tbuckley/cabot-search huggingface dataset:
Government plans to move back from local to central decision making in social care
Authors: A. O'Dowd
Journal: BMJ (2010)

Decisions on social care may be made more centrally in a notable change to the current UK government policy to encourage devolution in health care, MPs were told this week.

England’s health secretary, Andy Burnham, told MPs on the parliamentary health select committee that people want clarity and fairness rather than too much local discretion on how services are provided.

The committee, quizzing Mr Burnham as part of its inquiry into social care, asked about the forthcoming social care white paper, expected this spring before the general election.

The government published its green paper, Shaping the Future of Care Together , in July last year with the intention of reforming the funding and delivery of …
Subacromial ultrasound guided or systemic steroid injection for rotator cuff disease: randomised double blind study
Authors: O. M Ekeberg, E. Bautz-Holter, E. K Tveita, N. G Juel, S. Kvalheim, J. I Brox
Journal: BMJ (2009)

<b>Objective</b> To compare the effectiveness of ultrasound guided corticosteroid injection in the subacromial bursa with systemic corticosteroid injection in patients with rotator cuff disease. <b>Design</b> Double blind randomised clinical trial. <b>Setting</b> Outpatient clinic of a physical medicine and rehabilitation department in Oslo, Norway. <b>Patients</b> 106 patients with rotator cuff disease lasting at least three months. <b>Interventions</b> Ultrasound guided corticosteroid and lidocaine injection in the subacromial bursa and lidocaine injection in the gluteal region (local group); corticosteroid and lidocaine injection in the gluteal region and ultrasound guided lidocaine injection in the subacromial bursa (systemic group). <b>Main outcome measures</b> Difference in improvement in the overall shoulder pain and disability index score after six weeks. <b>Results</b> Six weeks after the intervention, the mean difference in improvement in overall shoulder pain and disability index score between the local group and the systemic group was −5.2 (95% confidence interval −13.9 to 3.5); it was −4.1 (−12.3 to 4.1, P=0.32) after adjustment for baseline score. A small but statistically significant difference in improvement between groups occurred in favour of the local group for two secondary outcome measures: the Western Ontario rotator cuff index (8.1, 0.7 to 15.6) and change in main complaint (2.0, 0 to 4). <b>Conclusions</b> No important differences in short term outcomes were found between local ultrasound guided corticosteroid injection and systemic corticosteroid injection in rotator cuff disease. <b>Trial registration</b> Clinical trials NCT00640575.
Respiratory function in patients with thalassaemia and iron overload
Authors: I Dimopoulou, DT Kremastinos, TG Maris, S Mavrogeni, GE Tzelepis
Journal: European Respiratory Journal (1999)

Iron deposition in the respiratory system has been proposed as a potential cause of the ventilatory restrictive impairment seen in patients with thalassaemia major (TM) and iron overload. In this study, magnetic resonance imaging (MRI) measurements of the liver (T2 relaxation time) were used as a surrogate index of total body iron burden and the extent to which these measurements correlated with total lung capacity (TLC) in patients with TM was examined. Twenty-one patients (aged 25+/-5 yrs) with TM participated in the study. Standard pulmonary function tests were undertaken and the T2 relaxation time of the liver was measured in all patients. Ventilatory restrictive impairment (mean TLC 74+/-11 (SD)% predicted) was the most common abnormality found in 71% of TM patients. There was no correlation between TLC (% pred) and T2 relaxation time (r=0.06, p=0.78). T2 relaxation time correlated weakly with average serum ferritin levels (r=-0.56, p=0.008). In conclusion, the data do not support the notion that the restrictive impairment in patients with thalassaemia major and iron overload is related to iron deposition in the respiratory system.
Major histocompatibility complex-restricted recognition of retroviral superantigens by V beta 17+ T cells.
Authors: M A Blackman, F E Lund, S Surman, R B Corley, D L Woodland
Journal: The Journal of Experimental Medicine (1992)

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.
Hepatitis C Virus Seropositivity in Organ Donors and Survival in Heart Transplant Recipients
Authors: Leanne B Gasink, Emily A Blumberg, A Russell Localio, Shashank S Desai, Ajay K Israni, Ebbing Lautenbach
Journal: JAMA (2006)

