tbuckley/cabot-search huggingface dataset:
Reforming the contract of UK consultants Commentary: To increase consultants' activity should not be the main aim
Authors: A. Maynard
Journal: BMJ (2001)

# Reforming the contract of UK consultants {#article-title-2}

See Editorial by Riordan and News 

The NHS Plan expressed the intention of government to “fundamentally overhaul” the national contract for UK hospital specialists to “reward and incentivise those who do most for the NHS.”1 How can this be achieved?

#### Summary points

The contract for UK hospital consultants has been criticised by the BMA, the House of Commons Select Committee on Health, and the current government

It has failed to deliver consistent activity and accountability in both the NHS and the private sector

If the NHS Plan is to be carried out, existing variations in performance by consultants have to be better managed

A new contract could involve a basic salary supplemented by bonuses and a fee for each “item” of service

The contract would require appraisal and management of consultants' activity

Informed debate about the design of a new contract is essential, as is its evaluation once it is introduced

The current UK pay system for hospital consultants is a fixed salary with selective bonus payments (distinction awards), which were introduced early in the existence of the NHS to reward “excellence.” UK consultants with a full time NHS contract can undertake limited private practice (with remuneration no higher than 10% of their NHS salary); those with a part time contract (including the “maximum part time” contract, in which consultants receive 10/11 of a full time salary) can undertake unlimited private practice.

Contributing to the renegotiation of consultants' contracts, the House of Commons Select Committee on Health published a report aiming “to examine NHS consultants' contracts in terms of their accountability, effectiveness, and efficiency” and to examine the impact of private practice on the NHS.2 The committee expressed surprise that “the contract managing the work of these vitally important professionals remained, in essence, unchanged since the formation of the NHS …
NIH Clinical Center closes its pharmacy after contamination found
Authors: M. McCarthy
Journal: BMJ (2015)

The US National Institutes of Health (NIH) has suspended all operations of its specialized pharmacy that produces investigational drugs for clinical trials after inspectors from the Food and Drug Administration discovered “serious manufacturing problems and lack of compliance with standard operating procedures,” NIH officials said on 4 June.

The investigation was launched after two vials of albumin prepared at the Pharmaceutical Development Section at the NIH Clinical Center were found …
Genetic Determinism and Evolutionary Reconstruction of a Host Jump in a Plant Virus
Authors: Nikon Vassilakos, Vincent Simon, Aliki Tzima, Elisabeth Johansen, Benoît Moury
Journal: Molecular Biology and Evolution (2015)

In spite of their widespread occurrence, only few host jumps by plant viruses have been evidenced and the molecular bases of even fewer have been determined. A combination of three independent approaches, 1) experimental evolution followed by reverse genetics analysis, 2) positive selection analysis, and 3) locus-by-locus analysis of molecular variance (AMOVA) allowed reconstructing the Potato virus Y (PVY; genus Potyvirus, family Potyviridae) jump to pepper (Capsicum annuum), probably from other solanaceous plants. Synthetic chimeras between infectious cDNA clones of two PVY isolates with contrasted levels of adaptation to C. annuum showed that the P3 and, to a lower extent, the CI cistron played important roles in infectivity toward C. annuum. The three analytical approaches pinpointed a single nonsynonymous substitution in the P3 and P3N-PIPO cistrons that evolved several times independently and conferred adaptation to C. annuum. In addition to increasing our knowledge of host jumps in plant viruses, this study illustrates also the efficiency of locus-by-locus AMOVA and combined approaches to identify adaptive mutations in the genome of RNA viruses.
Proceedings of the British Thoracic Society, Scottish Thoracic Society and Thoracic Society of Australia. The 1987 summer meeting. 1-3 July, Edinburgh. Abstracts.
Authors: C.E. Bucknall, C. Robertson, R.D. Stevenson, F. Moran
Journal: Thorax (1987)

