bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-heparin/platelet factor 4 antibody optical density values and the confirmatory procedure in the diagnosis of heparin-induced thrombocytopenia
Authors: Perry Stephanie L. , Ortel Thomas L. , Whitlatch Nicole L. 
Published: September 2008

SummaryLaboratory testing for heparin-induced thrombocytopenia (HIT) includes the highly sensitive, though less specific, heparin/ platelet factor 4 (PF4) ELISA. A confirmatory test with excess heparin is routinely performed on positive ELISA results to improve test specificity; the significance of a negative confirmatory result is unknown. The aim was firstly to evaluate the clinical utility of the PF4 ELISA confirmatory assay, secondly to examine the relationship between ELISA optical density (OD) value and clinical diagnosis of HIT, and thirdly to assess current practice at a tertiary care medical centre regarding patients with anti-heparin/PF4 antibodies. Patients with anti-heparin/PF4 antibodies detected by commercial ELISA during 2005 were identified. A confirmatory test was performed on positive ELISA results. Patients were labeled confirmatory positive (confirm+) or confirmatory negative (confirm−). Patients were classified as HIT+ (met criteria for HIT), HIT? (HIT possible), and HIT- (did not meet criteria for HIT) utilizing ACCP guidelines. One hundred fifteen patients with anti-heparin/PF4 antibodies were identified. Ninety-eight patients were confirm+;17 were confirm−. The majority of confirm+ patients were HIT+ or HIT?(72%);the majority of confirm− patients were HIT− (81%). Patients who were HIT+/confirm+ had higher ELISA OD values than patients who were HIT?/confirm+ or HIT− /confirm+ (p=0.031, p=0.001). Two confirm− patients were HIT+, one was HIT?; all had high ELISA OD values. Although confirm+ status correlated with clinical HIT, the confirmatory procedure misclassified some patients by yielding a confirm− result despite clinical HIT with high ELISA OD values. Future studies should compare higher ELISA OD values with the confirmatory procedure as strategies to improve ELISA diagnostic specificity for HIT.
Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives
Authors: Østergaard Henrik , Bayer Robert J. , Kalo Matt S. , Kinealy Kyle , Holm Pernille K. , Sørensen Brit B. , Zopf David , Bjørn Søren E. , Stennicke Henning R. 
Published: September 2008

SummaryProphylaxis with 2–4 times weekly dosing of factor (F)VIII or FIX is established as an efficacious and safe treatment in haemophilia. Although prophylaxis is not readily available for the inhibitor patient,recent studies have demonstrated a reduction in bleeding episodes in inhibitor patients treated with daily infusions of FVIIa. In order to develop a treatment option comparable to prophylaxis with FVIII or FIX we looked to PEGylation which is an established method for prolonging the circulatory half-life of proteins. However, due to the numerous interactions of FVIIa with the cell surface,TF,FIX and FX there are limited options for unspecific chemical modification of FVIIa without loss of activity. Consequently, we explored the GlycoPEGylation™ technology for selective PEGylation of the two N-glycans in the FVIIa light chain and protease domain to generate seven specifically modified derivatives with PEG groups ranging from 2 to 40 kDa. These derivatives were evaluated in vitro for their ability to interact with small synthetic substrates as well as key molecules relevant to function in the coagulation pathway. The results demonstrate that modification of FVIIa using glycoPEGylation has only a very limited effect on the hydrolysis S-2288 and FX activation. However, the modification does to some extend alter the ability of FVIIa to interact with TF and more importantly, reduces the rate of ATIII inhibition by up to 50% which could allow for an extended active half-life in circulation.
Prospective validation of the Pulmonary Embolism Severity Index
Authors: Gal Grégoire , Fine Michael J. , Roy Pierre-Marie , Sanchez Olivier , Verschuren Franck , Cornuz Jacques , Meyer Guy , Perrier Arnaud , Righini Marc , Aujesky Drahomir , Donzé Jacques 
Published: September 2008

SummaryPractice guidelines recommend outpatient care for selected patients with non-massive pulmonary embolism (PE), but fail to specify how these low-risk patients should be identified. Using data from U.S. patients, we previously derived the Pulmonary Embolism Severity Index (PESI), a prediction rule that risk stratifies patients with PE. We sought to validate the PESI in a European patient cohort. We prospectively validated the PESI in patients with PE diagnosed at six emergency departments in three European countries. We used baseline data for the rule’s 11 prognostic variables to stratify patients into five risk classes (I-V) of increasing probability of mortality. The outcome was overall mortality at 90 days after presentation.To assess the accuracy of the PESI to predict mortality, we estimated the sensitivity, specificity, and predictive values for low- (risk classes I/II) versus higher- risk patients (risk classes III-V), and the discriminatory power using the area under the receiver operating characteristic (ROC) curve. Among 357 patients with PE, overall mortality was 5.9%, ranging from 0% in class I to 17.9% in class V. The 186 (52%) low-risk patients had an overall mortality of 1.1% (95% confidence interval [CI]: 0.1–3.8%) compared to 11.1% (95% CI: 6.8–16.8%) in the 171 (48%) higher- risk patients. The PESI had a high sensitivity (91%,95% CI: 71–97%) and a negative predictive value (99%, 95% CI: 96–100%) for predicting mortality. The area under the ROC curve was 0.78 (95% CI:0.70–0.86). The PESI reliably identifies patients with PE who are at low risk of death and who are potential candidates for outpatient care. The PESI may help physicians make more rational decisions about hospitalization for patients with PE.
Omics meets hypothesis-driven research
Authors: Tissot Jean-Daniel , Farmer Pierre , Mariotti Agnese , Rüegg Curzio 
Published: September 2008

SummaryThe emergence of omics technologies allowing the global analysis of a given biological or molecular system, rather than the study of its individual components,has revolutionized biomedical research, including cardiovascular medicine research in the past decade. These developments raised the prospect that classical,hypothesis-driven,single gene-based approaches may soon become obsolete. The experience accumulated so far, however, indicates that omic technologies only represent tools similar to those classically used by scientists in the past and nowadays, to make hypothesis and build models, with the main difference that they generate large amounts of unbiased information.Thus,omics and classical hypothesis-driven research are rather complementary approaches with the potential to effectively synergize to boost research in many fields, including cardiovascular medicine. In this article we discuss some general aspects of omics approaches, and review contributions in three areas of vascular biology, thrombosis and haemostasis, atherosclerosis and angiogenesis, in which omics approaches have already been applied (vasculomics).
Myeloproliferative disorders
Authors: Levine Ross L. , Gilliland D. Gary 
Published: September 2008

Abstract
In 1951 William Dameshek classified polycythemia vera (PV), essential thombocytosis (ET), and primary myelofibrosis (PMF) as pathogenetically related myeloproliferative disorders (MPD). Subsequent studies demonstrated that PV, ET, and PMF are clonal disorders of multipotent hematopoietic progenitors. In 2005, a somatic activating mutation in the JAK2 nonreceptor tyrosine kinase (JAK2V617F) was identified in most patients with PV and in a significant proportion of patients with ET and PMF. Subsequent studies identified additional mutations in the JAK-STAT pathway in some patients with JAK2V617F− MPD, suggesting that constitutive activation of this signaling pathway is a unifying feature of these disorders. Although the discovery of mutations in the JAK-STAT pathway is important from a pathogenetic and diagnostic perspective, important questions remain regarding the role of this single disease allele in 3 related but clinically distinct disorders, and the role of additional genetic events in MPD disease pathogenesis. In addition, these observations provide a foundation for development of small molecule inhibitors of JAK2 that are currently being tested in clinical trials. This review will discuss our understanding of the pathogenesis of PV, ET, and PMF, the potential role of JAK2-targeted therapy, and the important unanswered questions that need to be addressed to improve clinical outcome.
Phase III Study, V-15-32, of Gefitinib Versus Docetaxel in Previously Treated Japanese Patients With Non–Small-Cell Lung Cancer
Authors: Maruyama Riichiroh , Nishiwaki Yutaka , Tamura Tomohide , Yamamoto Nobuyuki , Tsuboi Masahiro , Nakagawa Kazuhiko , Shinkai Tetsu , Negoro Shunichi , Imamura Fumio , Eguchi Kenji , Takeda Koji , Inoue Akira , Tomii Keisuke , Harada Masao , Masuda Noriyuki , Jiang Haiyi , Itoh Yohji , Ichinose Yukito , Saijo Nagahiro , Fukuoka Masahiro 
Published: September 2008