ContextAlthough liberalization of donor criteria could expand the donor pool, the use of certain “marginal donors,” such as those who are hepatitis C virus (HCV) positive, is controversial. Little is known about the effect of donor HCV positivity on survival in cardiac transplantation.ObjectivesTo examine the association between donor HCV positivity and survival among heart transplant recipients and to determine the effects of recipient age and recipient HCV status on this association.Design, Setting, and ParticipantsA multicenter cohort study was performed using the US Scientific Registry of Transplant Recipients. Adult heart transplant patients who received their transplants between April 1, 1994, and July 31, 2003, were eligible for inclusion.Main Outcome MeasureAll-cause mortality.ResultsOf 10 915 patients meeting entry criteria, 261 received an HCV-positive donor heart. Mortality was higher among recipients of HCV-positive donor hearts at 1 year (16.9% vs 8.2%; P&lt;.001), 5 years (41.8% vs 18.5%; P&lt;.001), and 10 years (50.6% vs 24.3%; P&lt;.001). Using Kaplan-Meier methods, 1-, 5-, and 10-year survival rates were 83%, 53%, and 25%, and 92%, 77%, and 53% for recipients of HCV-positive and HCV-negative donor hearts, respectively (P&lt;.001, log-rank test). Recipients of HCV-positive donor hearts were more likely to die of liver disease and coronary vasculopathy. After propensity matching, the overall hazard ratio (HR) associated with receipt of an HCV-positive donor heart was 2.10 (95% confidence interval [CI], 1.60-2.75). Stratified analyses showed that HRs did not vary by recipient HCV status or by recipient age (for recipients aged 18-39 years: HR, 1.75 [95% CI, 0.70-4.40]; for recipients aged 40-59 years: HR, 2.23 [95% CI, 1.42-3.52]; and for recipients aged 60 years and older: HR, 2.07 [95% CI, 1.32-3.27]; overall P value for interaction, &gt;.10).ConclusionsReceipt of a heart from an HCV-positive donor is associated with decreased survival in heart transplant recipients. This association appears to be independent of recipient HCV status and age. Preferential allocation of HCV-positive donors to HCV-positive recipients and/or older recipients is not warranted.
Development of a Standardized Set of Patient-centered Outcomes for Advanced Prostate Cancer: An International Effort for a Unified Approach
Authors: Alicia K. Morgans, Annelotte C.M. van Bommel, Caleb Stowell, Janet L. Abrahm, Ethan Basch, Justin E. Bekelman, Donna L. Berry, Alberto Bossi, Ian D. Davis, Theo M. de Reijke, Louis J. Denis, Sue M. Evans, Neil E. Fleshner, Daniel J. George, Jim Kiefert, Daniel W. Lin, Andrew G. Matthew, Ray McDermott, Heather Payne, Ian A.G. Roos, Deborah Schrag, Thomas Steuber, Bertrand Tombal, Jean-Paul van Basten, Jacobus J.M. van der Hoeven, David F. Penson
Journal: European Urology (2015)

There are no universally monitored outcomes relevant to men with advanced prostate cancer, making it challenging to compare health outcomes between populations. We sought to develop a standard set of outcomes relevant to men with advanced prostate cancer to follow during routine clinical care. The International Consortium for Health Outcomes Measurement assembled a multidisciplinary working group to develop the set. We used a modified Delphi method to achieve consensus regarding the outcomes, measures, and case mix factors included. The 25 members of the multidisciplinary international working group represented academic and nonacademic centers, registries, and patients. Recognizing the heterogeneity of men with advanced prostate cancer, the group defined the scope as men with all stages of incurable prostate cancer (metastatic and biochemical recurrence ineligible for further curative therapy). We defined outcomes important to all men, such as overall survival, and measures specific to subgroups, such as time to metastasis. Measures gathered from clinical data include measures of disease control. We also identified patient-reported outcome measures (PROMs), such as degree of urinary, bowel, and erectile dysfunction, mood symptoms, and pain control. The international multidisciplinary group identified clinical data and PROMs that serve as a basis for international health outcome comparisons and quality-of-care assessments. The set will be revised annually. Our international group has recommended a standardized set of patient-centered outcomes to be followed during routine care for all men with advanced prostate cancer.
Characterization of nonlymphoid cells derived from rat peripheral lymph
Authors: CW Pugh, GG MacPherson, HW Steer
Journal: The Journal of Experimental Medicine (1983)

