tbuckley/cabot-search huggingface dataset:
NHS England and Monitor offer compromise deal to hospitals on payments for procedures
Authors: M. Limb
Journal: BMJ (2015)

Healthcare leaders have given a cautious welcome to a “pragmatic” new offer from NHS England and Monitor to settle uncertainty over tariff payments for 2015-16.

But hospital and commissioner organisations said that the interim “compromise” was far from ideal and that payment systems must still be overhauled to be sustainable in the future.

The latest offer would boost providers’ income overall by £500m (€680m; $769m) more than a previous proposal that most hospitals had rejected.1 This includes reduced efficiency targets and £130m towards the cost of emergency hospital admissions.

Earlier this year most NHS hospitals in England rejected the proposed national payment tariff for 2015-16, saying that the terms would leave them unable to guarantee “sustainable and safe care.”1 Monitor and NHS England have now reconsidered the offer, and on 19 February they issued an enhanced tariff option for 2015-16.

NHS England said that it would “ultimately” bear most of the extra costs and give clinical commissioning groups (CCGs) as much as £150m in support to offset additional pressures that …
COMPLEMENT DEFICIENCY AND CHROMOSOMAL BREAKS IN A CASE OF SWISS-TYPE AGAMMAGLOBULINÆMIA
Authors: JerryC. Jacobs, W.A. Blanc, A.De Capoa, W.C. Heird, E. McGilvray, O.J. Miller, J.H. Morse, R.D. Rossen, J.N. Schullinger, R.A. Walzer
Journal: The Lancet (1968)
Estimates of Global Prevalence of Childhood Underweight in 1990 and 2015
Authors: Mercedes de Onis
Journal: JAMA (2004)

One key target of the United Nations Millennium Development goals is to reduce the prevalence of underweight among children younger than 5 years by half between 1990 and 2015.To estimate trends in childhood underweight by geographic regions of the world.Time series study of prevalence of underweight, defined as weight 2 SDs below the mean weight for age of the National Center for Health Statistics and World Health Organization (WHO) reference population. National prevalence rates derived from the WHO Global Database on Child Growth and Malnutrition, which includes data on approximately 31 million children younger than 5 years who participated in 419 national nutritional surveys in 139 countries from 1965 through 2002.Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight children by region in 1990 and 2015 and to calculate the changes (ie, increase or decrease) to these values between 1990 and 2015.Worldwide, underweight prevalence was projected to decline from 26.5% in 1990 to 17.6% in 2015, a change of -34% (95% confidence interval [CI], -43% to -23%). In developed countries, the prevalence was estimated to decrease from 1.6% to 0.9%, a change of -41% (95% CI, -92% to 343%). In developing regions, the prevalence was forecasted to decline from 30.2% to 19.3%, a change of -36% (95% CI, -45% to -26%). In Africa, the prevalence of underweight was forecasted to increase from 24.0% to 26.8%, a change of 12% (95% CI, 8%-16%). In Asia, the prevalence was estimated to decrease from 35.1% to 18.5%, a change of -47% (95% CI, -58% to -34%). Worldwide, the number of underweight children was projected to decline from 163.8 million in 1990 to 113.4 million in 2015, a change of -31% (95% CI, -40% to -20%). Numbers are projected to decrease in all subregions except the subregions of sub-Saharan, Eastern, Middle, and Western Africa, which are expected to experience substantial increases in the number of underweight children.An overall improvement in the global situation is anticipated; however, neither the world as a whole, nor the developing regions, are expected to achieve the Millennium Development goals. This is largely due to the deteriorating situation in Africa where all subregions, except Northern Africa, are expected to fail to meet the goal.
Independent and Opposing Roles For Btk and Lyn in B and Myeloid Signaling Pathways
Authors: Anne B. Satterthwaite, Clifford A. Lowell, Wasif N. Khan, Paschalis Sideras, Frederick W. Alt, Owen N. Witte
Journal: The Journal of Experimental Medicine (1998)

