tbuckley/cabot-search huggingface dataset:
The role of soluble TGF-beta and its dynamics for predicting the prognosis in unresectable pancreatic cancer patients treated with chemotherapy.
Authors: Hyunkyung Park, Ju-Hee Bang, Ah-Rong Nam, Ji Eun Park, Mei Hua Kim, Yung-Jue Bang, Do-Youn Oh
Journal: Journal of Clinical Oncology (2018)

288 Background: Transforming growth factor-beta (TGF-β) is a multifunctional regulatory factor. Here, we measured serum soluble TGF-β (sTGF-β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. Methods: Sixty patients treated with FOLFIRINOX as the first-line palliative chemotherapy were prospectively enrolled. We prospectively collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF-β using an enzyme-linked immunosorbent assay. Results: The patients’ median overall survival (OS) and progression free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5–12.1) and 6.5 (95% CI, 4.9–8.1) months, respectively. Patients with low sTGF-β at diagnosis ( &lt; 31.2ng/mL) had better OS and PFS than patients with high sTGF-β, respectively (OS, 13.7 vs. 9.2 months; hazard ratio [HR], 2.602; P =0.004; PFS, 9.0 vs. 5.8 months; HR, 2.010; P =0.034). At the time of disease progression, sTGF-β was increased compared with that of diagnosis (mean 26.4 vs. 23.9ng/mL). Especially, in patients with a partial response, sTGF-β was significantly increased at disease progression (mean 25.7 vs. 31.0ng/mL; P =0.049). Conclusions: Pre-treatment sTGF-β levels serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. Likewise, the dynamics of sTGF-β during chemotherapy have prognostic value.
Translation of Knowledge to Practice—Improving Awareness in NSCLC Molecular Testing
Authors: Alona Zer, Jean Claude Cutz, Harman Sekhon, David M. Hwang, Christina Sit, Manjula Maganti, Mike Sung, Matthew Binnie, Anthony Brade, Tae Bong Chung, Suzanne Kamel-Reid, Narinder Paul, Ming S. Tsao, Tom Waddell, Gilda da Cunha Santos, Milan Patel, Ron F. Carter, Natasha B. Leighl
Journal: Journal of Thoracic Oncology (2018)
Postgraduate Diploma/Master of Science in Wound Healing and Tissue Repair
Authors: David Sainsbury
Journal: BMJ (2007)

FURTHER INFORMATION 

Department of Wound Healing, School of Medicine, Cardiff University, Heath Park Campus, Cardiff CF14 4XN. admin@whru.co.ukwww.whru.co.uk

For doctors, nurses, and allied health professionals with an interest in wound healing and tissue repair. It is suitable for senior house officers and registrars in plastic surgery, general surgery, and vascular surgery. Other course members included tissue viability nurses, primary care nurses, pharmacists, and podiatrists.

Most medics do the course after completing their postgraduate exams. It is ideal after finishing a basic surgical rotation before getting on to a higher surgical post, but it is …
Scottish GPs resign from BMA in protest at new contract
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A group of GPs in Scotland are resigning from the BMA in protest at the agreement of a new contract that they claim will have a “devastating” effect on patients in rural areas.

Although the contract was accepted by a majority of GPs in Scotland who took part in a BMA ballot,1 28% rejected it, with the strongest opposition coming from doctors in rural and deprived areas, on the grounds that the reworked funding formula shifts money to urban practices with elderly patients.

After the ballot the BMA responded to the criticisms by establishing a working group to ensure that the contract was delivered in a way that worked for rural areas.

But in an open letter to BMA leaders (see “Related Content”), 10 GPs from rural and urban parts …
THE IMPACT OF CIGARETTE SMOKING FOR HIGH-RISK CORONARY PLAQUE DEVELOPMENT AND PLAQUE PROGRESSION BY SERIAL CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Hyung-Bok Park, Sang-Eun Lee, Byoung Kwon Lee, Martin Hadamitzky, Yong-Jin Kim, Edoardo Conte, Daniele Andreini, Gianluca Pontone, Matthew Budoff, Ilan Gottlieb, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo Marques, Jonathon Leipsic, Jung Hyun Choi, Renu Virmani, Habib Samady, Peter Stone, Daniel Berman, Jagat Narula, Leslee Shaw, Jeroen Bax, James K. Min, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)
Towards the identification of the mechanism of action of antitumor 1-methyl-D-tryptophan
Authors: M.T. Pallotta, A. Iacono, E. Albini, C. Orabona, M.L. Belladonna, R. Bianchi, A. Coletti, F. Greco, A. Macchiarulo, U. Grohmann
Journal: Annals of Oncology (2018)
Response by Kosiborod et al to Letters Regarding Article, “Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)”
Authors: Mikhail Kosiborod, Matthew A. Cavender, Alex Z. Fu, John P. Wilding, Kamlesh Khunti, Reinhard W. Holl, Anna Norhammar, Kåre I. Birkeland, Marit Eika Jørgensen, Marcus Thuresson, Niki Arya, Johan Bodegård, Niklas Hammar, Peter Fenici
Journal: Circulation (2018)
Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome
Authors: Martina Gaggl, Christof Aigner, Dorottya Csuka, Ágnes Szilágyi, Zoltán Prohászka, Renate Kain, Natalja Haninger, Maarten Knechtelsdorfer, Raute Sunder-Plassmann, Gere Sunder-Plassmann, Alice Schmidt
Journal: Journal of the American Society of Nephrology (2017)

Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1–4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.
Shifts in Selective Pressures on Snake Phototransduction Genes Associated with Photoreceptor Transmutation and Dim-Light Ancestry
Authors: Ryan K Schott, Alexander Van Nynatten, Daren C Card, Todd A Castoe, Belinda S W Chang
Journal: Molecular Biology and Evolution (2018)

The visual systems of snakes are heavily modified relative to other squamates, a condition often thought to reflect their fossorial origins. Further modifications are seen in caenophidian snakes, where evolutionary transitions between rod and cone photoreceptors, termed photoreceptor transmutations, have occurred in many lineages. Little previous work, however, has focused on the molecular evolutionary underpinnings of these morphological changes. To address this, we sequenced seven snake eye transcriptomes and utilized new whole-genome and targeted capture sequencing data. We used these data to analyze gene loss and shifts in selection pressures in phototransduction genes that may be associated with snake evolutionary origins and photoreceptor transmutation. We identified the surprising loss of rhodopsin kinase (GRK1), despite a low degree of gene loss overall and a lack of relaxed selection early during snake evolution. These results provide some of the first evolutionary genomic corroboration for a dim-light ancestor that lacks strong fossorial adaptations. Our results also indicate that snakes with photoreceptor transmutation experienced significantly different selection pressures from other reptiles. Significant positive selection was found primarily in cone-specific genes, but not rod-specific genes, contrary to our expectations. These results reveal potential molecular adaptations associated with photoreceptor transmutation and also highlight unappreciated functional differences between rod- and cone-specific phototransduction proteins. This intriguing example of snake visual system evolution illustrates how the underlying molecular components of a complex system can be reshaped in response to changing selection pressures.
The president of the Association of Directors of Public Health
Authors: Rubinder K Bains, Irfan Ghani, Mary Thompson
Journal: BMJ (2008)

I’ve always found epidemiology fascinating. Its basic appeal to me comes from an aptitude with numbers, which I inherited from my father, a maths teacher. I first became hooked while a medical student at Barts in the 1980s. We had an inspiring lecturer, Professor Nicholas Wald, now Sir Nicholas Wald. He invented the Triple Test, used to detect the risk of Down’s syndrome in pregnancy.1 After I completed house jobs in 1989, I worked back at Barts as a senior house officer in epidemiology, which I loved. Coming from the hierarchical system in hospitals, I found myself able to touch the boundaries of human knowledge within a few months. I then did further senior house officer posts in oncology and gynaecology. In 1992 I joined the public health training scheme as a lecturer in public health at King’s College, London. After completing training, I …
Abstract 10209: The Severity of the Metabolic Syndrome Increases over Time within Individuals, Independent of Baseline Metabolic Syndrome Status and Medication Use: The Atherosclerosis Risk in Communities Study
Authors: Abhishek Vishnu, Matthew J Gurka, Mark D DeBoer
Journal: Circulation (2015)

Background: Clinical significance of traditional ATP-III metabolic syndrome (MetS) is a subject of debate, possibly due to its inability to track disease progression over time. We have developed a continuous MetS severity z-score such that the relative contributions of each of the MetS components to the overall severity score vary by sex- and race/ethnicity, and thus the score changes over time with MetS components. We aim to examine how MetS severity changes over time within individuals. Methods: Changes in MetS severity score were assessed over a 12-year period (Visits 1-4) among 9,291 participants of the Atherosclerosis Risk in Communities study, after excluding those with baseline MetS, CVD or diabetes. Age-adjusted rate of change in the MetS severity score and MetS prevalence as assessed using ATP-III MetS criteria were compared among sex- and racial/ethnic subgroups. Further, effects of age (&lt;50, 50-60, and &gt;60 years) and use of medications for hypertension, diabetes and dyslipidemia on MetS severity progression were examined. Results: MetS severity z-scores increased among 76% of participants between visits 1 and 4, with an overall increase in z-score from 0.08 (±0.77) at baseline to 0.48 (±0.96) at visit 4. The greatest progression was observed among African-American women. Baseline MetS severity z-scores predicted the time until ATP-III MetS diagnosis, with 90.2% of individuals with score of ≥1.0 (n=1,097) progressing to ATP-III MetS by visit 4. Score progression was higher among those younger (&lt;50 years) at baseline but was independent of baseline MetS status or the use of medications to treat blood pressure, lipids and diabetes. Conclusion: The severity of metabolic derangements as measured using this sex- and race/ethnicity specific MetS z-score increases over time within individuals and predicts diagnosis of ATP-III MetS. These data may have implications for tracking MetS related risk over time within individuals.
More than 400 doctors to be trained for overseas emergencies
Authors: Tom Moberly
Journal: BMJ (2012)

More than 400 doctors will be trained over the next year to assist in overseas emergencies, the government has announced.