Mesenteric lymphadenectomy in rats is followed by union of peripheral and central lymphatics, allowing the collection of intestine-derived peripheral lymph cells via the thoracic duct for several days. These cells include a proportion of nonlymphoid cells (NLC) that show irregular and heterogeneous surface morphology including long pseudopodia and veils. They stain variably for nonspecific esterase and acid phosphatase and are ATPase-positive. Their nuclei are irregular and some contain cytoplasmic inclusions, some of which show peroxidase activity and/or contain DNA. NLC have a range of densitites generally lower than that of lymphocytes. Freshly collected NLC express the leukocyte-common antigen (defined by monoclonal antibody MRC Ox 1) and Ia antigens (I-A and I-E subregion products defined by monoclonal antibodies) but they show a relative lack of other surface markers normally found on rat B or T lymphocytes (W3/13, W3/25, MRC Ox 12 (sIg), MRC Ox 19) or rat macrophages (FcR, C'R, mannose R, W3/25). In general NLC are only weakly adherent to glass or plastic. Although a subpopulation of NLC appear to have had a phagocytic past, freshly collected NLC fail to phagocytose a variety of test particles in vitro. NLC also appear incapable of pinocytosis in vitro. This heterogeneity may represent distinct subpopulations of NLC or different stages in the development of a single cell lineage. Direct cannulation of mesenteric lacteals shows that the majority of NLC are derived from the small intestine and their precursors appear to be present both in lamina propria and Peyer's patches. Kinetic studies, following irradiation or intravenous tritiated thymidine, show that the majority of NLC turn over rapidly in the intestine with a modal time of 3-5 d. Studies with bone marrow chimeras show that they are derived from a rapidly dividing precursor present in normal bone marrow. NLC occur at very low frequencies in normal thoracic duct lymph at all times following cannulation. The evidence presented suggests that NLC closely resemble mouse lymphoid dendritic cells. This conclusion is supported by evidence already obtained showing that NLC are potent stimulators of the semi-allogeneic rat primary mixed leukocyte reaction. In addition to the ceils resembling dendritic cells rare monocytoid cells are found in thoracic duct lymph of lymphadenectomized specific pathogen-free rats. The proportion of these cells increases greatly when the animals are conventionally housed. It seems probable that the physiological function of NLC is to act as accessory cells in the lymph nodes to which they normally drain. Methods for enriching NLC and thus facilitating analysis of their functions are discussed.
Generation of PLZF+ CD4+ T cells via MHC class II–dependent thymocyte–thymocyte interaction is a physiological process in humans
Authors: You Jeong Lee, Yoon Kyung Jeon, Byung Hyun Kang, Doo Hyun Chung, Chung-Gyu Park, Hee Young Shin, Kyeong Cheon Jung, Seong Hoe Park
Journal: The Journal of Experimental Medicine (2009)

Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II–expressing thymocytes (thymocyte–thymocyte [T–T] interactions) with a transgenic mouse system. However, the developmental dissection of this T–T interaction in humans has not been possible because of the lack of known cellular molecules specific for T–T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T–T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II–dependent T–T interaction.
Predicting survival in pulmonary arterial hypertension in the UK
Authors: Wai-Ting Nicola Lee, Yi Ling, Karen K. Sheares, Joanna Pepke-Zaba, Andrew John Peacock, Martin Keith Johnson
Journal: European Respiratory Journal (2012)

