tbuckley/cabot-search huggingface dataset:
P288 A Unified Ranking System For Key COPD Outcome Measures Showing Variation Between PCTs and Hospitals-Helping to Drive Change: Abstract P288 Table 1
Authors: AG Davison, L Jongepier, JR Flowers, K Smith
Journal: Thorax (2012)

<h3></h3> The White Paper “Equity and Excellence. Liberating the NHS” stated that the health service must be focused on outcomes and quality standards that deliver them. INHALE (Interactive Health Atlas for Lung in UK), www.inhale@nhs.uk.contains over 70 outcome measures for all the Regions and PCTs in UK. Demonstrating variation in outcomes drives service change. Hospital mortality has been reduced using this methodology. Wright J, Dugdale B, Hammond I et al Learning from death. A hospital mortality reduction programme. JRSM 2006; 99: 303–308. <h3>Methods</h3> Four key outcome measures which reflect hospital, community and primary care of COPD have been selected from INHALE These are COPD mortality rate per 100,000 PCT population 2008–10, hospital bed-days per 1000 population 2010–11,% hospital readmissions within 28 days for COPD 2010–11, ratio of expected to observed COPD cases over the PCT for 2010–11. An action list of COPD service improvements has been prepared by the EoE Respiratory Team. <h3>Results</h3> There is considerable variation for each outcome measure across the East of England (EoE). 2.04 fold for mortality, 2.61 fold for bed-days, 1.67 fold for hospital readmissions and 1.56 for Observed/Expected. These measurements have been ranked across the PCTs. The ranking of these 4 outcome measures have been summated and then ranked to give an overall PCT ranking. The Table shows ranking of each outcome measure and unified summated ranking. <h3>Conclusion</h3> The wide variation in outcomes across the EoE has been more clearly demonstrated by using a ranking system. An EoE data pack has been produced demonstrating this and includes the overall ranking, bar charts and funnel plots of the outcome measures, a trend analysis of the outcome measures, and the suggested service improvements. This has been circulated to all respiratory consultants, CCG leads, local respiratory networks, and hospital chief executives in the Region. This allows comparisons to be made and helps to drive change. Localities and hospitals have started to draw up service improvements.
Ornithine Decarboxylase G316A Genotype Is Prognostic for Colorectal Adenoma Recurrence and Predicts Efficacy of Aspirin Chemoprevention
Authors: Richard A. Hubner, Kenneth R. Muir, Jo-Fen Liu, Richard F.A. Logan, Matthew J. Grainge, Richard S. Houlston
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The chemopreventive activity of aspirin in colorectal neoplasia may be explained in part by its effect on polyamine metabolism. The ornithine decarboxylase (ODC) G316A polymorphism affects polyamine metabolism through altered expression of ODC. We investigated the influence of ODC G316A on the chemopreventive activity of aspirin in colorectal adenoma (CRA) recurrence. Experimental Design: We genotyped ODC G316A in 546 individuals in the United Kingdom Colorectal Adenoma Prevention trial of aspirin for CRA recurrence prevention and pooled our findings with data from two other randomized intervention trials. Results: The United Kingdom Colorectal Adenoma Prevention participants with homozygous ODC 316AA genotype were at reduced CRA recurrence risk [relative risk (RR), 0.43; 95% confidence interval (95% CI), 0.16-1.15], particularly if also exposed to aspirin (RR, 0.24; 95% CI, 0.03-1.71). In the pooled analysis of 2,207 individuals, those with homozygous ODC 316AA genotype were at significantly reduced CRA recurrence risk (RR, 0.68; 95% CI, 0.47-0.99). Following stratification by genotype and aspirin exposure, individuals with homozygous wild-type or heterozygous genotypes derived modest benefit from aspirin (RR, 0.85; 95% CI, 0.72-1.01), whereas in those with both ODC 316AA genotype and aspirin exposure recurrence risk was halved (RR, 0.52; 95% CI, 0.29-0.91). Conclusion: The ODC G316A genotype is prognostic for CRA recurrence and predictive of an enhanced response to aspirin in preventing recurrence. This variant has the potential to be a clinically useful genetic marker to identify individuals likely to derive the greatest benefit from aspirin chemoprevention.
A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer
Authors: S.B. Kaye, C.J. Poole, A. Dańska-Bidzińska, L. Gianni, G. Del Conte, V. Gorbunova, E. Novikova, A. Strauss, M. Moczko, V.A. McNally, G. Ross, I. Vergote
Journal: Annals of Oncology (2012)
Role of Eph/ephrin tyrosine kinase in malignant glioma
Authors: M. Nakada, Y. Hayashi, J.-i. Hamada
Journal: Neuro-Oncology (2011)