Transphosphorylation by Src family kinases is required for the activation of Bruton's tyrosine kinase (Btk). Differences in the phenotypes of Btk-/- and lyn-/- mice suggest that these kinases may also have independent or opposing functions. B cell development and function were examined in Btk-/-lyn-/- mice to better understand the functional interaction of Btk and Lyn in vivo. The antigen-independent phase of B lymphopoiesis was normal in Btk-/-lyn-/- mice. However, Btk-/-lyn-/- animals had a more severe immunodeficiency than Btk-/- mice. B cell numbers and response to T cell-dependent antigens were reduced. Btk and Lyn therefore play independent or partially redundant roles in the maintenance and function of peripheral B cells. Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice. A transgene expressing Btk at approximately 25% of endogenous levels (Btklo) was crossed onto Btk-/- and Btk-/-lyn-/- backgrounds to demonstrate that Btk is limiting for BCR signaling in the presence but not in the absence of Lyn. These observations indicate that the net outcome of Lyn function in vivo is to inhibit Btk-dependent pathways in B and myeloid cells, and that Btklo mice are a useful sensitized system to identify regulatory components of Btk signaling pathways.
Correlation of Alcohol Craving With Striatal Dopamine Synthesis Capacity and D<sub>2/3</sub>Receptor Availability: A Combined [<sup>18</sup>F]DOPA and [<sup>18</sup>F]DMFP PET Study in Detoxified Alcoholic Patients
Authors: Andreas Heinz, Thomas Siessmeier, Jana Wrase, Hans Georg Buchholz, Gerhard Gründer, Yoshitaka Kumakura, Paul Cumming, Mathias Schreckenberger, Michael N. Smolka, Frank Rösch, Karl Mann, Peter Bartenstein
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: In abstinent alcoholic patients, a low availability of dopamine D2/3 receptors in the ventral striatum and adjacent putamen was associated with a high level of craving for alcohol. Alcohol craving may also depend on presynaptic dysfunction of striatal dopamine production, which may contribute to the risk of relapse. In this study, positron emission tomography (PET) was used to compare dopamine synthesis capacity in the striatum in alcoholic patients and healthy comparison subjects. METHOD: Positron emission tomography (PET) was used to map the net blood-brain clearance of the dopa decarboxylase substrate 6-[18F]fluoro-l-dopa, an index of dopamine synthesis capacity, in the striatum of 12 detoxified male alcoholic patients and 13 age-matched healthy men. The parametric maps were correlated with results of an earlier [18F]desmethoxyfallypride PET study of dopamine D2/3 receptor availability in the same 12 alcoholic patients and in 12 of the healthy volunteers. Alcohol craving was measured with the Alcohol Craving Questionnaire. Patients were followed for 6 months, and alcohol intake was recorded. RESULTS: The magnitude of net blood-brain clearance in the striatum did not differ significantly between detoxified alcoholic patients and the comparison subjects. However, a voxel-wise correlation analysis of net blood-brain clearance in the alcoholic patients linked low levels of dopamine synthesis capacity in the bilateral putamen with high levels of alcohol craving. After normalization of net blood-brain clearance maps to the voxel-wise estimates of dopamine D2/3 receptor availability, there was still a negative correlation with alcohol craving. Alcohol craving at the time of scanning was associated with high level of alcohol intake in the 6-month follow-up period. CONCLUSIONS: Simultaneous assay by PET of pre- and postsynaptic markers of dopamine neurotransmission indicated that a striatal dopamine deficit correlated with alcohol craving, which was associated with a high relapse risk.
The Composition of the F tal Urine Secreted in Utero
Authors: T. A. Helme
Journal: BMJ (1893)

COMPOSITION OF FCETAL URINE.r 1261 specimen 1.-I ounce.Specimen Il.-6 drachms.Passed immediately after birth, and Eight and a-half hours after before inspiration.birth.Examination showed-EXaMination showed- No sugar.No sugar.No albumen.No albumen.No phosphates.No phosphates.No sulphates.Sulphates present
Agricultural pesticide use in California: pesticide prioritization, use densities, and population distributions for a childhood cancer study.
Authors: R B Gunier, M E Harnly, P Reynolds, A Hertz, J Von Behren
Journal: Environmental Health Perspectives (2001)