doubt has been cast on the safety and desirability of fibreoptic bronchoscopy in the elderly (Grant IBW, Br Med J 1986;293:286-7).To answer this question, we looked at the safety and acceptability of the procedure in 60 patients, aged 80-92 over the four year period May 1982-May 1986.Thirty-four patients were male.Sedation was with atropine, fentanyl, and diazepam, 2% lignocaine being instilled locally over the cords.There was no serious morbidity and no mortality.The diagnostic yield was similar to younger age groups.Twenty-one patients had histologically proved carcinoma of the bronchus, one a benign polyp, one tuberculosis diagnosed from washings, two collapsed lobes with re-expansion following removal of secretions.The remainder either showed infective changes or were normal.Where no tumour was seen active treatment resulted in improvement in all but four.Of those with tumour, four were treated with radiotherapy with symptomatic relief, the remainder being treated conservatively.A positive diagnosis of malignancy greatly helped the planning of future care.We conclude that fibreoptic bronchoscopy is a safe, useful procedure in this group of patients.A randomised, double blind comparison of midazolam and diazepam -(Diazemuls) as sedation for fibreoptic bronchoscopy RG TAYLOR, F JOHNSON, JCG COX, PJH POI, AG assessment of the procedure.Patients benefit subjectively, and cough less when using the sidepiece, perhaps due to biofeedback.Patients also cough less but do not benefit subjectively from simple visual distraction as provided by slides.The operator considered both measures beneficial, perhaps because of reduced coughing.705
Loss-of-function variants in ATM confer risk of gastric cancer
Authors: Hannes Helgason, Thorunn Rafnar, Halla S Olafsdottir, Jon G Jonasson, Asgeir Sigurdsson, Simon N Stacey, Adalbjorg Jonasdottir, Laufey Tryggvadottir, Kristin Alexiusdottir, Asgeir Haraldsson, Louise le Roux, Julius Gudmundsson, Hrefna Johannsdottir, Asmundur Oddsson, Arnaldur Gylfason, Olafur T Magnusson, Gisli Masson, Thorvaldur Jonsson, Halla Skuladottir, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Patrick Sulem, Kari Stefansson
Journal: Nature Genetics (2015)
PD-1/PDL-1 expression in colorectal cancer and its implications for tumor immune evasion
Authors: M. Gasser, M. Grimm, E. Nichiporuk, M. Bueter, J. Lutz, T. Lebedeva, M. Koenigshausen, A. Thiede, U. Heemann, D. Meyer, A. Waaga-Gasser
Journal: Journal of Clinical Oncology (2006)

10046 Background: Malignant tumors may evade immunological surveillance by an active downregulation of T cell activation by PD-1 (programmed death 1)/ PDL-1 signaling. This would result in a decreased immune response, thus, promoting tumor growth. Methods: We analyzed the expression of PD-1/PDL-1 genes, cytokines, and T cell subpopulations in tumor tissues of 81 consecutive patients who underwent surgery for primary colorectal cancer according to their UICC stage. Expression of PD-1/PDL-1, T cell subpopulations, and cytokines in tumor tissues were assessed using immunostaining, immunofluorescence, and Real Time PCR. Results: PDL-1 expression on tumor cells was significantly increased, whereas PD-1 expression on tumor cells was decreased at UICC stage III/IV. However, PD-1 expression on infiltrating CD4+ T cells was detectable in patients with advanced tumors whereas PDL-1 expression on CD4+ cells was particularly found at early stages. More regulatory T cells (CD4+CD25+CTLA-4+Foxp3+) were observed in tumors of stage III/IV patients compared to early stages. In addition, a remarkably increased amount of IL-10 was observed in the tumors of UICC III/IV patients. High expression of TGF-ß receptor II in tumors correlated with a progressive course of the disease and tumor relapses, i.e. TGF-ß RII in early tumor stages was indicative for early tumor progress. Conclusions: Our findings indicate that PDL-1 plays a key role during tumor progression and that regulatory T cells are involved in the process of evasion from immune surveillance. The elevated PDL-1 expression on T cells at early tumor stages suggests that PD1/PDL-1 interaction mediates inhibitory signals between T cells enabling the tumor to progress. PDL-1 blockade may prove to be a valuable approach for cancer immunotherapy. No significant financial relationships to disclose.
Family Therapy for Anorexia Nervosa in Adolescence: A Review
Authors: M Hodes, I Eisler, C Dare
Journal: Journal of the Royal Society of Medicine (1991)