Accumulating evidence has revealed that the tyrosine kinases play a major role in glioma proliferation and invasion. The largest family of tyrosine kinases, the Eph family, and its ligands, the ephrins, are frequently overexpressed in glioma, suggesting important roles for their bidirectional signals in glioma pathobiology. Ephs bind to cell surface–associated ephrin ligands on neighboring cells and have many biological functions during embryonic development of the central nervous system, including axon mapping, cell migration, and angiogenesis. Recent findings suggest that Eph/ephrin signaling affects glioma cell growth, migration, and invasion in vitro and in vivo. However, their roles in glioma seem complex, because both tumor growth promoter and suppressor potentials have been ascribed to Ephs and ephrins. Here, we review recent advances in research on the role of Eph/ephrin signaling in glioma and suggest that the Eph/ephrin system could be a potential target of glioma therapy.
Tumor-Targeted Synergistic Blockade of MAPK and PI3K from a Layer-by-Layer Nanoparticle
Authors: Erik C. Dreaden, Yi Wen Kong, Stephen W. Morton, Santiago Correa, Ki Young Choi, Kevin E. Shopsowitz, Kasper Renggli, Ronny Drapkin, Michael B. Yaffe, Paula T. Hammond
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Cross-talk and feedback between the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cell signaling pathways is critical for tumor initiation, maintenance, and adaptive resistance to targeted therapy in a variety of solid tumors. Combined blockade of these pathways—horizontal blockade—is a promising therapeutic strategy; however, compounded dose-limiting toxicity of free small molecule inhibitor combinations is a significant barrier to its clinical application. Experimental Design: AZD6244 (selumetinib), an allosteric inhibitor of Mek1/2, and PX-866, a covalent inhibitor of PI3K, were co-encapsulated in a tumor-targeting nanoscale drug formulation—layer-by-layer (LbL) nanoparticles. Structure, size, and surface charge of the nanoscale formulations were characterized, in addition to in vitro cell entry, synergistic cell killing, and combined signal blockade. In vivo tumor targeting and therapy was investigated in breast tumor xenograft–bearing NCR nude mice by live animal fluorescence/bioluminescence imaging, Western blotting, serum cytokine analysis, and immunohistochemistry. Results: Combined MAPK and PI3K axis blockade from the nanoscale formulations (160 ± 20 nm, −40 ± 1 mV) was synergistically toxic toward triple-negative breast (MDA-MB-231) and RAS-mutant lung tumor cells (KP7B) in vitro, effects that were further enhanced upon encapsulation. In vivo, systemically administered LbL nanoparticles preferentially targeted subcutaneous MDA-MB-231 tumor xenografts, simultaneously blocked tumor-specific phosphorylation of the terminal kinases Erk and Akt, and elicited significant disease stabilization in the absence of dose-limiting hepatotoxic effects observed from the free drug combination. Mice receiving untargeted, but dual drug–loaded nanoparticles exhibited progressive disease. Conclusions: Tumor-targeting nanoscale drug formulations could provide a more safe and effective means to synergistically block MAPK and PI3K in the clinic. Clin Cancer Res; 21(19); 4410–9. ©2015 AACR.
Number of organ donors rises by 15% in Spain after doctors are given good practice guide
Authors: A. Garcia Rada
Journal: BMJ (2011)

A guide circulated to health professionals in Spain that was based on the results of a three year study of how different hospitals tackle the issue of organ donation from brain stem dead donors seems to have significantly improved donation rates. 

The Spanish National Transplant Organisation (Organizacion Nacional de Transplantes (ONT)) released the new guide to good practice in the last quarter of 2010 and has seen donation rates improve sharply in the first quarter of this year.