Purpose This phase III study (V-15-32) compared gefitinib (250 mg/d) with docetaxel (60 mg/m2) in patients (N = 489) with advanced/metastatic non–small-cell lung cancer (NSCLC) who had failed one or two chemotherapy regimens. Methods The primary objective was to compare overall survival to demonstrate noninferiority for gefitinib relative to docetaxel. An unadjusted Cox regression model was used for the primary analysis. Results Noninferiority in overall survival was not achieved (hazard ratio [HR], 1.12; 95.24% CI, 0.89 to 1.40) according to the predefined criterion (upper CI limit for HR ≤ 1.25); however, no significant difference in overall survival (P = .330) was apparent between treatments. Poststudy, 36% of gefitinib-treated patients received subsequent docetaxel, and 53% of docetaxel-treated patients received subsequent gefitinib. Gefitinib significantly improved objective response rate and quality of life versus docetaxel; progression-free survival, disease control rates, and symptom improvement were similar for the two treatments. Grades 3 to 4 adverse events occurred in 40.6% (gefitinib) and 81.6% (docetaxel) of patients. Incidence of interstitial lung disease was 5.7% (gefitinib) and 2.9% (docetaxel). Four deaths occurred due to adverse events in the gefitinib arm (three deaths as a result of interstitial lung disease, judged to be treatment related; one as a result of pneumonia, not treatment related), and none occurred in the docetaxel arm. Conclusion Noninferiority in overall survival between gefitinib and docetaxel was not demonstrated according to predefined criteria; however, there was no statistically significant difference in overall survival. Secondary end points showed similar or superior efficacy for gefitinib compared with docetaxel. Gefitinib remains an effective treatment option for previously treated Japanese patients with NSCLC.
Gefitinib Versus Vinorelbine in Chemotherapy-Naïve Elderly Patients With Advanced Non–Small-Cell Lung Cancer (INVITE): A Randomized, Phase II Study
Authors: Crinò Lucio , Cappuzzo Federico , Zatloukal Petr , Reck Martin , Pesek Milos , Thompson Joyce C. , Ford Hugo E.R. , Hirsch Fred R. , Varella-Garcia Marileila , Ghiorghiu Serban , Duffield Emma L. , Armour Alison A. , Speake Georgina , Cullen Michael 
Published: September 2008

Purpose This phase II, open-label, parallel-group study compared gefitinib with vinorelbine in chemotherapy-naïve elderly patients with advanced non–small-cell lung cancer (NSCLC). Methods Chemotherapy-naïve patients (age ≥ 70 years) were randomly assigned to gefitinib (250 mg/d orally) or vinorelbine (30 mg/m2 infusion on days 1 and 8 of a 21-day cycle). The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), quality of life (QOL), pulmonary symptom improvement (PSI), and tolerability. Exploratory end points included epidermal growth factor receptor (EGFR) gene copy number by fluorescent in situ hybridization (FISH). Results Patients were randomly assigned to gefitinib (n = 97) or to vinorelbine (n = 99). Hazard ratios (HR; gefitinib v vinorelbine) were 1.19 (95% CI, 0.85 to 1.65) for PFS and 0.98 (95% CI, 0.66 to 1.47) for OS. ORR and disease control rates were 3.1% (95% CI, 0.6 to 8.8) and 43.3% (for gefitinib) and 5.1% (95% CI, 1.7 to 11.4) and 53.5% (for vinorelbine), respectively. Overall QOL improvement and PSI rates were 24.3% and 36.6% (for gefitinib) and 10.9% and 31.0% (for vinorelbine), respectively. In the 54 patients who were EGFR FISH-positive, HRs were 3.13 (95% CI, 1.45 to 6.76) for PFS and 2.88 (95% CI, 1.21 to 6.83) for OS. There were fewer treatment-related grade 3 to 5 adverse events with gefitinib (12.8%) than with vinorelbine (41.7%). Conclusion There was no statistical difference between gefitinib and vinorelbine in efficacy in chemotherapy-naïve, unselected elderly patients with advanced NSCLC, but there was better tolerability with gefitinib. Individuals who were EGFR FISH-positive benefited more from vinorelbine than from gefitinib; this unexpected finding requires further study.
Sinusoidal Obstructive Syndrome Diagnosed With Superparamagnetic Iron Oxide–Enhanced Magnetic Resonance Imaging in Patients With Chemotherapy-Treated Colorectal Liver Metastases
Authors: Ward Janice , Guthrie James A. , Sheridan Maria B. , Boyes Sheila , Smith Jonathan T. , Wilson Daniel , Wyatt Judy I. , Treanor Darren , Robinson Philip J. 
Published: September 2008

