relationships with the studied traits may serve as candidate genes for these traits. Our findings herein are helpful for identification of the causal genes underlying these immune-related trait and selection for immune capacity of individuals in swine breeding in the future.
Patient-Oriented Cancer Information on the Internet: A Comparison of Wikipedia and a Professionally Maintained Database
Authors: Rajagopalan Malolan S. , Khanna Vineet K. , Leiter Yaacov , Stott Meghan , Showalter Timothy N. , Dicker Adam P. , Lawrence Yaacov R.
Published: September 2011

The coverage, accuracy, and readability of cancer information on Wikipedia are compared with the patient-orientated National Cancer Institute's Physician Data Query comprehensive cancer database.
Assessment of Perceived Cost to the Patient and Other Barriers to Clinical Trial Participation
Authors: Weckstein Douglas J. , Thomas Christian A. , Emery Ivette F. , Shea Barbara F. , Fleury Alison , White Margaret E. , Chase Elizabeth , Robinson Cindy , Frazier Stacey , Pilar Christine
Published: September 2011

Concerns about adverse effects and random assignment were the most common reasons cited by patients declining trial participation in four community oncology practices in New England.
Results of the ASCO Study of Collaborative Practice Arrangements
Authors: Towle Elaine L. , Barr Thomas R. , Hanley Amy , Kosty Michael , Williams Stephanie , Goldstein Michael A.
Published: September 2011

The supply of oncologists is predicted to fall short of demand in decades to come. Addressing this workforce shortage by employing nonphysician practitioners as a routine part of practice can substantially benefit both patients and providers.
Performing Literary History
Authors: Ritchie Leslie , Fisher Judith W.
Published: September 2011

This article charts the collaborative production of a play designed to show that performing literary history enables students' perception of history as process and performance. The play Before & After highlighted conventions of seventeenth-century prologues, epilogues, and gendered theatrical performance techniques through students' performances and participation in a postproduction survey.
Bending the Gaze
Authors: Comer Denise K.
Published: September 2011

Supervisory class visits — when shaped by transparency, reflection, and reciprocity — are a unique, powerful, and positive mechanism for pedagogic and programmatic growth. Writing programs are especially well situated to transform and model effective supervisory class visits because compositionists have already addressed related challenges regarding writing pedagogies and practices.
La Langue de Coton
Authors: Welch Nancy
Published: September 2011

These papers were given at the 2011 MLA panel on faculty governance. They present the topic's importance in the face of budget crises and institutional pressure.
Reputation and Uncertainty in Online Markets: An Experimental Study
Authors: Rice Sarah C.
Published: September 2011

This paper employs a modified investment game to study how online reputation ratings are assigned, and thus how electronic reputations are formed in transactions where buyers and sellers interact anonymously. Of particular interest are the important questions of how online reputations evolve and how specific reputation information is interpreted by market participants. We vary the level of uncertainty in the transaction environment, and measure the effects of this manipulation on buyers' trust and their subsequent rating behaviors. We distinguish between a reputation mechanism and specific reputation information, finding the former has an association with the overall decision of whether to transact in the marketplace, while the latter shows significance in purchase decisions regarding specific sellers. We also find that aggregate reputation information is weighted differently than singular reputation information. Finally, we show that when reputations are increasingly noisy, buyers are less likely to react negatively to poor ratings and are more likely to give sellers the benefit of the doubt when seemingly uncooperative outcomes occur.
Green approaches to the production of iopamidol
Authors: Anelli Pier Lucio , Brocchetta Marino , Lattuada Luciano , Uggeri Fulvio
Published: September 2011

Iodinated contrast agents, such as iopamidol, are worldwide employed for performing a number of X-ray diagnostic procedures. Every year, thousands of tons of iodinated contrast agents are manufactured for the market with chemical processes that usually employ thionyl chloride. In this paper, we describe two new green approaches to iopamidol that avoid or reduce the use of this noxious reagent.
Investigating Interferences of a Whole-Blood Point-of-Care Creatinine Analyzer: Comparison to Plasma Enzymatic and Definitive Creatinine Methods in an Acute-Care Setting
Authors: Straseski Joely A , Lyon Martha E , Clarke William , DuBois Jeffrey A , Phelan Lois A , Lyon Andrew W
Published: September 2011

BACKGROUND

Although measurement of whole-blood creatinine at the point of care offers rapid assessment of renal function, agreement of point-of-care (POC) results with central laboratory methods continues to be a concern. We assessed the influence of several potential interferents on POC whole-blood creatinine measurements.

METHODS

We compared POC creatinine (Nova StatSensor) measurements with plasma enzymatic (Roche Modular) and isotope dilution mass spectrometry (IDMS) assays in 119 hospital inpatients. We assessed assay interference by hematocrit, pH, pO2, total and direct bilirubin, creatine, prescribed drugs, diagnosis, red blood cell water fraction, and plasma water fraction.

RESULTS

CVs for POC creatinine were 1.5- to 6-fold greater than those for plasma methods, in part due to meter-to-meter variation. Regression comparison of POC creatinine to IDMS results gave a standard error (Sy|x) of 0.61 mg/dL (54 μmol/L), whereas regression of plasma enzymatic creatinine to IDMS was Sy|x 0.16 mg/dL (14 μmol/L). By univariate analysis, bilirubin, creatine, drugs, pO2, pH, plasma water fraction, and hematocrit were not found to contribute to method differences. However, multivariate analysis revealed that IDMS creatinine, red blood cell and plasma water fractions, and hematocrit explained 91.8% of variance in POC creatinine results.

CONCLUSIONS

These data suggest that whole-blood POC creatinine measurements should be used with caution. Negative interferences observed with these measurements could erroneously suggest adequate renal function near the decision threshold, particularly if estimated glomerular filtration rate is determined. Disparity between whole-blood and plasma matrices partially explains the discordance between whole-blood and plasma creatinine methods.
Axial Behaviour of Hollow Core Micropiles Under Monotonic and Cyclic Loadings
Authors: Yehia Abd Elaziz Ahmed , El Naggar M. Hesham
Published: September 2011

The use of hollow core bars in micropiles has greatly increased over the past ten years. Hollow core construction, also termed self drilled, is becoming a popular option because it allows a faster installation processes and ground improvement at the same time. This paper presents a field study on the behaviour of single hollow core micropiles in stiff silty clay deposit. Four hollow core micropiles were installed using an air flushing technique employing large drilling carbide bits. Ten axial tests were conducted on the four micropiles, including three compression tests, two tension monotonic axial tests, four compression cyclic tests, and one tension cyclic axial tests. The results of the full-scale loading tests are presented and analyzed in terms of load displacement curves. The results of the monotonic testing phase showed that the bond strength values (αbond) suggested by the Federal Highway Administration in 2000 for the silty clay deposits may be underestimated when considering hollow core micropiles as type B micropile grouting. The response of the micropiles to cyclic loading is considered satisfactory. No sign of full debonding occurring at the pile-soil interface was observed after 15 load cycles with cyclic load amplitude of 33 % of the micropile design load. The stiffness of most micropiles remained almost constant after the cyclic loading. However, the pile head movement increased after the cyclic loading due to limited strain softening behaviour of the soil deposit occurs at the grout/ground interface. The results showed that the micopile’s performance in stiff clay is not sensitive to minor changes in cyclic load amplitudes, but sensitive to the magnitude and rate of the total applied load.