The ONT’s three year project, “Benchmarking the Process of Donation,” was part of its strategic plan to raise the national …
Fetal liver and bone marrow JORO 75+ lymphocyte progenitors are precursors of CD4+8- TCR/CD3- early thymocytes.
Authors: E Golunski, R Palacios
Journal: The Journal of Experimental Medicine (1994)

We show here that cell sorter purified JORO 75+ lymphocyte progenitors from fetal liver or bone marrow of adult mice give rise in vitro to CD4+8- T cell receptor (TCR)/CD3- early thymocytes and CD4+8- TCR/CD3+ thymocyte subsets after coculture with the EH6 subcapsular thymic epithelial cell line, recombinant interleukin 7 (rIL-7) and F (supernatants from the FLS4.1 fetal liver stromal cell line). We find that in cultures that had additionally received rIL-2, CD4-8+ TCR/CD3+ cells were also generated. The results strongly suggest that fetal liver and marrow JORO 75+ lymphocyte progenitors are precursors to the early CD4+8- TCR/CD3- intrathymic population previously identified in the adult mouse. The EH6 subcapsular thymic epithelial cell line should facilitate the study of the molecular events responsible for very early stages of T cell development including T lymphocyte-lineage commitment.
Class switching and meiotic defects in mice lacking the E3 ubiquitin ligase RNF8
Authors: Margarida Almeida Santos, Michael S.Y. Huen, Mila Jankovic, Hua-Tang Chen, Andrés J. López-Contreras, Isaac A. Klein, Nancy Wong, Juan L.R. Barbancho, Oscar Fernandez-Capetillo, Michel C. Nussenzweig, Junjie Chen, André Nussenzweig
Journal: The Journal of Experimental Medicine (2010)

53BP1 is a well-known mediator of the cellular response to DNA damage. Two alternative mechanisms have been proposed to explain 53BP1’s interaction with DNA double-strand breaks (DSBs), one by binding to methylated histones and the other via an RNF8 E3 ligase–dependent ubiquitylation pathway. The formation of RNF8 and 53BP1 irradiation-induced foci are both dependent on histone H2AX. To evaluate the contribution of the RNF8-dependent pathway to 53BP1 function, we generated RNF8 knockout mice. We report that RNF8 deficiency results in defective class switch recombination (CSR) and accumulation of unresolved immunoglobulin heavy chain–associated DSBs. The CSR DSB repair defect is milder than that observed in the absence of 53BP1 but similar to that found in H2AX−/− mice. Moreover, similar to H2AX but different from 53BP1 deficiency, RNF8−/− males are sterile, and this is associated with defective ubiquitylation of the XY chromatin. Combined loss of H2AX and RNF8 does not cause further impairment in CSR, demonstrating that the two genes function epistatically. Importantly, although 53BP1 foci formation is RNF8 dependent, its binding to chromatin is preserved in the absence of RNF8. This suggests a two-step mechanism for 53BP1 association with chromatin in which constitutive loading is dependent on interactions with methylated histones, whereas DNA damage–inducible RNF8-dependent ubiquitylation allows its accumulation at damaged chromatin.
Effects of Exercise and Anemia on Coronary Arteries of Small Animals as Revealed by the Corrosion-Cast Technique
Authors: JAY TEPPERMAN, DAVID PEARLMAN
Journal: Circulation Research (1961)

Vinyl acetate corrosion casts were prepared of the coronary arterial trees of chronically exercised rats and of suitable control animals. In four experiments, there was a statistically significant increase in the mean coronary-cast weight of the exercised animals over that of controls. In two experiments, the coronary- cast/heart-weight ratios were significantly increased. In three-week-old ducklings rendered anemic by an iron-deficient diet, corrosion casts of the coronary vessels showed marked increases in cast weight, increase in size of homologous vessels, and generally more luxuriant arborization of the tree. No differences were found when coronary casts of thyroxin-injected or of pentaerythritol tetranitrate-injected rats were compared with those of control animals. Right-to-left-side coronary anastomoses were demonstrated in 75 per cent of guinea-pig hearts studied by the corrosion-cast technique. In five experiments, retrograde filling of a ligated anterior descending branch of the left coronary artery was demonstrated when the vinyl acetate solution was injected into the aorta.
Pulmonary manifestations of human herpesvirus-8 during HIV infection
Authors: Raphael Borie, Jacques Cadranel, Amélie Guihot, Anne Geneviève Marcelin, Lionel Galicier, Louis-Jean Couderc
Journal: European Respiratory Journal (2013)

Human herpesvirus (HHV)-8 is an oncogenic gamma herpesvirus that was first described in 1994 in Kaposi sarcoma lesions. HHV-8 is involved in the pathophysiological features of multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL), both rare B-cell lymphoproliferative diseases. HHV-8-related tumours occur almost exclusively in immunocompromised patients, mostly those with HIV infection. Combined antiretroviral therapies have reduced the incidence of Kaposi sarcoma but not MCD and PEL. HHV-8-related diseases frequently exhibit pulmonary involvement, which may indicate the disease. Kaposi sarcoma in the lung is often asymptomatic but may require specific therapy. It mostly shows cutaneous or mucosal involvement. Patients with typical MCD present fever and lymphadenopathy associated with interstitial lung disease without opportunistic infection. Specific treatment may be urgent. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without a pleural mass on computed tomography scan. Rapid diagnosis prevents unnecessary examinations and leads to specific, rapid treatment. Therapy is complex, combining antiretroviral therapy and chemotherapy.
Cyclic Nucleotide Phosphodiesterase 1C Promotes Human Arterial Smooth Muscle Cell Proliferation
Authors: Sergei D. Rybalkin, Irina Rybalkina, Joseph A. Beavo, Karin E. Bornfeldt
Journal: Circulation Research (2002)