Purpose To assess the predictive value of superparamagnetic iron oxide (SPIO) –enhanced T2-weighted gradient echo (GRE) imaging to determine the presence and severity of sinusoidal obstructive syndrome (SOS). Patients and Methods Sixty hepatic resection patients with colorectal metastases treated with chemotherapy underwent unenhanced magnetic resonance imaging (MRI) followed by T2-weighted GRE sequences obtained after SPIO. The images were reviewed in consensus by two experienced observers who determined the presence and severity of linear and reticular hyperintensities, indicating SOS-type liver injury, using a 4-point ordinal scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% CIs for the detection of SOS were calculated. Results Twenty-four of 60 patients had moderate to severe SOS on MRI. MRI achieved a sensitivity of 87% (95% CI, 66% to 97%), specificity of 89% (95% CI, 75% to 97%), PPV of 83% (95% CI, 63% to 95%), and NPV of 92% (95% CI, 77% to 98%). SOS was never found at surgery or histology in patients whose background liver parenchyma was normal on SPIO-enhanced MRI. Conclusion SOS is present in a significant proportion of patients with treated colorectal metastases and is effectively detected on SPIO-enhanced T2-weighted GRE images.
Screening for Small-Cell Lung Cancer: A Follow-Up Study of Patients With Lambert-Eaton Myasthenic Syndrome
Authors: Titulaer Maarten J. , Wirtz Paul W. , Willems Luuk N.A. , van Kralingen Klaas W. , Smitt Peter A.E. Sillevis , Verschuuren Jan J.G.M. 
Published: September 2008

Purpose A small-cell lung carcinoma (SCLC) is found in 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment. Patients and Methods A large nationwide cohort study of consecutive patients in the Netherlands, seen between 1990 and 2007, were screened for the presence of a tumor using chest x-ray, computed tomography of the thorax (CT-thorax), [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), bronchoscopy, and/or mediastinoscopy. Results SCLC was found in 54 patients, and in 46 patients, no tumor was found during a median follow-up of 8 years (range, 3 to 26 years). All patients with SCLC had a positive smoking history and 86% were still smoking at diagnosis. SCLC was found in 92% of these patients within 3 months and in 96% within a year. At first screening, CT-thorax detected an SCLC in 45 patients (83%), whereas chest x-ray found the tumor in only 23 patients (51%). An SCLC was found during secondary screening in another nine patients (median, 3 months; range, 1 to 41 months). In six patients, a lung tumor was found by CT-thorax or FDG-PET, and in three patients, extrapulmonary metastases were found, initially without identifiable tumor mass on CT-thorax. Conclusion In almost all patients (96%), the SCLC was found within 1 year of diagnosis. CT-thorax scans detected most of the tumors (93%) and was far more sensitive than chest x-ray (51%). FDG-PET may have additive value in selected cases. We propose a screening protocol based on CT-thorax and FDG-PET.
An Isolable Boryl-substituted Disilene from the Reaction of an sp2-type Silyl Anion with Haloboranes: Synthesis and Characterization
Authors: Inoue Shigeyoshi , Ichinohe Masaaki , Sekiguchi Akira 
Published: September 2008

Abstract
The disilenyllithium, (t-Bu2MeSi)2Si=Si(SiMet-Bu2)Li (2a), reacted with B-chloropinacolborane (pin)BCl, or B-chlorocatecholborane (cat)BCl in toluene to produce the corresponding boryl-substituted disilenes 3a and 3b, which were isolated as air-sensitive yellow crystals. X-ray crystallographic analysis of 3b showed a nearly planar geometry around the Si=Si bond lacking π-conjugation between the Si=Si bond and a vacant p orbital of boron.
Stress and First Responders: The Need for a Multidimensional Approach to Stress Management
Authors: Reynolds Christine A. , Wagner Shannon L. 
Published: September 2008

