tbuckley/cabot-search huggingface dataset:
Half of disability assessment bodies will be from the NHS
Authors: A. O'Dowd
Journal: BMJ (2013)

Half of the 14 partner bodies that have been subcontracted to carry out new disability assessment work led by a private company are NHS organisations.

Atos Healthcare, the company which the government contracted to do assessments for a new disability benefit, published a list this week of the 14 “supply chain partners” that it has made agreements with to do most of the frontline work.

Observers, however, are puzzled as to why public sector providers have gone through a private sector intermediary to do work for the public sector.

Last year, the Department for Work and Pensions awarded a five year contract to Atos, worth £400m (€464m; $620m), to deliver assessments for a new disability benefit …
Subsidy of social functions by drug companies.
Authors: D Hilton
Journal: BMJ (1979)

ment.We do not agree.Surely it is better to recognise the importance of obstetric anaes- thetic services and improve the services where they are inadequate.Currently the recruitment of doctors into anaesthesia is excellent and the opportunity exists.Unfortunately, medical administrators seeking to save money might misuse the views of Professor Hibbard and his colleagues and block the improvements that are necessary.This is the true importance of the argument.
International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema
Authors: E. von Mutius
Journal: Thorax (2000)

<h3>BACKGROUND</h3> An ecological analysis was conducted of the relationship between tuberculosis notification rates and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in 85 centres from 23 countries in which standardised data are available. These essentially comprised countries in Europe as well as the USA, Canada, Australia, and New Zealand. <h3>METHODS</h3> Tuberculosis notification rates were obtained from the World Health Organization. Data on the prevalence of symptoms of asthma, rhinitis, and eczema in 235 477 children aged 13–14 years were based on the responses to the written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product (GNP) as an estimate of the level of affluence. <h3>RESULTS</h3> Tuberculosis notification rates were significantly inversely associated with the lifetime prevalence of wheeze and asthma and the 12 month period prevalence of wheeze at rest as assessed by the video questionnaire. An increase in the tuberculosis notification rates of 25 per 100 000 was associated with an absolute decrease in the prevalence of wheeze ever of 4.7%. Symptoms of allergic rhinoconjunctivitis in the past 12 months were inversely associated with tuberculosis notification rates, but there were no other significant associations with other ISAAC questions on allergic rhinoconjunctivitis or atopic eczema. <h3>CONCLUSIONS</h3> These findings are consistent with recent experimental evidence which suggests that exposure to <i>Mycobacterium tuberculosis</i> may reduce the risk of developing asthma.
An In Vivo MRI Study of Prefrontal Cortical Complexity in First-Episode Psychosis
Authors: Laura C. Wiegand, Simon K. Warfield, James J. Levitt, Yoshio Hirayasu, Dean F. Salisbury, Stephan Heckers, Sylvain Bouix, Daniel Schwartz, Magdalena Spencer, Chandlee C. Dickey, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley, Martha E. Shenton
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The purpose of this study was to investigate abnormalities in the surface complexity of the prefrontal cortex and in the hemispheric asymmetry of cortical complexity in first-episode patients with schizophrenia. METHOD: An estimate of the surface complexity of the prefrontal cortex was derived from the number of voxels along the boundary between gray matter and CSF. Magnetic resonance imaging scans were acquired from patients with a first episode of schizophrenia (N=17), patients with a first episode of affective psychosis (N=17), and normal comparison subjects (N=17), age-matched within a narrow age range (18–29 years). This study group was the focus of a previous study that showed lower prefrontal cortical volume in patients with schizophrenia. RESULTS: Prefrontal cortical complexity was not significantly different among the groups. However, the schizophrenia patients differed significantly from the normal comparison subjects in asymmetry, with the schizophrenia patients showing less left-greater-than-right asymmetry in cortical complexity than the comparison subjects. CONCLUSIONS: An abnormal pattern of asymmetry in the prefrontal cortex of first-episode patients with schizophrenia provides evidence for a neurodevelopmental mechanism in the etiology of schizophrenia.
Identification of a 24-Gene Prognostic Signature That Improves the European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: An International Collaborative Study
Authors: Zejuan Li, Tobias Herold, Chunjiang He, Peter J.M. Valk, Ping Chen, Vindi Jurinovic, Ulrich Mansmann, Michael D. Radmacher, Kati S. Maharry, Miao Sun, Xinan Yang, Hao Huang, Xi Jiang, Maria-Cristina Sauerland, Thomas Büchner, Wolfgang Hiddemann, Abdel Elkahloun, Mary Beth Neilly, Yanming Zhang, Richard A. Larson, Michelle M. Le Beau, Michael A. Caligiuri, Konstanze Döhner, Lars Bullinger, Paul P. Liu, Ruud Delwel, Guido Marcucci, Bob Lowenberg, Clara D. Bloomfield, Janet D. Rowley, Stefan K. Bohlander, Jianjun Chen
Journal: Journal of Clinical Oncology (2013)

To identify a robust prognostic gene expression signature as an independent predictor of survival of patients with acute myeloid leukemia (AML) and use it to improve established risk classification.Four independent sets totaling 499 patients with AML carrying various cytogenetic and molecular abnormalities were used as training sets. Two independent patient sets composed of 825 patients were used as validation sets. Notably, patients from different sets were treated with different protocols, and their gene expression profiles were derived using different microarray platforms. Cox regression and Kaplan-Meier methods were used for survival analyses.A prognostic signature composed of 24 genes was derived from a meta-analysis of Cox regression values of each gene across the four training sets. In multivariable models, a higher sum value of the 24-gene signature was an independent predictor of shorter overall (OS) and event-free survival (EFS) in both training and validation sets (P < .01). Moreover, this signature could substantially improve the European LeukemiaNet (ELN) risk classification of AML, and patients in three new risk groups classified by the integrated risk classification showed significantly (P < .001) distinct OS and EFS.Despite different treatment protocols applied to patients and use of different microarray platforms for expression profiling, a common prognostic gene signature was identified as an independent predictor of survival of patients with AML. The integrated risk classification incorporating this gene signature provides a better framework for risk stratification and outcome prediction than the ELN classification.
677 FREQUENCY AND T-CELL RECEPTOR (TCR) REPERTOIRE OF HEPATITIS C VIRUS (HCV)-SPECIFIC CD8 T-CELLS IN HCV-SERONEGATIVE INDIVIDUALS
Authors: R. Bakshi, V. Schlaphoff, P.V. Suneetha, P. Malinski, M.P. Manns, H. Wedemeyer, M. Cornberg
Journal: Journal of Hepatology (2010)
ASIC2a and ASIC3 Heteromultimerize to Form pH-Sensitive Channels in Mouse Cardiac Dorsal Root Ganglia Neurons
Authors: Tomonori Hattori, Jie Chen, Anne Marie S. Harding, Margaret P. Price, Yongjun Lu, Francois M. Abboud, Christopher J. Benson
Journal: Circulation Research (2009)

Acid-sensing ion channels (ASICs) are Na+ channels that are activated by acidic pH. Their expression in cardiac afferents and remarkable sensitivity to small pH changes has made them leading candidates to sense cardiac ischemia.Four genes encode six different ASIC subunits, however it is not yet clear which of the ASIC subunits contribute to the composition of ASICs in cardiac afferents.Here, we labeled cardiac afferents using a retrograde tracer dye in mice, which allowed for patch-clamp studies of murine cardiac afferents. We found that a higher percentage of cardiac sensory neurons from the dorsal root ganglia respond to acidic pH and generated larger currents compared to those from the nodose ganglia. The ASIC-like current properties of the cardiac dorsal root ganglia neurons from wild-type mice most closely matched the properties of ASIC2a/3 heteromeric channels. This was supported by studies in ASIC-null mice: acid-evoked currents from ASIC3(-/-) cardiac afferents matched the properties of ASIC2a channels, and currents from ASIC2(-/-) cardiac afferents matched the properties of ASIC3 channels.We conclude that ASIC2a and -3 are the major ASIC subunits in cardiac dorsal root ganglia neurons and provide potential molecular targets to attenuate chest pain and deleterious reflexes associated with cardiac disease.
Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis
Authors: B.A.M. Heemskerk-Gerritsen, M.B.E. Menke-Pluijmers, A. Jager, M.M.A. Tilanus-Linthorst, L.B. Koppert, I.M.A. Obdeijn, C.H.M. van Deurzen, J.M. Collée, C. Seynaeve, M.J. Hooning
Journal: Annals of Oncology (2013)
The Impact of Newer Treatment Modalities on Survival in Patients With Hepatocellular Carcinoma
Authors: Naota Taura, Keisuke Hamasaki, Kazuhiko Nakao, Tatsuki Ichikawa, Daisuke Nishimura, Takashi Goto, Mariko Fukuta, Hiroshi Kawashimo, Masumi Fujimoto, Koichiro Kusumoto
Journal: Clinical Gastroenterology and Hepatology (2006)
SOX1 down-regulates β-catenin and reverses malignant phenotype in nasopharyngeal carcinoma
Authors: Zhong Guan, Jialiang Zhang, Jing Wang, Hefei Wang, Feimeng Zheng, Jieren Peng, Yaodong Xu, Min Yan, Bing Liu, Bai Cui, Ying Huang, Quentin Liu
Journal: Molecular Cancer (2014)

Aberrant activation of the Wnt/β-catenin signaling pathway is an important factor in the development of nasopharyngeal carcinoma (NPC). Previous studies have demonstrated that the developmental gene sex-determining region Y (SRY)-box 1 (SOX1) inhibits cervical and liver tumorigenesis by interfering with the Wnt/β-catenin signaling pathway. However, the role of SOX1 in NPC remains unclear. This study investigates the function of SOX1 in NPC pathogenesis. Down-regulation of SOX1 was detected in NPC cell lines and tissues. Besides, quantitative methylation-specific polymerase chain reaction revealed that SOX1 promoter was hypermethylated in NPC cell lines. Ectopic expression of SOX1 in NPC cells suppressed colony formation, proliferation and migration in vitro and impaired tumor growth in nude mice. Restoration of SOX1 expression significantly reduced epithelial-mesenchymal transition, enhanced cell differentiation and induced cellular senescence. Conversely, transient knockdown of SOX1 by siRNA in these cells partially restored cell proliferation and colony formation. Notably, SOX1 was found to physically interact with β-catenin and reduce its expression independent of proteasomal activity, leading to inhibition of Wnt/β-catenin signaling and decreased expression of downstream target genes. SOX1 decreases the expression of β-catenin in a proteasome-independent manner and reverses the malignant phenotype in NPC cells.
Protective Role of CXC Receptor 4/CXC Ligand 12 Unveils the Importance of Neutrophils in Atherosclerosis
Authors: Alma Zernecke, Ilze Bot, Yassin Djalali-Talab, Erdenechimeg Shagdarsuren, Kiril Bidzhekov, Svenja Meiler, Regina Krohn, Andreas Schober, Markus Sperandio, Oliver Soehnlein, Jörg Bornemann, Frank Tacke, Erik A. Biessen, Christian Weber
Journal: Circulation Research (2007)

The CXC ligand (CXCL)12/CXC receptor (CXCR)4 chemokine-receptor axis controls hematopoiesis, organ development, and angiogenesis, but its role in the inflammatory pathogenesis of atherosclerosis is unknown. Here we show that interference with Cxcl12/Cxcr4 by a small-molecule antagonist, genetic Cxcr4 deficiency, or lentiviral transduction with Cxcr4 degrakine in bone marrow chimeras aggravated diet-induced atherosclerosis in apolipoprotein E-deficient (Apoe-/-) or LDL receptor-deficient (Ldlr-/-) mice. Chronic blockade of Cxcr4 caused leukocytosis and an expansion of neutrophils and increased neutrophil content in plaques, associated with apoptosis and a proinflammatory phenotype. Whereas circulating neutrophils were recruited to atherosclerotic lesions, depletion of neutrophils reduced plaque formation and prevented its exacerbation after blocking Cxcr4. Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice.
EP-02 * MOLECULAR CLASSIFICATION OF EPENDYMOMAS IN A JAPANESE COHORT
Authors: K. Fukuoka, S. Fukushima, S. Yamashita, T. Shofuda, T. Nakamura, K. Yamasaki, H. Takami, Y. Matsushita, T. Ushijima, Y. Narita, Y. Kanemura, M. Yamasaki, S. Shibui, H. Arai, R. Nishikawa, K. Ichimura
Journal: Neuro-Oncology (2015)

INTRODUCTION: Based on a series of extensive molecular analysis in the recent years, a scheme of molecular classification for ependymomas has been proposed. The efficacy of the classification however needs to be validated in an independent cohort of different ethnicity. For this purpose, Japan Pediatric Molecular Neuro-Oncology Group (JPMNG) has been established as a joint project of Japan Society of Neuro-Oncology (JSNO) and Japan Society of Pediatric Neurosurgery (JSPN) in order to centrally collect tumor samples and patient information and to provide a standardized molecular classification in pediatric brain tumors. METHODS: We studied genome-wide methylation analysis in ependymomas by using Infinium HumanMethylation450K BeadChip (HM450K). To detect C11orf95-RELA fusions and YAP1 associated fusions, we performed FISH and RT-PCR followed by Sanger sequencing,. Array CGH was used to assess chromothripsis in the cases with RELA or YAP1 fusions. RESULTS: The number of samples collected so far is 96. Among them, 64 samples (fresh frozen 53, FFPE 11) were analyzed with HM450K array. Posterior fossa (PF) ependymomas were subdivided into two groaups. One group, which clusters with reported PFA tumors, included all infantile-onset cases and histopathologically most anaplastic ependymoma (WHO grade3). The other includes most adult cases, ependymoma (WHO grade2) cases, and all primary spinal tumor cases and clustered with the PFB tumors. Supratentorial (ST) ependymomas had generally higher levels of methylation than either PFA or PFB tumors. C11orf95-RELA fusion gene were detected in 7 of 11 ST tumors. There were no C11orf95-YAP1 fusion positive cases examined by RT-PCR. Chromothripsis was detected in 2 out of 6 fusion-positive tumors. CONCLUSIONS: Japanese PF ependymomas were successfully classified into PFA and PFB by methylation profiling. C11orf95-RELA fusions were only observed in ST ependymomas but they may not be always associated with chromothripsis detected by array CGH. The pathogenesis of fusion-negative ST ependymomas needs further investigation.
Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer
Authors: Justin E. Bekelman, Nandita Mitra, Elizabeth A. Handorf, Robert G. Uzzo, Stephen A. Hahn, Daniel Polsky, Katrina Armstrong
Journal: Journal of Clinical Oncology (2015)

Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age &gt; 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P &gt; .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival.
A Randomized Trial of Rosiglitazone Therapy in Patients With Inadequately Controlled Insulin-Treated Type 2 Diabetes
Authors: Philip Raskin, Marc Rendell, Matthew C. Riddle, Jo F. Dole, Martin I. Freed, Julio Rosenstock
Journal: Diabetes Care (2001)

OBJECTIVE—To determine the efficacy and safety of rosiglitazone (RSG) when added to insulin in the treatment of type 2 diabetic patients who are inadequately controlled on insulin monotherapy. RESEARCH DESIGN AND METHODS—After 8 weeks of insulin standardization and placebo (PBO) run-in, 319 type 2 diabetic patients with mean baseline HbA1c ≥7.5% (8.9 ± 1.1 to 9.1 ± 1.3) on twice-daily insulin therapy (total daily dose ≥30 U) were randomized to 26 weeks of additional treatment with RSG (4 or 8 mg daily) or PBO. Insulin dose could be down- titrated only for safety reasons. The primary end point was reduction of HbA1c from baseline. RESULTS—RSG 4 and 8 mg daily significantly improved glycemic control, which was unchanged on PBO. By intent-to-treat analysis, treatment with RSG 8 mg plus insulin resulted in a mean reduction from baseline in HbA1c of 1.2% (P &amp;lt; 0.0001), despite a 12% mean reduction of insulin dosage. Over 50% of subjects treated daily with RSG 8 mg plus insulin had a reduction of HbA1c ≥1.0%. Neither total:HDL cholesterol nor LDL:HDL cholesterol ratios significantly changed with RSG treatment. Serious adverse events did not differ among groups. CONCLUSIONS—The addition of RSG to insulin treatment results in significant improvement in glycemic control and is generally well tolerated.
Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study
Authors: F. Trillsch, S. Mahner, L. Woelber, E. Vettorazzi, A. Reuss, N. Ewald-Riegler, N. de Gregorio, C. Fotopoulou, B. Schmalfeldt, A. Burges, F. Hilpert, T. Fehm, W. Meier, P. Hillemanns, L. Hanker, A. Hasenburg, H.G. Strauss, M. Hellriegel, P. Wimberger, K. Baumann, M.D. Keyver-Paik, U. Canzler, K. Wollschlaeger, D. Forner, J. Pfisterer, W. Schroeder, K. Muenstedt, B. Richter, F. Kommoss, S. Hauptmann, A. du Bois
Journal: Annals of Oncology (2014)
Methodological Development of a Clonogenic Assay to Determine Endothelial Progenitor Cell Potential
Authors: Haruchika Masuda, Cantas Alev, Hiroshi Akimaru, Rie Ito, Tomoko Shizuno, Michiru Kobori, Miki Horii, Toshiya Ishihara, Kazuya Isobe, Mitsuhiro Isozaki, Johbu Itoh, Yoshiko Itoh, Yoshinori Okada, Brendan A.S. McIntyre, Shunichi Kato, Takayuki Asahara
Journal: Circulation Research (2011)

The precise and conceptual insight of circulating endothelial progenitor cell (EPC) kinetics is hampered by the absence of an assay system capable of evaluating the EPC differentiation cascade. An assay system for EPC colony formation was developed to delineate circulating EPC differentiation. EPC colony-forming assay using semisolid medium and single or bulk CD133(+) cells from umbilical cord blood exhibited the formation of two types of attaching cell colonies made of small or large cells featuring endothelial lineage potential and properties, termed small EPC colony-forming units and large EPC colony-forming units, respectively. In vitro and in vivo assays of each EPC colony-forming unit cell revealed a differentiation hierarchy from small EPC to large EPC colonies, indicating a primitive EPC stage with highly proliferative activity and a definitive EPC stage with vasculogenic properties, respectively. Experimental comparison with a conventional EPC culture assay system disclosed EPC colony-forming unit cells differentiate into noncolony-forming early EPC. The fate analysis of single CD133(+) cells into the endothelial and hematopoietic lineage was achieved by combining this assay system with a hematopoietic progenitor assay and demonstrated the development of colony-forming EPC and hematopoietic progenitor cells from a single hematopoietic stem cell. EPC colony-forming assay permits the determination of circulating EPC kinetics from single or bulk cells, based on the evaluation of hierarchical EPC colony formation. This assay further enables a proper exploration of possible links between the origin of EPC and hematopoietic stem cells, representing a novel and powerful tool to investigate the molecular signaling pathways involved in EPC biology.
Lung clearance index: should we really go back to nitrogen washout?
Authors: Jørgen G. Nielsen
Journal: European Respiratory Journal (2014)

A recent editorial in the European Respiratory Journal [1] recognises that the fundamental scientific data on lung clearance index (LCI) obtained by sulfur hexafluoride (SF 6 ) multiple-breath washout (MBW) have paved the way for clinical use of LCI.Although the editorial stresses the need for standardisation, it also appears to suggest that SF 6 can be replaced by nitrogen (N 2 ) as the washout gas.We (Innovision ApS, Odense, Denmark) are the manufacturer of the AMIS 2000 medical mass spectrometer system that, using user-specific software and hardware, was adapted to perform MBW.The AMIS 2000-based devices are now considered the ''gold standard'' device for SF 6 LCI measurements in cystic fibrosis patients by opinion leaders in the field [2].This device has been used in the vast majority of studies demonstrating the clinical value of SF 6 LCI in cystic fibrosis patients, with one recent notable exception: the demonstration of the change in LCI caused by Ivacaftor in cystic fibrosis patients with normal forced expiratory volume in 1 s, where a prototype version of our other system, Innocor, adapted for open-circuit SF 6 LCI, was used [3].