Several studies have suggested an association between childhood cancer and pesticide exposure. California leads the nation in agricultural pesticide use. A mandatory reporting system for all agricultural pesticide use in the state provides information on the active ingredient, amount used, and location. We calculated pesticide use density to quantify agricultural pesticide use in California block groups for a childhood cancer study. Pesticides with similar toxicologic properties (probable carcinogens, possible carcinogens, genotoxic compounds, and developmental or reproductive toxicants) were grouped together for this analysis. To prioritize pesticides, we weighted pesticide use by the carcinogenic and exposure potential of each compound. The top-ranking individual pesticides were propargite, methyl bromide, and trifluralin. We used a geographic information system to calculate pesticide use density in pounds per square mile of total land area for all United States census-block groups in the state. Most block groups (77%) averaged less than 1 pound per square mile of use for 1991-1994 for pesticides classified as probable human carcinogens. However, at the high end of use density (> 90th percentile), there were 493 block groups with more than 569 pounds per square mile. Approximately 170,000 children under 15 years of age were living in these block groups in 1990. The distribution of agricultural pesticide use and number of potentially exposed children suggests that pesticide use density would be of value for a study of childhood cancer.
Non-Hodgkin's lymphoma after immunosuppressive therapy
Authors: L J KINLEN
Journal: Gut (2000)

See article on page 514 

The development of renal transplantation in the 1960s, made possible by azathiopine, also allowed the testing of the immunosurveillance proposed by Burnett and Thomas, that cancer has its origins in mutations which would usually be eliminated by a healthy immune system. An increased incidence of non-Hodgkin's lymphoma (NHL) in transplant recipients was soon recognised but not the generalised increases of malignancy that seemed to be predicted by the theory. Instead, increases of skin, liver, and (possibly) cervix cancers, and of Kaposi's sarcoma suggested that immunosurveillance operates primarily against malignancies of infective origin, as animal work had also indicated. It has become clear that this hazard is a feature of other immunosuppressive drugs, including 6-mercaptopurine, cyclophosphamide, cyclosporine, and methotrexate, and is not dependent on the presence of foreign antigens, extending to patients without organ transplants. In fact, an increased incidence of NHL has been found in virtually every type of marked immune impairment (whether or not treatment related) that has been studied in appreciable numbers, included AIDS and rare genetically determined disorders such as the Wiskott Aldrich syndrome.1 

The paper by Farrell and colleagues2 in this issue of Gut on the risk of cancer in 782 patients …
Matrix metalloproteinase 3 is regulated by the laminin LAMA4 in human osteoarthritis
Authors: F C Fuerst, S M Kielhauser, G Gruber, M H Stradner, H Angerer, M L Kremser, D Setzagel, W B Graninger
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Osteoarthritis (OA) is characterised by a loss of cartilage extracellular matrix and chondrocyte hypertrophy. Syndecan 4 was shown to regulate ADAMTS5 and matrix metalloproteinase 3 (MMP3) which is crucial for cartilage breakdown. Syndecans have a binding site for laminins like LAMA4. Therefore the authors examined the expression and function of LAMA4 in OA cartilage. <h3>Methods</h3> The authors collected osteoarthritic cartilage specimen (n=20) from patients undergoing total knee replacement and performed immunohistochemistry for Syndecan 4 and LAMA4. Furthermore human chondrocytes cultures were treated with the LAMA4 blocking antibody 2A3 and gene expression of MMP3, MMP13, ADAMTS5, LAMA4 and Syndecan 4 was measured using RT-PCR. <h3>Results</h3> LAMA4 and Syndecan 4 are specifically co-expressed in hypertrophic chondrocyte clusters. Compared to sections from low-grade OA LAMA4 staining is significantly stronger in high-grade OA. Blocking LAMA4 in vitro leads to a significant (p&lt;0.03) suppression of MMP3 expression. <h3>Conclusion</h3> LAMA4 is expressed selectively in high-grade OA and regulates expression of MMP3 presumably via syndecan 4.
Serum Mannose-Binding Lectin Is a Strong Biomarker of Diabetic Retinopathy in Chinese Patients With Diabetes
Authors: Peiliang Geng, Yuanyuan Ding, Lin Qiu, Yinying Lu
Journal: Diabetes Care (2015)

OBJECTIVE Inflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We investigated serum MBL levels in patients with diabetes with and without diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS Serum MBL levels were determined in 348 patients with diabetes and in 100 healthy control subjects. The prediction value of MBL was compared with diabetes duration, hs-CRP, and other known predictors. Multivariate analyses were performed using logistic regression models. RESULTS MBL levels on admission were significantly increased in patients with diabetes with DR (P &amp;lt; 0.0001) and vision-threatening DR (VTDR; P &amp;lt; 0.0001). Multivariate logistic regression analysis adjusted for common indictors showed that serum MBL levels ≥3,385 μg/L were an independent predictor of DR (odds ratio [OR] 3.14, 95% CI 1.77–5.57) and VTDR (OR 7.83, 95% CI 3.35–18.31). The area under the receiver operating characteristic curve of MBL was 0.81 (95% CI 0.76–0.86) for DR and 0.84 (95% CI 0.74–0.93) for VTDR. CONCLUSIONS The current study demonstrated that MBL appears to be an independent biomarker for DR in the Chinese population, suggesting a possible role of MBL in the pathogenesis of DR complications in diabetes.
GPs will see little disruption in forthcoming NHS reforms, health secretary says
Authors: A. O'Dowd
Journal: BMJ (2010)

GPs will not suffer excessive disruption when they take control of most of the NHS budget as part of the government’s shake up of the health service, England’s health secretary has said.

Andrew Lansley, giving evidence to the parliamentary health select committee on 20 July in a one-off evidence session, said that doctors were looking forward to the changes as an “empowerment,” not as an “upheaval.”

MPs on the new health select committee—formed since the UK general election in May—quizzed Mr Lansley about the impact of the white paper published earlier this month ( BMJ 2010;341:c3796, 14 Jul, doi:10.1136/bmj.c3796), which set out how GPs will be given more responsibility for spending as primary care …
Genes, stem cells and biological pacemakers
Authors: Michael R Rosen, Peter R Brink, Ira S Cohen, Richard B Robinson
Journal: Cardiovascular Research (2004)

The advent of gene therapy and cell therapy has led to reconsideration of standard therapies for cardiac disease. One such area of reconsideration is that of the cardiac pacemaker, which has been the mainstay of treatment for high-degree heart block and sinoatrial node dysfunction. Over the past five years, gene therapy has been used to explore the overexpression of β2-adrenergic receptors, the down-regulation of inward rectifier current, and the overexpression of pacemaker current as potential sources of biological pacemakers. Cell therapy approaches have explored the “forcing” of embryonic stem cells to evolve along cardiac (and specifically pacemaker) cell lines and the use of adult mesenchymal stem cells as platforms for delivery of specific gene therapies. This review considers the strengths and weaknesses of each of the approaches used to date and attempts to look to the future of biological alternatives to electronic pacemakers.
Activated MET Is a Molecular Prognosticator and Potential Therapeutic Target for Malignant Peripheral Nerve Sheath Tumors
Authors: Keila E. Torres, Quan-Sheng Zhu, Katelynn Bill, Gonzalo Lopez, Markus P. Ghadimi, Xianbiao Xie, Eric D. Young, Juehui Liu, Theresa Nguyen, Svetlana Bolshakov, Roman Belousov, Suizhau Wang, Guy Lahat, Jun Liu, Belinda Hernandez, Alexander J. Lazar, Dina Lev
Journal: Clinical Cancer Research (2011)

Abstract Purpose: MET signaling has been suggested a potential role in malignant peripheral nerve sheath tumors (MPNST). Here, MET function and blockade were preclinically assessed. Experimental Design: Expression levels of MET, its ligand hepatocyte growth factor (HGF), and phosphorylated MET (pMET) were examined in a clinically annotated MPNST tissue microarray (TMA) incorporating univariable and multivariable statistical analyses. Human MPNST cells were studied in vitro and in vivo; Western blot (WB) and ELISA were used to evaluate MET and HGF expression, activation, and downstream signaling. Cell culture assays tested the impact of HGF-induced MET activation and anti-MET–specific siRNA inhibition on cell proliferation, migration, and invasion; in vivo gel-foam assays were used to evaluate angiogenesis. Cells stably transduced with anti-MET short hairpin RNA (shRNA) constructs were tested for growth and metastasis in severe combined immunodeficient (SCID) mice. The effect of the tyrosine kinase inhibitor XL184 (Exelixis) targeting MET/VEGFR2 (vascular endothelial growth factor receptor 2) on local and metastatic MPNST growth was examined in vivo. Results: All three markers were expressed in MPNST human samples; pMET expression was an independent prognosticator of poor patient outcome. Human MPNST cell lines expressed MET, HGF, and pMET. MET activation increased MPNST cell motility, invasion, angiogenesis, and induced matrix metalloproteinase-2 (MMP2) and VEGF expression; MET knockdown had inverse effects in vitro and markedly decreased local and metastatic growth in vivo. XL184 abrogated human MPNST xenograft growth and metastasis in SCID mice. Conclusions: Informative prognosticators and novel therapies are crucially needed to improve MPNST management and outcomes. We show an important role for MET in MPNST, supporting continued investigation of novel anti-MET therapies in this clinical context. Clin Cancer Res; 17(12); 3943–55. ©2011 AACR.
Quality of Life Among Younger Women With Breast Cancer
Authors: Nancy E. Avis, Sybil Crawford, Janeen Manuel
Journal: Journal of Clinical Oncology (2005)

Purpose To describe quality of life (QOL) of younger women 4 to 42 months after breast cancer diagnosis and to identify factors associated with impaired QOL. Methods A total of 202 women diagnosed with stage I to III breast cancer at age 50 or younger from 4 to 42 months after breast cancer diagnosis previously completed a mailed survey. Global QOL; health-related QOL as measured by the Functional Assessment of Cancer Therapy–Breast Cancer (FACT-B); medical history; symptoms; days of work/activity missed after diagnosis; relationship, sexual, and body image problems; coping strategies; and feelings of preparedness were measured. Results General aches and pains and unhappiness with appearance were reported by more than 70% of women. Hot flashes (P = .0007), pain with sexual intercourse (P = .02), and difficulty with bladder control (P = .002) all significantly increased with age. Global QOL was significantly lower than for a nonpatient sample of younger women (P &lt; .0001). In general, few sociodemographic and medical factors were related to QOL. In multivariate analyses, days of work/usual activity missed immediately after diagnosis; relationship, sexual, or body image problems after diagnosis; and coping strategies were related to almost all QOL domains. Ongoing treatment, vaginal dryness, and feeling unprepared for the impact of breast cancer were related to some domains. Conclusion Younger breast cancer survivors are at risk for impaired QOL up to several years after diagnosis. Younger women, especially those at high risk for lower QOL, may need interventions that specifically target their needs related to menopausal symptoms and problems with relationships, sexual functioning, and body image. Preparing younger woman for the impact of breast cancer may also prove beneficial.
Surveillance programmes for colorectal cancer in inflammatory bowel disease: have we got it right?
Authors: C. N Bernstein
Journal: Gut (2008)

While it is generally agreed that screening for colon cancer is a rational strategy in chronic colitis of ulcerative colitis or Crohn’s disease, there remains some debate over the approach to managing outcomes of dysplasia surveillance colonoscopy. While some have advocated for colectomy for low grade dysplasia,1–3 others have argued for more surveillance;4 while some have argued for polypectomy for adenoma-like masses (ALMs)5 others have shown the potential for disasterous outcomes if polypectomy is pursued where rigorous follow-up will not be sustained.6 However, there has been less discussion about the technical approach to dysplasia surveillance. In survey studies in the US and UK it was shown that surveillance colonoscopy frequency and biopsy protocols have varied widely.7 8 One study suggested that at least 33 biopsies were required to maximise dysplasia discovery,9 but this has never been revisited. To counter the problem of time and expense incurred with 30+ biopsies chromoendoscopy emerged as a means to target biopsies and otherwise minimise random multiple biopsies.10 11 In this issue of Gut , Lutgens et al ( see page 1246 ) address the very basic question of timing the initiation of dysplasia surveillance.12 Elsewhere, it has been identified that colon cancers may occur before 8 years of disease.13 14 However, in a countrywide assessment Lutgens et al have systematically attempted to discern how often cancers are missed if the starting points given in current surveillance guidelines are adhered to. In the British guidelines it is suggested that surveillance colonoscopy should be initiated at 8 years in extensive colitis and 15 years in left-sided colitis.15 The authors adequately discuss that this recommendation was based mostly on expert opinion rather than on firm data. For the most part, the 8 year starting point for extensive …