AbstractFirst responders are exposed to traumatic, nontraumatic and organisational stressors that conspire to create stress, potentially leading to emotional issues and/or physical or psychological illness. In addition to individual consequences, stress also takes a toll on the function of emergency departments and their communities. Fortunately, police, fire and ambulance agencies have initiated various preventive measures in an effort to mitigate the ill-effects of continued exposure to stressors by their personnel. However, combating stress effectively requires more than offering individual coping skills and access to counseling for first responders. To best preserve the wellbeing of their workers, emergency service administrators must recognise the impact of stress from a variety of sources, including organisational factors, and approach stress prevention in a multi-staged and comprehensive manner, paying special attention to primary stage interventions. When agencies embrace and act on a broad, holistic view of stress management that includes instituting cultural and organisational changes to support stress prevention, significant improvements in the stress level and health of first responders will be possible.
Psychological Consequences of Work Injury: Personality, Trauma and Psychological Distress Symptoms of Noninjured Workers and Injured Workers Returning To, or Remaining at Work
Authors: Wall Cindy L. , Ogloff James R.P. , Morrissey Shirley A. 
Published: September 2008

AbstractDespite growing recognition of the importance of psychosocial factors in reducing ongoing work disability, research into the psychological consequences for injured workers who remain at, or return to work is limited. This study compares injured workers who have returned to, or remained at, work with noninjured workers on measures of personality, trauma symptoms, and symptoms of psychological distress. Data from structured clinical interviews, psychological and self-report questionnaires were gathered from 29 workers, 14 of whom were recovering from an injury at the time of participation. Injured workers demonstrated higher levels of Neuroticism and lower Extraversion, indicating greater emotional instability and lower capacity for adaptively coping with stress when compared to noninjured workers. They also reported subclinical elevations on scales of trauma symptoms, and greater levels of depressive symptoms, somatic complaints, anxiety and sleep disturbance in comparison with noninjured workers. These results suggest that the psychological consequences for workers who return to, or remain at, work following injury may reduce adaptation and increase vulnerability to secondary work disability.
Evaluation of uncertainties in measurements by Monte Carlo simulations with an application for laserscanning
Authors: Koch Karl-Rudolf 
Published: September 2008

Abstract
The trapezoidal and triangular distribution recommended by the “Guide to the Expression of Uncertainty in Measurement (GUM)” are derived to obtain methods for drawing random samples from them. It is demonstrated that variances, covariances and confidence intervals of these distributions can be estimated by the random variates. This method is also applicable for the convolution of different types of distributions like the triangular and the normal distribution. Monte Carlo simulations give in addition estimates of the expected values, variances, covariances and confidence regions of unknown parameters derived from the measurements. Furthermore, hypotheses for the parameters can be tested. This method is applied for the determination of the surface of a motorway by laserscanning. The variances of a laserscanner are specified which are sufficiently small to decide whether detected deformations of the surface are permissible or not.
Microbiological monitoring and automated event sampling at karst springs using LEO-satellites
Authors: Stadler H. , Skritek P. , Sommer R. , Mach R. L. , Zerobin W. , Farnleitner A. H. 
Published: September 2008

Data communication via Low-Earth-Orbit (LEO) Satellites between portable hydrometeorological measuring stations is the backbone of our system. This networking allows automated event sampling with short time increments also for E. coli field analysis. All activities of the course of the event-sampling can be observed on an internet platform based on a Linux-Server. Conventionally taken samples compared with the auto-sampling procedure revealed corresponding results and were in agreement with the ISO 9308-1 reference method. E. coli concentrations were individually corrected by event specific inactivation coefficients (0.10-0.14 day−1), compensating losses due to sample storage at spring temperature in the auto sampler.
Two large summer events in 2005/2006 at an important alpine karst spring (LKAS2) were monitored including detailed analysis of E. coli dynamics (n=271) together with comprehensive hydrological characterisations. High-resolution time series demonstrated a sudden increase of E. coli concentrations in spring water (approximately 2 log10 units) with a specific time delay after the beginning of the event. Statistical analysis suggested the spectral absorption coefficient measured at 254 nm (SAC254) as an early warning surrogate for real time monitoring of faecal input. Together with the LEO-satellite based system it is a helpful tool for early-warning systems in the field of drinking water protection.