Training to help provide treatment after tsunamis, earthquakes, and floods will be provided for doctors who pre-register with the UK’s International Emergency Trauma Register (UKIETR). The register works to coordinate the deployment of volunteers to rapid onset disasters. It was set up to enable the UK to provide timely and coordinated …
Corrigendum: Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine (Nature Genetics, (2016), 10.1038/ng.3598)
Authors: P Gormley, V Anttila, B S Winsvold, P Palta, T Esko, T H Pers, K H Farh, E Cuenca-Leon, M Muona, N A Furlotte, T Kurth, A Ingason, G McMahon, L Ligthart, G M Terwindt, M Kallela, T M Freilinger, C Ran, S G Gordon, A H Stam, S Steinberg, G Borck, M Koiranen, L Quaye, Adams Hhh., T Lehtimäki, A P Sarin, J Wedenoja, D A Hinds, J E Buring, M Schürks, P M Ridker, M Gudlaug Hrafnsdottir, H Stefansson, S M Ring, J J Hottenga, Penninx Bwjh., M Färkkilä, V Artto, M Kaunisto, S Vepsäläinen, R Malik, A C Heath, Madden Paf., N G Martin, G W Montgomery, M I Kurki, M Kals, R Mägi, K Pärn, E Hämäläinen, H Huang, A E Byrnes, L Franke, J Huang, E Stergiakouli, P H Lee, C Sandor, C Webber, Z Cader, B Muller-Myhsok, S Schreiber, T Meitinger, J G Eriksson, V Salomaa, K Heikkilä, E Loehrer, A G Uitterlinden, A Hofman, C M van Duijn, L Cherkas, L M Pedersen, A Stubhaug, C S Nielsen, M Männikkö, E Mihailov, L Milani, H Göbel, A L Esserlind, A Francke Christensen, T Folkmann Hansen, T Werge, J Kaprio, A J Aromaa, O Raitakari, M Arfan Ikram, T Spector, M R Järvelin, A Metspalu, C Kubisch, D P Strachan, Ferrari, A C Belin, M Dichgans, M Wessman, van den Maagdenberg Amjm., J A Zwart, D I Boomsma, G Davey Smith, K Stefansson
Journal: Nature Genetics (2016)
Abstract P3-05-15: PD-1 expression and its correlation with tumour infiltrating lymphocytes and Ki67 in patients with breast cancer
Authors: H Vos, K Lambein, G Floris, I Nevelsteen, A Smeets
Journal: Cancer Research (2018)

Abstract Introduction: Immunotherapy targeting the programmed death-1 (PD-1) checkpoint has resulted in good outcomes in patients with melanoma, non-small cell lung cancer and head and neck cancer. Recent data have showed that patients with ER/PR negative breast cancer might benefit from immunotherapy as well. We investigated PD-1 expression on tumour infiltrating lymphocytes (TILs), the presence of TILs and Ki67. Furthermore, the association of PD-1, TILs and Ki67 with time to metastasis was statistically determined. Methods: Resection specimens of 284 patients with an ER/PR negative invasive ductal adenocarcinoma of at least 2 cm were analysed. Haematoxylin-eosin staining was performed to determine the percentage of TILs. Subsequently these percentages were divided into three groups: less than 10%, 10%-30% and more than 30% which matches with respectively 30%, 50% and 20% of the patients. PD-1 expression on the TILs of 116 patients and Ki67 expression of 185 patients were assessed using immunohistochemistry. Results: An increase in the fraction of TILs was significantly associated with a lower risk of metastasis (hazard ratio [HR] = 0.7, 95% CI = 0.6-0.9). PD-1 expression on TILs was observed in 97% of the patients. Three patients had no expression of PD-1, this lack of PD-1 expression significantly increased the risk of metastasis (HR = 5.541, 95% CI = 1.2-25.0). No association could be noted between PD-1 expression and the amount of TILs or Ki67 (p-values of respectively 0.272 and 0.637). Similarly, no association could be noted between Ki67 and the amount of TILs (p-value = 0.1954) Conclusion: PD-1 was expressed on TILs in patients with breast cancer. Surprisingly, no correlation was found between PD-1 expression and TILs or Ki67. However, an increased amount of TILs was significantly associated with a lower risk of metastasis. Citation Format: Vos H, Lambein K, Floris G, Nevelsteen I, Smeets A. PD-1 expression and its correlation with tumour infiltrating lymphocytes and Ki67 in patients with breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-15.
Two thirds of newly appointed consultants in Scotland are employed on 9:1 contracts
Authors: Helen Jaques
Journal: BMJ (2012)

