tbuckley/cabot-search huggingface dataset:
I am applying for a GP vocational training scheme. It is my understanding that most schemes take three years to complete. Is it possible to take a break in the three years to have a baby?
Authors: Bill Irish
Journal: BMJ (2005)

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>
Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma
Authors: Xin Li, Yasong Cheng, Mingzhi Zhang, Jiaqin Yan, Ling Li, Xiaorui Fu, Xudong Zhang, Yu Chang, Zhenchang Sun, Hui Yu, Lei Zhang, Xinhua Wang, Jingjing Wu, Zhaoming Li, Feifei Nan, Li Tian, Wencai Li, Ken H. Young
Journal: Journal of Hematology & Oncology (2018)

Natural killer/T-cell lymphoma (NKTCL) is a rare subtype of non-Hodgkin lymphoma that is associated with a poor outcome. Currently, the treatment needs of NKTCL remain unmet, and efforts to further improve treatment are urgently needed. Herein, seven patients with NKTCL who failed to respond to various types of chemotherapies were treated with the anti-programmed death 1 (anti-PD-1) antibody pembrolizumab at 100 mg every 3 weeks. After a median of four cycles of treatment (range 2–18), four out of seven patients responded (two complete response, two partial response, overall response rate 57%). Expression of PD1-ligand available was 50, 20, 30, 70, and 30% of five patients respectively. It is negative in one patient and not tested in one patient. Adverse events, which mostly ranged from grade I to grade III, were tolerable and could be safely handled, although immune-related pneumonitis was notable. Overall, PD-1 blockade with pembrolizumab represents a favorable strategy for the treatment of refractory/relapsed NKTCL.
Only half of salaried GPs are on model contracts
Authors: Caroline White
Journal: BMJ (2012)

A survey last month has indicated that salaried GPs in Leeds seem to be getting something of a raw contractual deal, particularly women.

Although 39 of the 40 salaried GPs who took part in the survey—a third of the 125 who were contacted—had a written contract with their practice, only 21 (53%) had contracts that were comparable with the BMA model contract.

Women, in particular, …
Asthma Does Not Explain A Decline In Post Bronchodilator Lung Function In Early Adult Life
Authors: Ramesh Jagath Kurukulaaratchy, Claire Hodgekiss, John W. Holloway, Graham Roberts, Wilfried Karmaus, Hongmei Zhang, Susan Ewart, Linda S. Mansfield, Syed H. Arshad
Journal: Journal of Allergy and Clinical Immunology (2018)
T-CELL RECEPTOR EXCISION CIRCLES: A NOVEL APPROACH TO IDENTIFY IMMUNODEFICIENCY IN NEWBORNS WITH CONGENITAL HEART DISEASE
Authors: Brooke Davey, Robert Elder, Olga Salazar, Adrienne Manning, Nicholas Bennett, Ji Hyun Lee, Nancy Cross, Tam Doan, Megan Griffiths, Neha Ahluwalia, Maria Perez, Rosa Rodrigues, Robyn Bernstein, Louis Rigos, Michelle Cloutier
Journal: Journal of the American College of Cardiology (2018)
Endoscopic transchoroidal approach to pineal region tumour with splitting of the massa intermedia
Authors: Charlotte Burford, Nida Kalyal, Viviana Minichini, Jose Lavrador, Ahilan Kailaya-vasan, Bassel Zebian
Journal: Neuro-Oncology (2018)

