tbuckley/cabot-search huggingface dataset:
BMA Scotland highlights poor GP premises
Authors: Helen Jaques
Journal: BMJ (2012)

The lack of a coherent premises strategy for general practice in Scotland is limiting the ability of GPs to develop local services, BMA Scotland’s General Practitioners Committee has said.

GPs are concerned that the Scottish government’s approach to primary care premises doesn’t devote sufficient attention to developing premises in areas where they are needed, the BMA says in its review of general practice in Scotland . 

“As Scotland’s population continues to …
Mirror Movements in a Patient With Brain Tumor
Authors: Leon D. Kaulen, Joachim M. Baehring
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Under what circumstances could I prescribe a drug on an FP10 script for my personal use?
Authors: Brian Keighley
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
Case 6-2018: A 35-Year-Old Woman with Headache, Subjective Fever, and Anemia
Authors: Steven J. Knuesel, J. Sawalla Guseh, Rebecca Karp Leaf, Andrea L. Ciaranello, George M. Eng
Journal: New England Journal of Medicine (2018)

A 35-year-old woman presented with headache, subjective fever, and anemia. She had a hematocrit of 18.1% and a reticulocyte count of less than 0.5%. Ten days before admission, her 3-year-old son had had a febrile illness. Diagnostic tests were performed.
An observational study profiling biospecimens from 10,000 metastatic prostate cancer (mPCa) patients to screen for molecular alterations.
Authors: Won Kim, Kat Kwiatkowski, Justin Brown, Dan R Rhodes, Scott A Tomlins, Felix Y Feng, Eric Jay Small
Journal: Journal of Clinical Oncology (2018)

TPS402 Background: Despite recent success in development and use of targeted agents in patients with solid tumors, there is a paucity of such therapies approved for use in prostate cancer. This observational study provides next-generation sequencing (NGS) to men with mPCa to evaluate the proportion of patients available for targeted therapy clinical trials in mPCa and to assess the feasibility of using a large-scale NGS screening program to match patients for eligibility criteria in clinical trials. Methods: Using a virtual clinical trial model to maximize patient access and enrollment, this study is providing next-generation sequencing (NGS) to 10,000 men with mPCa. Patients with histologically-documented mPCa and surplus formalin-fixed paraffin-embedded tumor tissue are eligible for enrollment. Leftover archival tissue is submitted for NGS to Strata Oncology, a clinical laboratory improvement amendments (CLIA)-certified lab. The StrataNGS assay sequences DNA and RNA, and simultaneously detects a range of actionable genomic alterations including gene mutations, small insertions and deletions, copy number changes, and gene fusions in 87 cancer-related genes. Microsatellite instability status is determined via the number of length variant alleles observed in NGS sequencing data at several microsatellite loci. Test reports presented to the clinician include all positive and negative variants detected, and information about potential matching therapeutic protocols. Clinical trial information: NCT03061305.
Prehospital anaesthetic course
Authors: Rachel Hawes
Journal: BMJ (2010)

With the expected introduction of prehospital emergency medicine as a specialty in its own right and a curriculum under development, this two day course aims to cover the knowledge, skills, and human factors required for prehospital care practitioners to perform emergency anaesthesia safely in the prehospital environment.

Any doctor, paramedic, or nurse who currently performs or assists with prehospital rapid sequence induction (RSI) or wishes to train in this area. The current national guidelines1 suggest that a minimum level of experience for doctors wishing to train in prehospital anaesthesia is equivalent …
Effect of chimeric antigen receptor-modified T (CAR-T) cells on responses in children with non-CNS extramedullary relapse of CD19+ acute lymphoblastic leukemia (ALL).
Authors: Mala Kiran Talekar, Shannon L. Maude, George E Hucks, Laura S Motley, Colleen Callahan, Claire M White, Diane Baniewicz, David Maxwell Barrett, Susan R. Rheingold, Simon F. Lacey, Bruce L Levine, Jan J. Melenhorst, David T. Teachey, Carl H. June, Stephan A. Grupp
Journal: Journal of Clinical Oncology (2017)

