bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cancer and Leukemia Group B Cancer in the Elderly Committee: Addressing a Major Cancer Need
Authors: Cohen Harvey Jay , Muss Hyman B. 
Published: June 2006

Abstract
Cancer is a disease of aging, and the majority of cancers occur in persons over 65 years of age. In spite of this, few elders have been represented in clinical trials, and the need for information regarding the treatment of elders with cancer remains great. Recognizing these needs, the Cancer and Leukemia Group B (CALGB) formed an elderly Working Group in 1995, and after initial success in developing clinical studies focused on elders, a Cancer in the Elderly Committee. The Committee's objective is to focus attention on issues specifically relevant to the treatment of cancer in the older patient. Two strategies were developed to achieve this objective: (a) to initiate projects and protocols within the Committee and (b) to foster the initiation of studies by other CALGB committees. The research themes of the Committee and the main thrust of committee's research activities are (a) understanding and overcoming barriers to clinical trials participation; (b) treatment efficacy and pharmacokinetic/pharmacologic issues related to chemotherapy and hormone therapy in the older cancer patient; and (c) improving the quality of life for older cancer patients. The Cancer in the Elderly Committee has been successful in developing, implementing, and completing trials in all these areas and serves as a major resource for clinical trials development for the CALGB.
Radiation Oncology Research in the Cancer and Leukemia Group B
Authors: Bogart Jeffrey A. , Seagren Stephen L. , Glicksman Arvin 
Published: June 2006

Abstract
Radiation oncology initiatives have been an integral component in the evolution of multidisciplinary research in the Cancer and Leukemia Group B. Although early studies in the Group primarily focused on chemotherapy for hematologic and pediatric malignancies, the Radiation Oncology Committee was established in 1972, reflecting the broadening scope of clinical investigation with an increased emphasis on solid tumor research. A major early contribution of the Radiation Oncology Committee was the recognition of the importance of formalized radiation quality review, which led to the development of the Quality Assurance Review Center. The committee has been instrumental in designing trials, in conjunction with our medical oncology and surgical oncology colleagues, to assess multimodality therapy. The results of many of these studies have had important implications for clinical practice. Recent efforts have explored our major research theme of treatment intensification via radiotherapy dose modulation and novel combinations of radiotherapy with sensitizing agents, with an emphasis on safely implementing advanced technologies in the cooperative group setting.
Cancer and Leukemia Group B Clinical Research Associates Committee
Authors: Price Kandie C. , Barrett Barbara K. , Roark Jean M. 
Published: June 2006

Abstract
The Cancer and Leukemia Group B is dedicated to developing and implementing training programs that will enhance the skills and abilities of Clinical Research Associates (CRA) involved in all aspects of data collection and research. Training programs not only improve overall knowledge and professionalism but also improve the integrity of study data. The CRA roles and responsibilities include the following: collect, analyze, and monitor data; collaborate with other members of the health care team; insure regulatory mandates are followed; manage the care of research participants; assist in the recruitment and enrollment of human subjects; protect subjects rights by adhering to Institutional Review Board guidelines, the Code of Federal Regulations; prepare and submit timely adverse event experience reports; maintain case report forms and drug accountability records; educate other health care professionals, patients, and families regarding clinical trials; participate in research audits; and function as a team member with the research team. In addition, CRAs may also be responsible for writing reports, grant, and budget development and the development of protocols, forms, and informed consent documents.
Cancer and Leukemia Group B Breast Committee: Decades of Progress and Plans for the Future
Authors: Hudis Clifford A. , Winer Eric P. 
Published: June 2006

Abstract
The Breast Committee of the Cancer and Leukemia Group B was formed in 1969 under the direction of James Holland. Initial studies examined combination chemotherapy for advanced disease. Although the committee has continued to conduct studies in patients with advanced disease, adjuvant therapy has been an even more important focus for the past 30 years. Over the past 20 years, studies have focused on optimization of chemotherapy through the testing of dose and schedule, the value of adding novel agents, and the role of biological agents. Current and future projects are aimed at exploiting and increasing our growing knowledge of the molecular biology of breast cancer by developing targeted therapies.
Evaluation of a multiplex PCR for bacterial pathogens applied to bronchoalveolar lavage
Authors: Strålin K. , Korsgaard J. , Olcén P. 
Published: June 2006

The present study assessed the diagnostic usefulness of a multiplex PCR (mPCR) forStreptococcus pneumoniae,Haemophilus influenzae,Mycoplasma pneumoniaeandChlamydophila pneumoniaeapplied to bronchoalveolar lavage (BAL).Fibreoptic bronchoscopy was performed on 156 hospitalised adult patients with lower respiratory tract infection (LRTI) and 36 controls. BAL fluid was analysed with bacterial culture and mPCR.By conventional diagnostic methods,S. pneumoniae,H. influenzae,M. pneumoniaeandC. pneumoniaewere aetiological agents in 14, 21, 3.2 and 0% of the LRTI patients, respectively. These pathogens were identified by BAL mPCR in 28, 47, 3.2 and 0.6% of cases, respectively, yielding sensitivities of 86% forS. pneumoniae, 88% forH. influenzae, 100% forM. pneumoniaeand 0% forC. pneumoniae, and specificities of 81, 64, 100 and 99% forS. pneumoniae,H. influenzae,M. pneumoniaeandC. pneumoniae, respectively. Of the 103 patients who had taken antibiotics prior to bronchoscopy,S. pneumoniaewas identified by culture in 2.9% and by mPCR in 31%. Among the controls, mPCR identifiedS. pneumoniaein 11% andH. influenzaein 39%.In lower respiratory tract infection patients, bronchoalveolar lavage multiplex PCR can be useful for identification ofStreptococcus pneumoniae,Mycoplasma pneumoniaeandChlamydophila pneumoniae. The method appears to be particularly useful in patients treated with antibiotics.
Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia
Authors: Spindler C. , Örtqvist Å. 
Published: June 2006

The aim of this study was to evaluate the accuracy of three score systems: the pneumonia severity index (PSI); CURB-65 (confusion; urea >7 mM; respiratory rate ≥30 breaths·min-1; blood pressure <90 mmHg systolic or ≤60 mmHg diastolic; aged ≥65 yrs old); and modified American Thoracic Society rule for predicting intensive care unit (ICU) need and mortality due to bacteraemic pneumococcal pneumonia.All adult patients (n = 114) with invasive pneumococcal pneumonia at the Karolinska University Hospital, Sweden, 1999–2000, were included in the study. Severity scores were calculated and the independent prognostic importance of different variables was analysed by multiple regression analyses.PSI ≥IV, CURB-65 ≥2, and the presence of one major or more than one minor risk factor in mATS all had a high sensitivity, but somewhat lower specificity for predicting death and ICU need. The death rate was 12% (13 out of 114). Severity score and treatment in departments other than the Dept of Infectious Diseases were the only factors independently correlated to death. Patients treated in other departments more often had severe underlying illnesses and were more severely ill on admission. However, a significant difference in death rates remained after adjustment for severity between the two groups.In conclusion, all score systems were useful for predicting the need for intensive care unit treatment and death due to bacteremic pneumococcal pneumonia. The pneumonia severity index was the most sensitive, but CURB-65 was easier to use.
AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis
Authors: Boyle Thomas J , Bao Zhirong , Murray John I , Araya Carlos L , Waterston Robert H 
Published: June 2006

Abstract

Background
The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point.

Results
We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data.

Conclusion
By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development.
Duration of hospital participation in a nationwide stroke registry is associated with improved quality of care
Authors: Hills Nancy K , Johnston S Claiborne 
Published: June 2006

Abstract

Background
There are several proven therapies for patients with ischemic stroke or transient ischemic attack (TIA), including prophylaxis of deep venous thrombosis (DVT) and initiation of antithrombotic medications within 48 h and at discharge. Stroke registries have been promoted as a means of increasing use of such interventions, which are currently underutilized.

Methods
From 1999 through 2003, 86 U.S. hospitals participated in Ethos, a voluntary web-based acute stroke treatment registry. Detailed data were collected on all patients admitted with a diagnosis of TIA or ischemic stroke. Rates of optimal treatment (defined as either receipt or a valid contraindication) were examined within each hospital as a function of its length of time in registry. Generalized estimating equations were used to adjust for patient and hospital characteristics.

Results
A total of 16,301 patients were discharged with a diagnosis of stroke or TIA from 50 hospitals that participated for more than 1 year. Rates of optimal treatment during the first 3 months of participation were as follows: 92.5% for antithrombotic medication within 48 h, 84.6% for antithrombotic medications at discharge, and 77.1% for DVT prophylaxis. Rates for all treatments improved with duration of participation in the registry (p < 0.05), with the most dramatic improvements in the first year.

Conclusion
In a large cohort of patients with stroke or TIA, three targeted quality-improvement measures improved among hospitals participating in a disease-specific registry. Although the changes could be attributed to interventions other than the registry, these findings demonstrate the potential for hospital-level interventions to improve care for patients with stroke and TIA.
VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor
Authors: Berger Ingrid , Stahl Sonja , Rychkova Natalia , Felbor Ute 
Published: June 2006

AbstractVascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF.
The subplacenta of the red-rumped agouti (Dasyprocta leporina L)
Authors: Rodrigues Rosangela Felipe , Carter Anthony M , Ambrosio Carlos Eduardo , dos Santos Tatiana Carlesso , Miglino Maria Angelica 
Published: June 2006

AbstractBackgroundHystricognath rodents have a lobed placenta, comprising labyrinthine exchange areas and interlobular trophoblast. These correspond to the labyrinthine and spongy zones of other rodent placentae. Beneath them, however, is a structure unique to hystricognath rodents called the subplacenta. We here describe the subplacenta of the red-rumped agouti and examine the possible functional correlates of this structure.MethodsPlacentae were collected from early in midgestation to near term of pregnancy and examined by standard histological techniques, immunohistochemistry and transmission electron microscopy. In addition, to study the microvasculature of the subplacenta, vessel casts were inspected by scanning electron microscopyResultsIn the subplacenta, lamellae of connective tissue support a layer of mononuclear cytotrophoblast cells. Beneath this is found syncytiotrophoblast. Clusters of multinuclear giant cells occur in the transition zone between the subplacenta and decidua. There are prominent intercellular spaces between the cytotrophoblast cells. The basal membrane of these cells is often close to fetal blood vessels. The syncytiotrophoblast surrounds an extensive system of lacunae. Microvilli project into these lacunae from the plasma membrane of the syncytiotrophoblast. The syncytial cytoplasm contains electron-dense granules. This is probably the amylase-resistant PAS-positive material identified by histochemistry. The subplacenta is supplied entirely from the fetal circulation. Within it the vessels pursue a tortuous course with sinusoidal dilatations and constrictions.ConclusionThe functions that have been attributed to the subplacenta include hormone production. Our findings are consistent with this interpretation, but suggest that hormone secretion is directed towards the fetal circulation rather than the maternal tissues.
Not enough there, too many here: understanding geographical imbalances in the distribution of the health workforce
Authors: Dussault Gilles , Franceschini Maria Cristina 
Published: May 2006

Abstract
Access to good-quality health services is crucial for the improvement of many health outcomes, such as those targeted by the Millennium Development Goals (MDGs) adopted by the international community in 2000. The health-related MDGs cannot be achieved if vulnerable populations do not have access to skilled personnel and to other necessary inputs. This paper focuses on the geographical dimension of access and on one of its critical determinants: the availability of qualified personnel. The objective of this paper is to offer a better understanding of the determinants of geographical imbalances in the distribution of health personnel, and to identify and assess the strategies developed to correct them. It reviews the recent literature on determinants, barriers and the effects of strategies that attempted to correct geographical imbalances, with a focus on empirical studies from developing and developed countries. An analysis of determinants of success and failures of strategies implemented, and a summary of lessons learnt, is included.
Generation of a single pulmonary pressure-volume curve does not durably affect oxygenation in patients with acute respiratory distress syndrome
Authors: Roch Antoine , Forel Jean-Marie , Demory Didier , Arnal Jean-Michel , Donati Stéphane , Gainnier Marc , Papazian Laurent 
Published: June 2006

Abstract
Introduction
It is possible that taking a static pressure-volume (PV) measurement could durably affect oxygenation and thus interfere with early evaluation of a therapeutic intervention delivered just after that measurement. The aim of the present study was to investigate the effects over time of a single static PV measurement on gas exchange and haemodynamics; the PV measurements were taken using a super syringe and by using the constant flow method in patients with acute respiratory distress syndrome.

Method
We conducted a prospective, randomized and controlled interventional study in an intensive care unit. The study was conducted in 17 patients with early acute respiratory distress syndrome ventilated with a tidal volume of 6.9 ± 1.0 ml/kg, a plateau pressure of 27 ± 7 cmH2O and a positive end-expiratory pressure [PEEP] of 10 cmH2O. They were all evaluated for 1 hour after each of the following two measurements was taken and during a control period (in a randomized order): generation of a PV curve using a 2 l super syringe (PVSS; insufflated volume = 1824 ± 381 ml, plateau pressure = 46 ± 9 cmH2O); and generation of a PV curve using the constant flow method on the ventilator (PVCF; insufflated volume = 1120 ± 115 ml in zero end-expiratory pressure after 20 s expiratory pause, plateau pressure = 46 ± 11 cmH2O). The maximal airway pressure allowed during PV measurement was 60 cmH2O. PEEP was set to 10 cmH2O immediately after PV measurement. Partial arterial oxygen tension (Pao2), partial carbon dioxide tension (Paco2) and mean arterial pressure were recorded each minute.

Results
PV measurement did not significantly affect Pao2, Paco2, mean arterial pressure and lung mechanics. Two patients exhibited a sustained increase in Pao2 by more than 20% after PVCF (>60 minutes). Two patients exhibited a decrease in Pao2 by more than 20% after PVSS, which was sustained in one. These latter patients had an upper inflection point identified on the PV curve. After PVSS, Paco2 increased by more than 10 mmHg in two patients and returned to baseline values after 15 minutes. One patient exhibited a decrease in mean arterial pressure by more than 10 mmHg for less than 5 minutes after PVSS and one patient after PVCF.

Conclusion
Evaluation of the effects of a strategy aimed at improving oxygenation can be reliably recorded early after a single PV measurement that is not followed by a change in PEEP level. PV measurement using the constant flow method improves oxygenation in a limited number of patients.
Cognitive stimulation therapy for people with dementia: cost-effectiveness analysis
Authors: Knapp Martin , Thorgrimsen Lene , Patel Anita , Spector Aimee , Hallam Angela , Woods Bob , Orrell Martin 
Published: June 2006

BackgroundPsychological therapy groups for people with dementia are widely used, but their cost-effectiveness has not been explored.AimsTo investigate the cost-effectiveness of an evidence-based cognitive stimulation therapy (CST) programme for people with dementia as part of a randomised controlled trial.MethodA total of 91 people with dementia, living in care homes or the community, received a CST group intervention twice weekly for 8 weeks; 70 participants with dementia received treatment as usual. Service use was recorded 8 weeks before and during the 8-week intervention and costs were calculated. A cost-effectiveness analysis was conducted with cognition as the primary outcome, and quality of life as the secondary outcome. Cost-effectiveness acceptability curves were plotted.ResultsCognitive stimulation therapy has benefits for cognition and quality of life in dementia, and costs were not different between the groups. Under reasonable assumptions, there is a high probability that CST is more cost-effective than treatment as usual, with regard to both outcome measures.ConclusionsCognitive stimulation therapy for people with dementia has effectiveness advantages over, and may be more cost-effective than, treatment as usual.
Family Life and Relationships in the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA)
Authors: MacGregor Caitriona Aine , Sheerin Declan 
Published: June 2006

Aims and MethodThe Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) were developed as a routine measure of outcomes in child and adolescent psychiatry. In a preliminary study we administered sub-scale 12 of HoNOSCA (Family Life and Relationships) to 20 families and compared the results with two well-established measures of family functioning and a measure of abnormal psychosocial situations associated with psychopathology.ResultsStrong correlations were found between HoNOSCA sub-scale 12 and both self-assessed and clinician-assessed measures of family functioning. However, there was little relationship between HoNOSCA (12) and a measure of abnormal psychosocial situations.Clinical ImplicationsHoNOSCA (12) appears to provide a quick and valid assessment of overall family dysfunction and can be used in a time-efficient manner as a means to assess where further more comprehensive family assessment or family therapy may be required.
Conformation and stability of the Streptococcus pyogenes pSM19035-encoded site-specific β recombinase, and identification of a folding intermediate
Authors: Bhardwaj Anshul , Welfle Karin , Misselwitz Rolf , Ayora Silvia , Alonso Juan C. , Welfle Heinz 
Published: June 2006

Abstract
Solution properties of β recombinase were studied by circular dichroism and fluorescence spectroscopy, size exclusion chromatography, analytical ultracentrifugation, denaturant-induced unfolding and thermal unfolding experiments. In high ionic strength buffer (1 M NaCl) β recombinase forms mainly dimers, and strongly tends to aggregate at ionic strength lower than 0.3 M NaCl. Urea and guanidinium chloride denaturants unfold β recombinase in a two-step process. The unfolding curves have bends at approximately 5 M and 2.2 M in urea and guanidinium chloride-containing buffers. Assuming a three-state unfolding model (N2→2I→2U), the total free energy change from 1 mol of native dimers to 2 mol of unfolded monomers amounts to ΔG
tot=17.9 kcal/mol, with ΔG
N2→2I=4.2 kcal/mol for the first transition and ΔG
I→U=6.9 kcal/mol for the second transition. Using sedimentation-equilibrium analytical ultracentrifugation, the presence of β recombinase monomers was indicated at 5 M urea, and the urea dependence of the circular dichroism at 222 nm strongly suggests that folded monomers represent the unfolding intermediate.
Pathogenicity of catalytic antibodies: catalytic activity of Bence Jones proteins from myeloma patients with renal impairment can elicit cytotoxic effects
Authors: Matsuura Kinji , Ohara Kyoko , Munakata Hiroshi , Hifumi Emi , Uda Taizo 
Published: June 2006

AbstractSome Bence Jones proteins (BJPs) can display catalytic activity. Although the catalytic activity of BJPs might be associated with the pathogenesis of disease, this relationship has not yet been established. We tested the effects of seven BJPs on LLC-PK1 cells to assess their pathogenicity. Two out of the seven BJPs showed cytotoxic activity, as assessed by microscopic analysis, the WST method and TUNEL staining. Moreover, the cytotoxic BJPs were excreted by patients who presented with renal impairment. The cytotoxic BJPs displayed 20- to 40-fold higher catalytic activities (kcatof 3.5–2.2 min-1) in hydrolyzing a chromogenic substrate compared to the other BJPs. By treating the cytotoxic BJPs with diisopropylfluorophosphate, they lost not only their catalytic activity, but also the cytotoxic effects. These results indicate a direct link between cytotoxicity and the catalytic activity of the BJPs. The catalytic activity of BJPs contributes to the pathogenesis, as well as to development, of symptoms of multiple myeloma. Inhibition of the catalytic activity of BJPs may form the basis of a novel treatment for multiple myeloma patients with renal dysfunction.