Combined endoscopic third ventriculostomy (ETV) and tumour biopsy is a common approach to the management of patients presenting with hydrocephalus secondary to a pineal region lesion. We report our experience in performing an ETV and limited debulking of a pineal tumour using a rigid scope through a single burr hole. This was made possible by splitting the choroid fissure (CF) and massa intermedia (MI). We also report our review of the literature of current endoscopic approaches to the biopsy of pineal region lesions combined with ETV. A 13-year-old boy presented with a two-day history of rapidly progressive headache with blurred vision, diplopia and vomiting. Brain MRI revealed a pineal region lesion associated with obstructive hydrocephalus. An endoscopic transchoroidal approach with splitting of the MI combined with an ETV was performed. This allowed successful management of the obstructive hydrocephalus and a limited debulking of the pineal tumour. The histopathologic examination revealed an immature teratoma. Post-operatively the patient made an uneventful recovery and started chemotherapy. The endoscopic transchoroidal approach with splitting of the massa intermedia, when possible, allows management of the hydrocephalus and biopsy/debulking of pineal tumours through a single burr hole even when a solid scope is used. With experience and improved instrumentation, complete endoscopic resection of pineal tumours may become common-place in the future.
A phase Ib/II trial of indomethacin and enzalutamide to treat castration-resistant prostate cancer (CRPC).
Authors: Chong-xian Pan, Primo Lara, Christopher P. Evans, Mamta Parikh, Ralph de Vere White, Marc Dall'era, Chengfei Liu, Daniel Robles, Allen Gao
Journal: Journal of Clinical Oncology (2018)

TPS394 Background: Enzalutamide (Enza) and abiraterone (Abi) are commonly used to treat CRPC. Resistance is the most common cause of treatment failure. We discovered that a critical steroidogenic enzyme AKR1C3 was significantly elevated and contributed to intratumoral androgen synthesis in Enza-resistant prostate cancer cells and tumors. Overexpression of AKR1C3 induced androgen receptor variant 7 (AR-V7) expression, while inhibition of AKR1C3 downregulated AR-V7. We then discovered that indomethacin (Indo) inhibited AKR1C3 activation and sensitized resistant CRPC cells to Enza and Abi. One patient accidentally took Indo and achieved biochemical as well as radiological response of his prostate cancer. These findings prompted us to design a clinical trial to test the combination of Indo with Enza for the treatment of CRPC and to study the underlying mechanisms of action and resistance. Methods: This investigator-initiated single-arm Phase Ib/II trial enrolls patients with progressive CRPC after Abi, adequate vital organ function, ECOG performance status 0-2, and serum testosterone &lt; 50 ng/dl. Major exclusion criteria include prior Enza treatment, brain metastasis and history of seizure. In the Phase Ib cohort, patients receive Enza 160 mg po qd and Indo 50 mg po tid to determine toxicity. The Phase II expansion will enroll 26 patients with 21 evaluable patients. This sample size provides 90% power to detect, at the 0.05 level (1-sided), the difference between a PSA response rate of 50% expected with the study treatment and a historical control of 20% with Enza alone. Co-primary endpoints are safety and PSA response of ≥50% decrease. Secondary endpoints include overall response rate as determined by the Prostate Cancer Working Group 2 criteria (PCWG2), progression-free survival and overall survival. Molecular correlative studies are exploratory endpoints. Serum and intratumoral androgen levels, full-length AR, AR-V7 and AKR1C3 will be measured to assess the effect of the combination therapy. To date, 4 patients have been enrolled to the trial (clinicaltrials.gov Identifier No: NCT02935205; this trial is funded by DoD Prostate Cancer Research Program IMPACT award). Clinical trial information: NCT02935205.
Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma
Authors: Matthew C. Altman, Elizabeth Whalen, Alkis Togias, George T. O'Connor, Leonard B. Bacharier, Gordon R. Bloomberg, Meyer Kattan, Robert A. Wood, Scott Presnell, Petra LeBeau, Katy Jaffee, Cynthia M. Visness, William W. Busse, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2018)
Multiomic molecular comparison of primary versus metastatic pancreatic tumors.
Authors: Gagandeep Brar, Edik Blais, R Joseph Bender, Jonathan Brody, Davendra Sohal, Subha Madhavan, Vincent J. Picozzi, Andrew Eugene Hendifar, Vincent M. Chung, David Halverson, Sameh Mikhail, Lynn McCormick Matrisian, Lola Rahib, Emanuel Petricoin, Michael J. Pishvaian
Journal: Journal of Clinical Oncology (2018)