Nearly two thirds of consultants appointed in Scotland in the past year were employed on contracts with only one supporting professional activity (SPA) a week to nine direct clinical care programmed activities, an approach that the BMA says is “hamstringing” the most senior staff in the NHS.

A total of 63% (147 of 235) of the consultants appointed between December 2010 and December 2011 at the 12 health boards in Scotland that responded to a freedom of information request were on 9:1 contracts. Three boards only employed consultants on 9:1 contracts.

Nearly half (44%) of those appointed on a 9:1 contract were newly qualified consultants who had received their certificate of …
Dasatinib in Pediatric Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial
Authors: Lia Gore, Pamela R. Kearns, Maria Lucia de Martino, None Lee, Carmino Antonio De Souza, Yves Bertrand, Nobuko Hijiya, Linda C. Stork, Nack-Gyun Chung, Rocio Cardenas Cardos, Tapan Saikia, Franca Fagioli, Jong Jin Seo, Judith Landman-Parker, Donna Lancaster, Andrew E. Place, Karen R. Rabin, Mariana Sacchi, Rene Swanink, C. Michel Zwaan
Journal: Journal of Clinical Oncology (2018)

Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients &lt; 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response &gt; 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) &gt; 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response &gt; 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR &gt; 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.
I am trying to get some information on general practitioner training in Jersey, Channel Islands. Do you know if there is a vocational training scheme course running there and have you got any information on it?
Authors: Bill Irish
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Myocardial Infarction After Vascular Surgery—Reply
Authors: Yen-Yi Juo, Boback Ziaeian, Peyman Benharash
Journal: JAMA Surgery (2018)

In Reply We read with great interest the letter by Polok et al regarding our article1 and appreciate their insightful comments, which highlight several challenges in the use of retrospective databases for quality monitoring. However, several key factors deserve further consideration.
SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EFFECTS OF LOW SODIUM SALT SUBSTITUTES ON CARDIOVASCULAR OUTCOMES
Authors: Adrian V. Hernandez, Erin E. Emonds, Brett A. Chen, José Alfredo Zavala Loayza, Vinay Pasupuleti, Yuani M. Roman-Morillo, Antonio Bernabe-Ortiz, J. Jaime Miranda
Journal: Journal of the American College of Cardiology (2018)
Esthetic treatment of altered passive eruption
Authors: Monica Mele, Pietro Felice, Praveen Sharma, Claudio Mazzotti, Pietro Bellone, Giovanni Zucchelli
Journal: Periodontology 2000 (2018)

Abstract Altered passive eruption is described as a condition in which the relationship between teeth, alveolar bone and soft tissues creates an excessive display of gingiva, commonly known as a ‘gummy smile’. While there are authors who consider altered passive eruption to be a risk to periodontal health, its impact is greatest in terms of oral esthetics. The aim of periodontal management in such cases is not only to improve patient esthetics but also to restore periodontal health by re‐establishing the normal relationship between the gingival margin, alveolar bone crest and cemento–enamel junction. The aim of this article is to present a narrative review of the etiology, classification and management of altered passive eruption.
Medical schools get targets to boost intake of applicants from disadvantaged backgrounds
Authors: Caroline White
Journal: BMJ (2014)

Medical schools have been set 10 year targets to increase their quota of students from disadvantaged areas.

The targets focus on two fifths of UK postcodes and are designed to boost the intake of applicants from the areas most under-represented in higher education. The Medical Schools Council’s Selecting for Excellence Executive Group wants medical schools to increase their intake from the bottom two quintiles in the Participation of Local Regions (POLAR) data respectively from 5% to 8% and from 9% to 12% between 2013 and 2023.

The target is one of a raft of recommendations aimed at the bodies involved in the education, training, and regulation of medical students and doctors, as well as the government. The recommendations are set out in the group’s latest and final report.1

The group was set up last March to look at ways …
HEMODYNAMIC EFFECTS OF LEVOSIMENDAN IN PATIENTS WITH REACTIVE PULMONARY HYPERTENSION
Authors: Mariateresa Pucci, Paolo Severino, Maria Alfarano, Simone Calcagno, Andrea Ceccacci, Nicolo’ Salvi, Paola Scarparo, Massimo Mancone, Francesco Fedele
Journal: Journal of the American College of Cardiology (2018)