Anorexia nervosa is a serious psychosomatic disorder This, in combination with dissatisfaction concerning in which the sufferer, usually female, believes she is the traditional treatments has led to the development fat despite all attempts to persuade her otherwise and of a novel approachh -:family therapy.This development in consequence tries with all her determination to lose has occurred despite the growing evidence for weight'.A rigorous diet is adopted, sometimes in constitutional and genetic -factors in the aetiology conjunction with other strategies for weight control of anorexia nervosa2O.Family members form the such as the use of laxatives, self-induced vomiting or context in which individual development occurs.excessive exercising.This regimen, in addition to Because of their interdependence, the psychological emaciation, leads to amenorrhoea in women or the evolution of each family nember is closely-entwined equivalent endocrine disturbance in men, ie a loss of with the development of the family as a unit.libido.Severe metabolic disturbances such as hypo-This is manifested by -the members' behaviour kalaemia, bradycardia, aniypotension are eventually and communications beingboth influences upon and
Population pharmacokinetics and pharmacodynamics of GSK961081 (MABA) in patients with moderate to severe COPD
Authors: Claire Ambery, Pascal Wielders, Andrea Ludwig-Sengpiel, Robert Chan, John Riley
Journal: European Respiratory Journal (2013)

The aim of this study was to characterise population pharmacokinetics (PK) and pharmacodynamics (PD) of GSK961081 (MABA), a bi-functional molecule with muscarinic antagonist (MA) and beta 2  agonist (BA) properties.  Nonlinear mixed effects modelling of plasma GSK961081 concentration-time data (Day28) and dose response of AM trough FEV 1  data (Day29) conducted using NONMEM. Data obtained from MAB115032 (Wielders et al.  EurRespirJ  2012;40:Suppl.56,3081); a 4-week investigation of once and twice daily inhaled GSK961081. Simulations used to assess model predictive performance.  The PK parameters for 2-compartment model determined with good precision (relative standard error (RSE -1  (0.313,0.535). No covariates were included in the PK model. The PD parameters for a maximum effect (Emax) dose response model were determined with reasonable precision (RSE 1  included as covariate in PD model; no other covariates including dosing frequency included based on statistical testing. Model adequacy demonstrated by good predictive performance.  The models described can be used as tools for guiding GSK961081 clinical development. There was no influence of dosing regimen on the PD model, suggesting once or twice daily dosing could be used.
Study showing the efficacy of aromasin in metastatic CA breast in postmenopausal women
Authors: K. S. Velu
Journal: Journal of Clinical Oncology (2008)

12023 Background: Aromatase inhibitors have been shown to be better choice for Hormone therapy in Post menopausal receptor positive woman when compared to Tamoxifen. Methods: 22 patients with stage IIIB (4pts) & stage IV (18pts) who have failed on chemotherapy/tamoxifen or not fit for any modality of treatment were included in the study. 21 were postmenopausal & one patient was post hysterectomy status.21 patients had ER/PR receptor positive status while 1patient ER/PR status was not known.9 patients had under gone MRM, 10 patients had received CT prior to aromasin while 4 patients received CT along with Tamoxifen therapy. All patients were started on Aromasin and patients who were previously on Tamoxifen were switched over to Aromasin Results: All patients were observed on Aromasin. Period of remission ranged between 1–4 yrs. Complete response was seen in 5 patients (22.7%). Stable disease was noted in 8 patients (36.3%) and progressive disease was noted in 9 patients (40.9%). Responders had improved to such an extent that they were able to withstand palliative surgical procedure. No incidence of thromboembolic event or endometrial carcinoma was reported in the study population. Conclusion: In our study we found Aromasin to be very safe and effective mode of Hormone therapy in advanced CA-Breast in post menopausal woman with positive receptor status. No significant financial relationships to disclose.
Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine.
Authors: S B Murphy, W P Bowman, M Abromowitch, J Mirro, J Ochs, G Rivera, C H Pui, D Fairclough, C W Berard
Journal: Journal of Clinical Oncology (1986)

To address the problem of historically poor results in the treatment of children with advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia (ALL), an intensive chemotherapy regimen was devised using the most effective single agents in high-dose short courses. Treatment commenced with a fractionated schedule of intravenous (IV) cyclophosphamide (300 mg/m2 every 12 hours for six doses) followed immediately by Adriamycin (50 mg/m2) and vincristine (1.5 mg/m2) with combined intrathecal (IT) methotrexate and cytarabine. Predictably, this treatment produced virtually complete disappearance of all tumor and profound myelosuppression. Immediately on hematologic recovery, IV high-dose methotrexate (1,000 mg/m2 over 24 hours) followed by IV cytarabine (400 mg/m2 over the next 48 hours) was administered with leucovorin rescue and repeated IT treatments. The treatment sequence described above is repeated four times, with the dose of cytarabine doubled in succeeding courses, up to 3,200 mg/m2. The entire planned therapy required approximately 24 weeks. Since 1981, we treated a total of 29 children with this approach, 19 of whom had massive unresectable intraabdominal tumor. According to initial extent of disease, 17 were classified as stage III, four as stage IV non-Hodgkin's lymphoma (NHL), and eight as B cell ALL. Eight of the 12 patients with stage IV NHL or B cell ALL had initial involvement of the CNS. Twenty-seven of 29 patients (93%) attained a complete remission. Fourteen of 17 stage III NHL patients remain disease free, for periods ranging from 3+ months to 4 1/2+ years. The actuarial estimate of the proportion of stage III patients remaining disease free at 2 years is 81%. Results in patients with initial involvement of the CNS and/or marrow are much less favorable, with only two of ten patients who attained remission apparently being cured. In addition to stage, the initial serum lactic dehydrogenase (LDH) level emerged as a prognostic indicator, higher levels (over 1,000 IU/L) being associated with the worst prognosis (P less than .05). Major toxicity consisted of severe hematopoietic suppression and febrile episodes associated with neutropenia. We conclude that this treatment is highly effective for advanced-stage Burkitt's tumors in children free of initial CNS involvement.
Assessment of German national lung cancer guideline quality indicators in routine practice – Does the new TNM-system make a difference?
Authors: Torsten Blum, Jens Kollmeier, Nicolas Schönfeld, Wim Ammenwerth, Sandra Delis, Wolfram Grüning, Wiebke Nehls, Torsten T. Bauer
Journal: European Respiratory Journal (2011)

Background:  Quality assurance is an essential tool for assessing and optimizing quality of care. For that purpose, the German national lung cancer guideline (GL), published in 2010, has defined nine quality indicators (QI). So far, neither these QI have been prospectively evaluated, nor corresponding reference intervals have been specified. Furthermore, no evidence exists for the practicability of the QI concerning the utilization of the new TNM-system (UICC 7).   Methods:  All patients with a first diagnosis of lung cancer (FD), admitted to our lung cancer centre between 01.01.2008 and 31.12.2009, were included into this study. Data collection has been performed prospectively using our tumour documentation system (TDS) and hospital information system (HIS). In a retrospective analysis two groups were defined in which the patients were staged by the old UICC 6 (FD in 2008) and the new UICC 7 (FD in 2009) staging system, respectively.   Results:  Patients9 characteristics were similar in both groups (2008: 595 pt.; 2009: 641 pt.). For 7 out of 9 QI a result could be determined according to the defaults of the GL (example: tab.1)   Conclusions:  In this study we were able to completely assess 7 out of 9 QI proposed by the GL exclusively on the basis of routine data of our TDS and KIS. These data will not only help to improve the quality of care in our lung cancer centre but also allow first conclusions on the undetermined reference intervals of the GL-QI. However, the GL-QI should be further evaluated within a prospective, multicentric study.
PGD2 biosynthesis in several human mast cell models is catalyzed by cycloxygenase-1
Authors: Jeong-Hee Choi, Sven-Erik Dahlén, Gunnar Nilsson
Journal: European Respiratory Journal (2011)

Background:  Mast cells and eicosanoid mediators play an important role in asthma. There are few studies comparing eicosanoid release from different human mast cell models.   Objective:  We characterized release of eicosanoids from the LAD2 human mast cell line and primary cultured-human mast cells from cord blood (CBMC) and peripheral blood (PBMC).   Methods:  Mast cells were stimulated with anti-human IgE via cross-linking of IgE antibodies for 30 minutes, and β-hexosaminidase, cysteinyl leukotrienes (CysLTs), LTB 4 , prostaglandin D 2  (PGD 2 ) were measured, and expression of cyclooxygenase (COX)-1 and COX-2 were studied by western blot.   Results:  LAD2 released β-hexosaminidase and PGD 2  after stimulation with anti-human IgE in a dose-dependent manner, but not CysLTs or LTB 4 . CBMC and PBMC showed significant increase of cysLTs and LTB 4  in addition to β-hexosaminidase and PGD 2  after stimulation. IL-4 priming did not enhance CysLTs release in any of the mast cell models. IL-4 primed LAD2 however showed significant enhancement of PGD 2  release. The PGD 2  release from the three human mast cell models was consistently abolished by the selective COX-1 inhibitor, FR122047 (p 2  release after treatment with COX-1 siRNA.   Conclusion:  LAD2 is a good model for studies of PGD 2  release, but not for CysLTs. The PGD 2  release from the isolated human mast cells is dependent on COX-1, in line with recent  in vivo  findings in asthmatics (Daham K et al. Clin Exp Allergy 2011;41:36-45)  This abstract was supported by ERS/Marie Curie joint research fellowship (MC 1549-2010).
Using CellMiner 1.6 for Systems Pharmacology and Genomic Analysis of the NCI-60
Authors: William C. Reinhold, Margot Sunshine, Sudhir Varma, James H. Doroshow, Yves Pommier
Journal: Clinical Cancer Research (2015)

Abstract The NCI-60 cancer cell line panel provides a premier model for data integration, and systems pharmacology being the largest publicly available database of anticancer drug activity, genomic, molecular, and phenotypic data. It comprises gene expression (25,722 transcripts), microRNAs (360 miRNAs), whole-genome DNA copy number (23,413 genes), whole-exome sequencing (variants for 16,568 genes), protein levels (94 genes), and cytotoxic activity (20,861 compounds). Included are 158 FDA-approved drugs and 79 that are in clinical trials. To improve data accessibility to bioinformaticists and non-bioinformaticists alike, we have developed the CellMiner web–based tools. Here, we describe the newest CellMiner version, including integration of novel databases and tools associated with whole-exome sequencing and protein expression, and review the tools. Included are (i) “Cell line signature” for DNA, RNA, protein, and drugs; (ii) “Cross correlations” for up to 150 input genes, microRNAs, and compounds in a single query; (iii) “Pattern comparison” to identify connections among drugs, gene expression, genomic variants, microRNA, and protein expressions; (iv) “Genetic variation versus drug visualization” to identify potential new drug:gene DNA variant relationships; and (v) “Genetic variant summation” designed to provide a synopsis of mutational burden on any pathway or gene group for up to 150 genes. Together, these tools allow users to flexibly query the NCI-60 data for potential relationships between genomic, molecular, and pharmacologic parameters in a manner specific to the user's area of expertise. Examples for both gain- (RAS) and loss-of-function (PTEN) alterations are provided. Clin Cancer Res; 21(17); 3841–52. ©2015 AACR.
Symptoms and Neurocognition as Rate Limiters in Skills Training for Psychotic Patients
Authors: Thomas E. Smith, James W. Hull, Susan Romanelli, Eric Fertuck, Kim A. Weiss
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This study aimed to replicate findings that neurocognitive capacity in schizophrenia is more predictive of acquisition of social skills than are symptoms. METHOD: Thirty-two hospitalized patients with chronic psychotic disorders were randomly assigned to community reintegration skills training or supportive group therapy. Neurocognitive functioning was assessed before treatment, and symptoms and skill levels were measured before and after treatment. RESULTS: The skills training group showed significantly greater skill acquisition. In a regression model, skill acquisition was predicted by group membership and verbal memory capacity and not by symptoms. CONCLUSIONS: With methodological advances, the authors replicated findings regarding the importance of neurocognition in determining treatment outcome in schizophrenia.
Analysis of serum prohepcidin and hepcidin levels in COPD patients by stages and by patient cathegory
Authors: Damian Korzybski, Adam Nowinski, Beata Broniarek-Samson, Dorota Gorecka
Journal: European Respiratory Journal (2013)

Introduction:Hepcidin is a hormone produced in the liver and responsible for the iron homeostasis. By inhibiting ferroportin, hepcidin inhibits the transport of irons from enterocytes, thus reducing the absorption of iron. Hepcidin is one of acute phase proteins and correlate with inflammation.  Aims:The aim of the study was to evaluate the relationships between severity of COPD and serum hepcidin and prohepcidin levels.  Methods:COPD patients treated in respiratory department were studied. Levels of hepcidin, prohepcidin, Hb and Fe were assessed.  Results:61 COPD patients were analyzed (24 F, 37 M). Results are shown in the table, they are means ±SD. There was correlation: prohepcidin and hepcidin (r=0,44), Hb and PaO2 (r=-0,51), Fe and Hb (r=0,34).  Conclusions:There was no significant differences in hepcidin and prohepcidin serum levels in COPD stages and cathegories. There was significant differences in oxygen partial pressure.