213 Background: Pancreatic cancer metastasizes very early, as evidenced by the fact that &gt; 70% of patients with operable disease ultimately develop metastases. Thus, it is likely that the molecular characteristics of primary pancreatic tumors are similar to metastatic lesions. We compared the frequency of genetic alterations and protein expression from primary vs. metastatic pancreatic tumors, and from metastases from different sites. By focusing on actionable genetic and proteomic information, we sought to explore whether targeted therapies could be tailored to patients at metastatic progression based on primary surgical material. Methods: Next generation DNA sequencing (NGS) data of 208 genes and a limited set of protein markers were analyzed from pancreatic tumors of 431 patients enrolled in the Know Your Tumor initiative. Of the 208 genes tested, mutations in 70 were considered potentially actionable based on preclinical and clinical evidence. We compared 146 primary pancreatic tumors against 285 metastatic lesions, and examined subgroups for liver vs. lung vs. other metastatic lesions. Molecular alterations were compared between independent groups for each gene/protein using Fisher’s exact test. Significance was assessed using a false discovery rate adjusted q-value threshold of 0.05. Results: No differences in the specific mutation or expression pattern were observed between primary vs. metastatic lesions, nor across the site of metastasis after correcting for multiple hypotheses. Even the proportion of actionable alterations (including mutations in the homologous recombination DNA repair pathway) was similar across subgroups. Conclusions: Comparison of the muli-omic profile of primary vs. metastatic pancreatic adenocarcinoma reveals that the molecular architecture is very similar, and that actionable alterations are identified at the same frequency. This is unlike the data observed from other solid tumors, (e.g. colon and breast cancer), in which substantial molecular discordance and heterogeneity exists between primary tumors and metastatic sites, but is consistent with the belief that primary pancreatic cancers metastasize early and thus are molecularly indistinguishable from metastatic lesions.
INDEPENDENT PREDICTORS OF LIPID-LOWERING THERAPY INTENSIFICATION AMONG PATIENTS HOSPITALIZED FOR AN ACUTE CORONARY SYNDROME: INSIGHTS FROM THE AMI-OPTIMA STUDY
Authors: Thao Huynh, Martine Montigny, Michel Nguyen, Mark Eisenberg, Claude Lauzon, Samer Mansour, Stéphane Rinfret, Marc Afilalo, Simon Kouz, Jean-Pierre Dery, Philippe L’Allier, Erick Schampaert, Jean Claude Tardif
Journal: Journal of the American College of Cardiology (2018)
Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species
Authors: Robert Lowe, Carl Barton, Christopher A. Jenkins, Christina Ernst, Oliver Forman, Denise S. Fernandez-Twinn, Christoph Bock, Stephen J. Rossiter, Chris G. Faulkes, Susan E. Ozanne, Lutz Walter, Duncan T. Odom, Cathryn Mellersh, Vardhman K. Rakyan
Journal: Genome biology (2018)

Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species. A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu. Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals.
A novel generation 1928zT2 CAR T cells induce remission in extramedullary relapse of acute lymphoblastic leukemia
Authors: Jianyu Weng, Peilong Lai, Le Qin, Yunxin Lai, Zhiwu Jiang, Chenwei Luo, Xin Huang, Suijing Wu, Dan Shao, Chengxin Deng, Lisi Huang, Zesheng Lu, Maohua Zhou, Lingji Zeng, Dongmei Chen, Yulian Wang, Xiaomei Chen, Suxia Geng, Weinkove Robert, Zhaoyang Tang, Chang He, Peng Li, Xin Du
Journal: Journal of Hematology & Oncology (2018)

Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its efficacy in B-ALL patients with extramedullary involvement is limited due to poor responses and neurotoxicity. Here, we utilized a third generation of CAR T cell vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with extramedullary involvement. 1928zT2 T cells were generated by 19-28z-TLR2 lentiviral vector transfection into primary human T lymphocytes. The anti-leukemia effect of 1928zT2 T cells were determined by killing assays and in xenografts. Three patients diagnosed as relapse or refractory ALL with extramedullary involvement were infused with 1928zT2 T cells, and the clinical responses were evaluated by BM smear, B-ultrasonography, PET/CT, histology, flow cytometry, qPCR, ELISA, and luminex assay. 1928zT2 T cells exhibited enhanced effector function against CD19+ leukemic cells in vitro and in a xenograft model of human extramedullary leukemia. Notably, the 1928zT2 T cells eradicated extramedullary leukemia and induced complete remission in the three relapse and refractory ALL patients without serious adverse effects. 1928zT2 T cells expanded robustly in the circulation of these three patients and were detected in the cerebrospinal fluid of patient 3. These three patients experienced cytokine release syndrome (CRS) with grade 2 or 3, which remitted spontaneously or after tocilizumab treatment. None of the three patients suffered neurotoxicity or needed further intensive care. Our results demonstrate that 1928zT2 T cells with TLR2 incorporation augment anti-leukemic effects, particularly for eradicating extramedullary leukemia cells, and suggest that the infusion of 1928zT2 T cells is an encouraging treatment for relapsed/refractory ALL patients with extramedullary involvement. ClinicalTrials.gov identifier NCT02822326. Date of registration: July 4, 2016.
Abstract P1-12-02: Clinical efficacy of a humanized monoclonal antibody against the Lewis-Y antigen (Ley): Results of a phase II clinical trial
Authors: L Testa, SV Serrano, RJ Arai, MC Zorzetto, R Freitas-Junior, O Maletz, MS Mano, PM Hoff
Journal: Cancer Research (2018)

Abstract Background. The Lewis-Y (Ley) antigen is a blood group-related antigen expressed in over 70% of epithelial cancers. It is expressed in 44% of breast cancers. Objectives. The primary endpoint was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in advanced hormone positive breast cancer after failure of at least one line of endocrine therapy. Methods. This multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). Results. Of 49 patients screened, 27 (55%) were Ley positive. Of these 27, only 20 were eligible for efficacy analysis. No complete or partial responses were observed. Five patients had stable disease for 24+ weeks (clinical benefit rate 25%). One patient remains on study drug maintaining stable disease for over 2 years. This patient had high expression of Ley. The most common treatment-related adverse events were headache (50%), cough (45,5%) and nausea/vomiting (31,8%). Conclusions. Hu3S193 lacked sufficient activity in is trial and the investigators stopped accrual at the first interim analysis. High expression of Ley might play a role in selecting patients to this strategy. Citation Format: Testa L, Serrano SV, Arai RJ, Zorzetto MC, Freitas-Junior R, Maletz O, Mano MS, Hoff PM. Clinical efficacy of a humanized monoclonal antibody against the Lewis-Y antigen (Ley): Results of a phase II clinical trial [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 P1-12-02.
I am a 40 year old registered osteopath who qualified in the United Kingdom in 1986. I am interested in pursuing a career in medicine. What courses would I be eligible to apply for, given my age?
Authors: Kuntal Patel
Journal: BMJ (2005)

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>
Medical ophthalmology training places should be increased, says Centre for Workforce Intelligence
Authors: Abi Rimmer
Journal: BMJ (2014)

The Centre for Workforce Intelligence has recommended an increase in medical ophthalmology third year specialty training (ST3) places in England.