Proliferation of arterial smooth muscle cells (SMCs) is a key event in the formation of advanced atherosclerotic lesions and restenosis after angioplasty. Cyclic nucleotides (cAMP and cGMP) inhibit arterial SMC proliferation, and elevation of cyclic nucleotides reduces neointimal formation after angioplasty in animal models. Degradation of cAMP and cGMP is catalyzed by cyclic nucleotide phosphodiesterases (PDEs). One of these, PDE1C, hydrolyzes cAMP and cGMP and is expressed in proliferating human SMCs but is absent in quiescent human aorta. Thus, PDE1C expression is low in cultured human SMCs made quiescent by attaching to fibrillar collagen type I. After release from the fibrillar collagen, PDE1C expression is induced and associated with traverse through S-phase of the cell cycle. Further, PDE1C is expressed in vivo in human fetal aorta containing proliferating SMCs, but not in newborn aorta in which SMC proliferation has ceased. Inhibition of PDE1C in SMCs isolated from normal aorta or from lesions of atherosclerosis using antisense oligonucleotides or a PDE1 inhibitor results in suppression of SMC proliferation. In conclusion, PDE1C expression is a marker of human SMC proliferation ex vivo and in vivo. Inhibition of PDE1C leads to inhibition of human SMC proliferation. Because PDE1C is absent in quiescent SMCs, PDE1C inhibitors may target proliferating SMCs in lesions of atherosclerosis or restenosis.
Magnetic resonance imaging, radiography, and scintigraphy of the finger joints: one year follow up of patients with early arthritis
Authors: M Klarlund
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To evaluate synovial membrane hypertrophy, tenosynovitis, and erosion development of the 2nd to 5th metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints by magnetic resonance imaging in a group of patients with rheumatoid arthritis (RA) or suspected RA followed up for one year. Additionally, to compare the results with radiography, bone scintigraphy, and clinical findings. <h3>PATIENTS AND METHODS</h3> Fifty five patients were examined at baseline, of whom 34 were followed up for one year. Twenty one patients already fulfilled the American College of Rheumatology (ACR) criteria for RA at baseline, five fulfilled the criteria only after one year9s follow up, whereas eight maintained the original diagnosis of early unclassified polyarthritis. The following MRI variables were assessed at baseline and one year: synovial membrane hypertrophy score, number of erosions, and tenosynovitis score. <h3>RESULTS</h3> MRI detected progression of erosions earlier and more often than did radiography of the same joints; at baseline the MRI to radiography ratio was 28:4. Erosions were exclusively found in patients with RA at baseline or fulfilling the ACR criteria at one year. At one year follow up, scores of MR synovial membrane hypertrophy, tenosynovitis, and scintigraphic tracer accumulation had not changed significantly from baseline; in contrast, swollen and tender joint counts had declined significantly (p&lt;0.05). <h3>CONCLUSIONS</h3> MRI detected more erosions than radiography. MR synovial membrane hypertrophy and scintigraphy scores did not parallel the changes seen over time in clinically assessed swollen and tender joint counts. Although joint disease activity may be assessed as quiescent by conventional clinical methods, a more detailed evaluation by MRI may show that a pathological condition is still present within the synovium.
The DNA Damage Response Arouses the Immune System
Authors: Stephan Gasser, David H. Raulet
Journal: Cancer Research (2006)

Abstract Although there is considerable knowledge of how DNA damage triggers cell cycle arrest, DNA repair, and apoptosis, little was known about its potential role in immune responses. Recently, we showed that genotoxic stress and stalled DNA replication forks induce the expression of ligands for the NKG2D receptor found in natural killer cells and certain T cells, cell types that are able to attack tumor cells. Chronic activation of this response in tumor cells may contribute to immune recognition, but it also imposes a selection mechanism for immune escape and malignant progression. This unique arm of the DNA damage response may have implications for understanding therapeutic responses, many of which induce the DNA damage response, and for designing more effective regimens to treat cancer. (Cancer Res 2006; 66(8): 3959-62)
Insights in dynamic kinome reprogramming as a consequence of MEK inhibition in MLL-rearranged AML
Authors: K R Kampen, A ter Elst, H Mahmud, F J G Scherpen, S H Diks, M P Peppelenbosch, V de Haas, V Guryev, E S J M de Bont
Journal: Leukemia (2013)
SERUM SICKNESS IN RABBITS
Authors: Mover S. Fleisher, Lloyd Jones
Journal: The Journal of Experimental Medicine (1931)

1. The injection of a single large dose of normal horse serum into rabbits results in the appearance 3 to 8 days later of erythematous and edematous reactions on the ears in 68.9 per cent of the animals. 2. The injections may be given by any of several routes and reactions appear when the site of injection is definitely distant from the ears. 3. Injections of various antisera into rabbits cause the appearance of similar reactions. 4. These reactions can be considered as manifestations of serum sickness in rabbits.
What do adult squash players think about protective eyewear?
Authors: C Finch, P Vear
Journal: British Journal of Sports Medicine (1998)

OBJECTIVE: To determine the attitudes of adult squash players towards protective eyewear. METHODS: A survey of 197 competition and social squash players from seven squash centres in the outer eastern suburbs of Melbourne, Australia was conducted in September to October 1995. Information about participation in squash, previous injuries, use of protective eyewear, barriers towards eyewear use, and attitudes towards protective eyewear was obtained by a self report questionnaire. RESULTS: Squash is a popular sport in Australia. Of the players surveyed, 6% played in junior competitions, 67% in senior competitions, and 27% were social players. Most had been playing for more than ten years. Some 15% of players had previously suffered an eye injury, most commonly caused by a racquet. Less than 10% of players reported that they wore protective eyewear when they played squash, and 35% of these wore prescriptive lenses which they considered to be protective. The major reason for not wearing protective eyewear was the perception that it was unnecessary. Poor vision and a lack of comfort were also stated as reasons by a significant number of players. More than half (57%) of the respondents agreed that more players should wear protective eyewear, yet only 16% thought it should be compulsory for all players. There was considerable support for protective eyewear use by junior players, however. CONCLUSIONS: The rate of protective eyewear use is low among competition and social squash players in Melbourne. The major areas that need to be addressed are the ignorance of the need for protective eyewear among social and experienced players and the mistaken belief that prescription lenses provide adequate protection on a squash court.
Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients
Authors: Yves Bécouarn, Erick Gamelin, Bruno Coudert, Sylvie Négrier, Jean-Yves Pierga, Jean-Luc Raoul, Jocelyne Provençal, Olivier Rixe, Claude Krisch, Caroline Germa, Mohamed Bekradda, Dominique Mignard, Mireille Mousseau
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess antitumor activity and safety of two regimens in advanced colorectal cancer (CRC) patients with proven fluorouracil (5-FU) resistance in a randomized phase II study: 5-FU/folinic acid (FA) combined with alternating irinotecan (also called CPT-11) and oxaliplatin (FC/FO tritherapy), and an oxaliplatin/irinotecan (OC) combination. PATIENTS AND METHODS: Sixty-two patients were treated: arm FC/FO (32 patients) received, every 4 weeks, FA 200 mg/m 2 followed by a 400-mg/m 2 5-FU bolus injection, then a 600-mg/m 2 continuous infusion of 5-FU on days 1 and 2 every 2 weeks administered alternately with irinotecan (180 mg/m 2 on day 1) and oxaliplatin (85 mg/m 2 on day 15). Arm OC (30 patients) received oxaliplatin 85 mg/m 2 and irinotecan 200 mg/m 2 every 3 weeks. RESULTS: In an intent-to-treat analysis, two partial responses lasting 10.7 and 16 months were observed with the tritherapy regimen, and seven (median duration, 11 months; range, 10.6 to 11.4 months) were observed with the bitherapy regimen. Median progression-free and overall survival times were 8.2 and 9.8 months, respectively, in the FC/FO arm and 8.5 and 12.3 months, respectively, in the OC arm. Main grade 3/4 toxicities were, respectively, neutropenia, 53% and 47%; febrile neutropenia, 13% and 3%; diarrhea, 19% and 10%; vomiting, 6% and 13%; and neurosensory toxicity, 3% and 3%. No treatment-related deaths occurred. CONCLUSION: The every-3-weeks OC combination is safe and active in advanced 5-FU–resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.