10507 Background: Anti-CD19 CAR-T cell therapies have shown high efficacy in inducing durable marrow responses in patients with relapsed/refractory CD19+ ALL. We now report on outcome of 10 patients with extramedullary (EM) involvement of ALL treated with CAR-T, including 5 patients who had EM disease at time of infusion. Methods: We identified patients treated on pediatric phase 1/2a trials of murine (CTL019) or humanized (CTL119) anti-CD19 CAR-T cells for isolated EM or BM/EM relapse of ALL. EM relapse was defined as involvement of non-CNS site by imaging +/- pathology within 12 months (mos) of infusion. Post infusion, patients had diagnostic imaging done at 1, 3, 6, 9, and 12 mos. Results: Among 97 patients receiving CAR-T, ten (CTL019, n=6; CTL119, n=4) were identified who had EM involvement on average 2.3 mos (range 0-9 mos) prior to infusion; including 5/10 at time of infusion. Sites of EM relapses included testes, sinus, parotid, bone, uterus, kidney and skin, and 5 patients had multiple sites of EM involvement. Patients ranged from 2-4 relapses of their ALL pre-CAR-T. Two had isolated EM relapse (sites were parotid and multifocal bony lesions in one; testis and sinus in second). All 10 patients had undergone hematopoietic stem cell transplantation prior to EM relapse, 2 had received radiation directed to the EM site prior to CAR-T. Five patients evaluated by serial imaging had objective responses: 2 had resolution of EM disease by day 28; 2 had resolution by 3 mos; 1 had continued decrease in size of uterine mass at 3 and 6 mos and underwent hysterectomy at 8 mos with no evidence of disease on pathology. In the 4 patients with prior history of skin or testicular involvement, there was no evidence by exam at day 28. One patient had progressive EM disease within 2 weeks of CAR-T cell infusion and died at 6 weeks. Three relapsed with CD19+ disease [1 skin/medullary- died at 38 mos post CAR-T; 2 medullary (1 died at 17 mos, 1 alive at 28 mos)]. The remaining 6 are alive and well at median follow-up of 10 mos (range 3-16 mos) without recurrence of disease. Conclusions: Single agent CAR-T immunotherapy can induce potent and durable responses in patients with EM relapse of their ALL. Clinical trial information: NCT01626495, NCT02374333.
Abstract P2-10-06: Identifying patients sensitive to anthracycline-containing therapy with quantitative proteomic and genomic profiling
Authors: S Schwartz, F Cecchi, Y Tian, C Yau, C Szeto, M Rübner, R Erber, MW Beckmann, A Hartmann, S Benz, T Hembrough, P Fasching
Journal: Cancer Research (2018)

Abstract Background: Selecting chemotherapy based on tumor biology can improve response rates and avert toxicity. Studies of the relationship between tumor expression of TOP2A protein and response to anthracycline-based chemotherapy have yielded contradictory results. Here we used mass spectrometry (MS) to evaluate associations between tumor molecular profiles and pathological complete response (pCR) in breast cancer patients treated with neoadjuvant anthracycline-containing therapy. Methods: Patients were selected from the ERNEST-B (Erlangen Neoadjuvant Study Breast), which is a retrospective cohort study. Archived tumor samples from anthracycline-treated breast cancer patients (n=133) were microdissected and solubilized. In each tumor sample, TOP2A and other target proteins were quantitated with a mass spectrometry assay. Molecular profiling also included RNA sequencing of the tumor and whole genome sequencing of both tumor and matched normal tissue sections. The cohort was dichotomized into high and low expressors of TOP2A using a protein level cutoff of 515 amol/ug of tumor protein. The difference in pCR (ypT0ypN0) rates between high and low expressors of TOP2A was assessed using a z-test for differences in proportion. Results: TOP2A protein was detected in 84 of 133 (63%) tumor samples from anthracycline-treated patients (range: 178 to 3044 amol/ug). Patients whose tumor expressed TOP2A protein above the cutoff of 515 amol/ug had higher pCR rates than patients with lower TOP2A expression (35.5% vs. 12.1%; odds ratio (OR): 4.48 [95% CI: 1.53-13.28], Fisher' exact test p = 0.004). The difference retained statistical significance in a logistic regression model adjusting for HR and HER2 status (OR: 2.23 [95% CI: 1.15-4.30], p=0.017). In a separate cohort of 19 breast cancer patients who did not receive anthracycline, there was no association between TOP2A protein expression level and pCR rate. Results from a validation cohort as well as the genomic analysis will be presented at the meeting. Conclusions: In a retrospective analysis of anthracycline-treated breast tumors, TOP2A expression was associated with a higher rate of pCR. Targeted proteomics may predict the response of breast cancer patients to anthracycline-based therapy. Citation Format: Schwartz S, Cecchi F, Tian Y, Yau C, Szeto C, Rübner M, Erber R, Beckmann MW, Hartmann A, Benz S, Hembrough T, Fasching P. Identifying patients sensitive to anthracycline-containing therapy with quantitative proteomic and genomic profiling [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 P2-10-06.
Evolution of Unilateral Basal Ganglia Lesion Over 16 Months
Authors: Xin Lou, Chenglin Tian, Lin Ma
Journal: JAMA Neurology (2018)

An adolescent boy presented with cognitive and behavioral changes, headaches, and progressively worsening weakness of the left arm and leg. On magnetic resonance imaging, a lesion in the right basal ganglia discovered 16 months previously appeared larger. What is your diagnosis?
FRACTIONAL FLOW RESERVE AND INSTANTANEOUS WAVE-FREE RATIO TO GUIDE CORONARY ARTERY BYPASS GRAFTING
Authors: John Moscona, Jason Stencel, Gregory Milligan, Christopher Salmon, Rohit Maini, Paul Katigbak, Ryan Nelson, Sudesh Srivastav, Owen Mogabgab, Rohan Samson, Thierry Le Jemtel
Journal: Journal of the American College of Cardiology (2018)
BIOIMPEDANCE PHASE ANGLE AS A BIOMARKER FOR FRAILTY AND PREDICTOR OF MORTALITY IN CARDIAC SURGERY
Authors: Louis Antoine Mullie, Alexandrine O’Brand, Melissa Bendayan, Emmanuel Moss, Jean-François Morin, Yves Langlois, Felix Ma, Kevin Lachapelle, Renzo Cecere, Benoit de Varennes, Christo Tchervenkov, Lawrence Rudski, Amanda Trnkus, Jonathan Afilalo
Journal: Journal of the American College of Cardiology (2018)
Phase II trial of palbociclib in patients with advanced esophageal or gastric cancer.
Authors: Thomas Benjamin Karasic, Mark H. O'Hara, Ursina R. Teitelbaum, Nevena Damjanov, Bruce J. Giantonio, Tracy S. d'Entremont, Maryann Gallagher, Paul J. Zhang, Peter J. O'Dwyer
Journal: Journal of Clinical Oncology (2018)

68 Background: Dysregulation of the cell cycle is a hallmark of cancer. Progression through the G1/S transition requires phosphorylation of retinoblastoma (RB) by cyclin-dependent kinases 4 and 6 (CDK4/6), which are regulated by cyclins D and E. A positive feedback loop between apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase pathway, and cyclin D1 has been shown to drive cell proliferation in gastric cancer. In addition, amplification of cyclin D loci and/or activating mutations in CDKs are frequent molecular aberrations in gastroesophageal malignancies. We hypothesized that palbociclib, a potent inhibitor of CDK4/6 would disrupt proliferative signaling, and arrest the growth of gastric cancer. We conducted a phase II trial of palbociclib in gastric and esophageal cancers as an initial test of efficacy. Methods: We screened 38 subjects with gastric, GE junction, or esophageal cancer for RB nuclear expression by immunohistochemistry, and 38/38 (100%) were positive. We enrolled 21 subjects, of whom 5 had gastric adenocarcinoma, 3 had GE junction adenocarcinoma, 8 had esophageal adenocarcinoma, and 5 had esophageal squamous cell carcinoma. Four of 19 subjects tested positive for CCND1 overexpression by FISH. Patients received 125mg daily of palbociclib for days 1-21 of 28-day cycles. Results: Subjects remained on treatment for a median of 1.7 months. By the initial 2-month assessment, 5 of 21 subjects had stable disease, and 16 subjects had progressive disease by imaging and/or clinical progression. No objective responses were seen. The maximum duration of therapy was 5.5 months in two subjects. One of these subjects had progressing HER2-amplified gastric adenocarcinoma, and continued concurrent trastuzumab with palbociclib, while the other had squamous cell carcinoma of the esophagus. Grade 3 or 4 cytopenias occurred in 9 of 21 subjects (43%), with neutropenia in 8 (38%), anemia in 4 (19%), and thrombocytopenia in 1 (5%). One subject discontinued therapy due to grade 4 thrombocytopenia with GI bleed. All other subjects discontinued therapy due to disease progression. Conclusions: Palbociclib has modest single-agent activity in gastroesophageal tumors despite universal RB expression. Clinical trial information: NCT01037790.
DNA Methylation Signatures Predicting Bevacizumab Efficacy in Metastatic Breast Cancer
Authors: Simon Peter Gampenrieder, Gabriel Rinnerthaler, Hubert Hackl, Walter Pulverer, Andreas Weinhaeusel, Suzana Ilic, Clemens Hufnagl, Cornelia Hauser-Kronberger, Alexander Egle, Angela Risch, Richard Greil
Journal: Theranostics (2018)

Background: Biomarkers predicting response to bevacizumab in breast cancer are still missing.Since epigenetic modifications can contribute to an aberrant regulation of angiogenesis and treatment resistance, we investigated the influence of DNA methylation patterns on bevacizumab efficacy.Methods: Genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in archival FFPE specimens of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy (learning set).Based on objective response and progression-free survival (PFS) and considering ER expression, patients were divided in responders (R) and non-responders (NR).Significantly differentially methylated gene loci (CpGs) with a strong change in methylation levels (Δβ>0.15 or Δβ<-0.15) between R and NR were identified and further investigated in 80 bevacizumab-treated breast cancer patients (optimization set) and in 15 patients treated with chemotherapy alone (control set) using targeted deep amplicon bisulfite sequencing.Methylated gene loci were considered predictive if there was a significant association with outcome (PFS) in the optimization set but not in the control set using Spearman rank correlation, Cox regression, and logrank test.Results: Differentially methylated loci in 48 genes were identified, allowing a good separation between R and NR (odds ratio (OR) 101, p<0.0001).Methylation of at least one cytosine in 26 gene-regions was significantly associated with progression-free survival (PFS) in the optimization set, but not in the control set.Using information from the optimization set, the panel was reduced to a 9-gene signature, which could divide patients from the learning set into 2 clusters, thereby predicting response with an OR of 40 (p<0.001) and an AUC of 0.91 (LOOCV).A further restricted 3-gene methylation model showed a significant association of predicted responders with longer PFS in the learning and optimization set even in multivariate analysis with an excellent and good separation of R and NR with AUC=0.94 and AUC=0.86,respectively.Conclusion: Both a 9-gene and 3-gene methylation signature can discriminate between R and NR to a bevacizumab-based therapy in MBC and could help identify patients deriving greater benefit from bevacizumab.
Emergency skills in oral and maxillofacial surgery
Authors: Niroshan Sivathasan
Journal: BMJ (2012)

Emergencies in maxillofacial surgery can be daunting experiences for doctors, because many can rapidly progress into life threatening situations. They particularly revolve around airway compromise and haemorrhage, which together contribute to the key three letter moniker known to all doctors—ABC—airway and C-spine stabilisation, breathing, and circulation.

This course aims to make junior doctors who manage patients in the ward and in the operating theatre familiar with emergency situations handled by oral and maxillofacial surgeons.

This two day course is targeted at doctors at the levels of senior house officer (core trainee years 1 and 2) and junior registrar (specialty trainee years 3 and 4). It would probably be of limited value to doctors below the level of senior house officer (that is, foundation years 1 and 2), unless they have previous experience in maxillofacial surgery (such as dentists who have subsequently read medicine). Equally, those above specialty trainee year 4 are unlikely to gain considerable benefit from this course.

Completion of the advanced …
Hierarchical Design of Tissue Regenerative Constructs
Authors: Jonas C. Rose, Laura De Laporte
Journal: Advanced Healthcare Materials (2018)

Abstract The worldwide shortage of organs fosters significant advancements in regenerative therapies. Tissue engineering and regeneration aim to supply or repair organs or tissues by combining material scaffolds, biochemical signals, and cells. The greatest challenge entails the creation of a suitable implantable or injectable 3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell‐induced tissue formation. This review gives an overview of the essential components of tissue regenerating scaffolds, ranging from the molecular to the macroscopic scale in a hierarchical manner. Further, this review elaborates about recent pivotal technologies, such as photopatterning, electrospinning, 3D bioprinting, or the assembly of micrometer‐scale building blocks, which enable the incorporation of local heterogeneities, similar to most native extracellular matrices. These methods are applied to mimic a vast number of different tissues, including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the tremendous progress that has been made in the last decade, it remains a hurdle to build biomaterial constructs in vitro or in vivo with a native‐like structure and architecture, including spatiotemporal control of biofunctional domains and mechanical properties. New chemistries and assembly methods in water will be crucial to develop therapies that are clinically translatable and can evolve into organized and functional tissues.
I am a doctor in India with PLAB part 1 and an MD in clinical biochemistry. How should I go about applying for a training post in clinical biochemistry (chemical pathology) in the United Kingdom?
Authors: Adrian Park
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 (www.bmjcareers.com/advicezone) 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.
I am a British-qualified doctor, who completed MRCP and then left to work in intensive care in Hong Kong for ten years. I have now returned to Berkshire and wish to change specialty, preferably moving into general practice. Which deanery gives the best information and where else can I find advice?
Authors: Rodger Charlton
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth
Authors: Mami Morita, Taku Sato, Miyuki Nomura, Yoshimi Sakamoto, Yui Inoue, Ryota Tanaka, Shigemi Ito, Koreyuki Kurosawa, Kazunori Yamaguchi, Yuki Sugiura, Hiroshi Takizaki, Yoji Yamashita, Ryuichi Katakura, Ikuro Sato, Masaaki Kawai, Yoshinori Okada, Hitomi Watanabe, Gen Kondoh, Shoko Matsumoto, Ayako Kishimoto, Miki Obata, Masaki Matsumoto, Tatsuro Fukuhara, Hozumi Motohashi, Makoto Suematsu, Masaaki Komatsu, Keiichi I. Nakayama, Toshio Watanabe, Tomoyoshi Soga, Hiroshi Shima, Makoto Maemondo, Nobuhiro Tanuma
Journal: Cancer Cell (2018)
RACIAL DIFFERENCES IN OUTCOMES BETWEEN AFRICAN AMERICANS AND NON-AFRICAN AMERICANS ADMITTED FOR CONGESTIVE HEART FAILURE: A NATIONWIDE ANALYSIS
Authors: Xin Wei, Yibin Guo, Kevin Gu, Bing Yue, Ahmadreza Moradi, Chayakrit Krittanawong, Basera Sabharwal, Mariam Khandaker, Karan Sud, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
EARLY DETECTION OF RIGHT VENTRICULAR DYSFUNCTION ASSESSED BY TWO-DIMENSIONAL SPECKLE-TRACKING ECHOCARDIOGRAPHY IN ADULT LYMPHOMA PATIENTS RECEIVING ANTHRACYCLINE-BASED CHEMOTHERAPY
Authors: Ahmad S. Manshad, Fatima A. Ballout, Tochukwu M. Okwuosa
Journal: Journal of the American College of Cardiology (2018)
Publisher Correction: Whole genome sequencing in psychiatric disorders: the WGSPD consortium
Authors: Stephan J. Sanders, Benjamin M. Neale, Hailiang Huang, Donna M. Werling, Joon-Yong An, Shan Dong, Goncalo Abecasis, P. Alexander Arguello, John Blangero, Michael Boehnke, Mark J. Daly, Kevin Eggan, Daniel H. Geschwind, David C. Glahn, David B. Goldstein, Raquel E. Gur, Robert E. Handsaker, Steven A. McCarroll, Roel A. Ophoff, Aarno Palotie, Carlos N. Pato, Chiara Sabatti, Matthew W. State, A. Jeremy Willsey, Steven E. Hyman, Anjene M. Addington, Thomas Lehner, Nelson B. Freimer
Journal: Nature Neuroscience (2018)
Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction
Authors: Long V. Le, Priya Mohindra, Qizhi Fang, Richard E. Sievers, Michael A. Mkrtschjan, Christopher Solis, Conrad W. Safranek, Brenda Russell, Randall J. Lee, Tejal A. Desai
Journal: Biomaterials (2018)