In a report published last month the centre recommended that in 2014 ST3 posts in medical ophthalmology should be increased to five and maintained at that level until 2018.1

Medical ophthalmologists are trained to specialist level in general medicine and ophthalmology. They diagnose and manage …
Concurrent Alterations in EGFR-Mutant Lung Cancers Associated with Resistance to EGFR Kinase Inhibitors and Characterization of MTOR as a Mediator of Resistance
Authors: Helena A. Yu, Ken Suzawa, Emmet Jordan, Ahmet Zehir, Ai Ni, Ryan Kim, Mark G. Kris, Matthew D. Hellmann, Bob T. Li, Romel Somwar, David B. Solit, Michael F. Berger, Maria Arcila, Gregory J. Riely, Marc Ladanyi
Journal: Clinical Cancer Research (2018)

To identify molecular factors that determine duration of response to EGFR tyrosine kinase inhibitors and to identify novel mechanisms of drug resistance, we molecularly profiled
The <scp>PARACELSUS</scp> score: a novel diagnostic tool for pyoderma gangrenosum
Authors: F. Jockenhöfer, U. Wollina, K.A. Salva, S. Benson, J. Dissemond
Journal: British Journal of Dermatology (2018)

The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder. To develop and assess a comprehensive, yet clinically practicable, sensitive diagnostic scoring system for PG. Clinical history and images of a total of 60 participants with previously confirmed PG located on the lower extremity and a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of 10 criteria. The three major diagnostic criteria are rapidly progressing disease, assessment of relevant differential diagnoses and a reddish‐violaceous wound border (prevalent in 98% of patients with PG). Minor criteria (evident in 61–95% of patients with PG) include amelioration by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain > 4/10 on a visual analogue scale and localization of lesion at the site of the trauma. Three additional criteria (observed in up to 60% of patients with PG) encompass suppurative inflammation in histopathology, undermined wound borders and systemic disease associated. A total score value of 10 points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above‐listed criteria form the acronym PARACELSUS. The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.
Cancer diagnosis in patients with heart failure: epidemiology, clinical implications and gaps in knowledge
Authors: Pietro Ameri, Marco Canepa, Markus S. Anker, Yury Belenkov, Jutta Bergler‐Klein, Alain Cohen‐Solal, Dimitrios Farmakis, Teresa López‐Fernández, Mitja Lainscak, Radek Pudil, Frank Ruschitska, Petar Seferovic, Gerasimos Filippatos, Andrew Coats, Thomas Suter, Stephan Von Haehling, Fortunato Ciardiello, Rudolf A. de Boer, Alexander R. Lyon, Carlo G. Tocchetti
Journal: European Journal of Heart Failure (2018)
London Live Endoscopy course
Authors: Aruchuna Mohanaruban
Journal: BMJ (2013)

London Live Endosocopy is an interactive two day course which covers all aspects of interventional oesophagogastric and pancreaticobiliary medicine. The course is targeted mainly at consultants and senior specialist registrars practising advanced endoscopy.

The course is held annually at University College Hospital London and is endorsed by the British Society of Gastroenterologists and the European Society of Gastrointestinal Endoscopy. It is run by a faculty of gastroenterologists with a wealth of knowledge and skills in interventional endoscopy.

The course centred on live endoscopy cases, with two endoscopy rooms running in …
Surgical approaches—upper and lower limb course for surgical trainees
Authors: Ashish Soni, Muhammad Ul Haq
Journal: BMJ (2009)

The surgical approaches—upper and lower limb course for surgical trainees is run at the Royal College of Surgeons of England. It is based on the procedures laid out in the orthopaedic competency assessment project curriculum for skills at specialty training (ST) year 3-6 level. Developing an overall understanding of the basic principles behind different surgical approaches to upper and lower limbs is one of the main focuses of the course.

The course is designed primarily for ST3 and ST4 surgical trainees who wish to gain a thorough understanding of the three dimensional anatomy underlying common surgical approaches to the upper and lower limb. There was a mix of trainees attending the course from ST1 to ST6 level, including overseas trainees.

I did the course to prepare myself for my ST3 job. At this level one is expected to know the various common approaches to upper and lower limb surgery. With decreasing training hours in surgery, there …