Contemporary prognostic equations in pulmonary arterial hypertension (PAH) derived from US and French cohorts may not perform as well in the UK as a locally derived scoring scheme. The aim of the study was to develop and validate a UK risk score to predict prognosis in PAH. Baseline mortality predictors identified by multivariate Cox analysis in 182 incident PAH patients were used to derive the Scottish composite score (SCS). Its prognostic performance in an independent UK cohort was compared with the French registry and Pulmonary Hypertension Connection (PHC) registry equations using Brier scores (BS). The SCS based on age, sex, aetiology, right atrial pressure, cardiac output and 6-min walk distance predicted survival in the validation cohort (hazard ratio (HR) 1.7 per point increase; p&lt;0.001) and provided further prognostic stratification in World Health Organization (WHO) functional class III patients (HR 1.8 per point increase; p&lt;0.001). It was more accurate than the French registry equation in predicting 1-yr survival (BS: 0.092 <i>versus</i> 0.146; p=0.001) and 2-yr survival (0.131 <i>versus</i> 0.255; p&lt;0.001). There was no significant difference in BS between the SCS and PHC registry equation. The SCS predicts survival and can be used to supplement WHO functional class in prognostication.
RNA Dysregulation in Diseases of Motor Neurons
Authors: Fadia Ibrahim, Tadashi Nakaya, Zissimos Mourelatos
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Motor neuron diseases (MNDs) are neurodegenerative disorders that lead to paralysis and typically carry a dismal prognosis. In children, inherited spinal muscular atrophies are the predominant diseases that affect motor neurons, whereas in adults, amyotrophic lateral sclerosis, which is inherited but mostly sporadic, is the most common MND. In recent years, we have witnessed a revolution in this field, sparked by the discovery of the genes that cause MNDs. Remarkably, at least 10 genes, whose products are either RNA-binding proteins or proteins that function in RNA processing and regulation, cause MNDs and place the dysregulation of RNA pathways at the center of motor neuron degeneration pathogenesis.
Disease-Free Survival According to Degree of <i>HER2</i> Amplification for Patients Treated With Adjuvant Chemotherapy With or Without 1 Year of Trastuzumab: The HERA Trial
Authors: Mitch Dowsett, Marion Procter, Worta McCaskill-Stevens, Evandro de Azambuja, Urania Dafni, Josef Rueschoff, Bruce Jordan, Stella Dolci, Mark Abramovitz, Oliver Stoss, Giuseppe Viale, Richard D. Gelber, Martine Piccart-Gebhart, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2009)

To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy.IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up.Central FISH results were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) HER2 copy number, or (3) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab.There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy.
Prescription of beta‐blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival
Authors: Daniela Dobre, Dirk J. van Veldhuisen, Mike J.L. DeJongste, Carolien Lucas, Ger Cleuren, Robbert Sanderman, Adelita V. Ranchor, Flora M. Haaijer‐Ruskamp
Journal: European Journal of Heart Failure (2006)
Natural peptides selected by diabetogenic DQ8 and murine I-Ag7 molecules show common sequence specificity
Authors: A. Suri
Journal: Journal of Clinical Investigation (2005)

In this study, a large number of naturally processed peptides was isolated and identified from the human diabetes-susceptible class II MHC molecules HLA-DQ8 (DQA1*0301,DQB1*0302) and from murine I-A species, both of which are expressed in genetically identical APC lines. The peptides presented during the processing of autologous proteins were highly selective in showing sequence specificity, mainly consisting of 1 or more acidic residues at their C terminus. Testing for binding to the MHC molecules revealed that the position 9 (P9) acidic residues of the peptides contributed decisively to binding. For HLA-DQ8, the P1 residue, which was also an acidic amino acid, influenced binding positively. Both HLA-DQ8 and I-A(g7) selected for common peptides that bound in the same register. There was no evidence for selection of peptides having nonspecific or promiscuous binding. Thus, diabetogenic class II MHC molecules are highly selective in terms of the peptides presented by their APCs, and this is governed by the features of their P9 anchor pocket. These results are in striking contrast to those from studies examining synthetic peptide or phage display libraries, in which many peptides were shown to bind.
Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium
Authors: Gretchen L. Gierach, Laura Ichikawa, Karla Kerlikowske, Louise A. Brinton, Ghada N. Farhat, Pamela M. Vacek, Donald L. Weaver, Catherine Schairer, Stephen H. Taplin, Mark E. Sherman
Journal: JNCI Journal of the National Cancer Institute (2012)

Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors.We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 1996-2005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided.A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0 cm (HR = 1.55, 95% CI = 1.14 to 2.09).High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed.