tbuckley/cabot-search huggingface dataset:
What does it take to become a specialist registrar in clinical radiology? How long will it take to become a specialist registrar after working in the senior house officer grade?
Authors: John Frank
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>
NHS needs local pay schemes to stay financially afloat, Foundation Trust Network says
Authors: Helen Jaques
Journal: BMJ (2013)

NHS staff and managers “urgently” need to debate regional pay variation to keep the NHS afloat financially and improve the quality of care, the head of the Foundation Trust Network has said. 

Chris Hopson, the network’s chief executive, said that hospital trusts were facing new financial challenges as they tried to cope with rising demand and costs in the face of flat funding. Trusts were also grappling with the drive to make £11m of efficiency savings a year and with the …
Molecular Genetic Analysis Subdivided by Adversity Exposure Suggests Etiologic Heterogeneity in Major Depression
Authors: Roseann E. Peterson, Na Cai, Andy W. Dahl, Tim B. Bigdeli, Alexis C. Edwards, Bradley T. Webb, Silviu-Alin Bacanu, Noah Zaitlen, Jonathan Flint, Kenneth S. Kendler
Journal: American Journal of Psychiatry (2018)

Objective: The extent to which major depression is the outcome of a single biological mechanism or represents a final common pathway of multiple disease processes remains uncertain. Genetic approaches can potentially identify etiologic heterogeneity in major depression by classifying patients on the basis of their experience of major adverse events. Method: Data are from the China, Oxford, and VCU Experimental Research on Genetic Epidemiology (CONVERGE) project, a study of Han Chinese women with recurrent major depression aimed at identifying genetic risk factors for major depression in a rigorously ascertained cohort carefully assessed for key environmental risk factors (N=9,599). To detect etiologic heterogeneity, genome-wide association studies, heritability analyses, and gene-by-environment interaction analyses were performed. Results: Genome-wide association studies stratified by exposure to adversity revealed three novel loci associated with major depression only in study participants with no history of adversity. Significant gene-by-environment interactions were seen between adversity and genotype at all three loci, and 13.2% of major depression liability can be attributed to genome-wide interaction with adversity exposure. The genetic risk in major depression for participants who reported major adverse life events (27%) was partially shared with that in participants who did not (73%; genetic correlation=+0.64). Together with results from simulation studies, these findings suggest etiologic heterogeneity within major depression as a function of environmental exposures. Conclusions: The genetic contributions to major depression may differ between women with and those without major adverse life events. These results have implications for the molecular dissection of major depression and other complex psychiatric and biomedical diseases.
Seizure-Induced Increased 18F-DOPA Uptake in a Child With Diffuse Astrocytoma and Transient Brain MRI Abnormalities Related to Status Epilepticus
Authors: Giovanni Morana, Gianluca Bottoni, Maria Margherita Mancardi, Antonio Verrico, Arnoldo Piccardo
Journal: Clinical Nuclear Medicine (2018)

Abstract We report the finding of increased 18 F-DOPA uptake in the brain parenchyma surrounding a temporoparietal low-grade diffuse astrocytoma and corresponding to transient seizure-induced MRI abnormalities. There was concomitant markedly increased tumoral uptake. This 18 F-DOPA PET phenomenon may represent increased amino acid transport induced by seizures. In the setting of brain tumor imaging, increased 18 F-DOPA uptake of low-grade epileptogenic tumors and adjacent brain parenchyma should be carefully interpreted in light of clinical and electroencephalographic findings related to seizure activity.
CLINICAL EFFECTS OF LOW SPEED ROTATIONAL ATHERECTOMY ON THE POST-INTERVENTIONAL MICROCIRCULATION
Authors: Takayuki Ishihara, Osamu Iida, Mitsutoshi Asai, Masaharu Masuda, Shin Okamoto, Kiyonori Nanto, Takashi Kanda, Takuya Tsujimura, Shota Okuno, Yasuhiro Matsuda, Takuya Ohashi, Hiroyuki Kawai, Aki Tsuji, Yosuke Hata, Yuki Sato, Hiroyuki Uematsu, Toshiaki Mano
Journal: Journal of the American College of Cardiology (2018)
Geranylgeranyl pyrophosphate synthase facilitates the organization of cardiomyocytes during mid-gestation through modulating protein geranylgeranylation in mouse heart
Authors: Zhong Chen, Na Xu, Danyang Chong, Shan Guan, Chen Jiang, Zhongzhou Yang, Chaojun Li
Journal: Cardiovascular Research (2018)

With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodelling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied.Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function. By using different Cre lines, we found that the cardiac inactivation of Ggpps by the Nkx2.5Cre/+ line disrupted protein geranylgeranylation as early as E9.5, which affected ventricular chamber maturation and resulted in mid-gestational embryonic lethality. In contrast, α-SMA-Cre line mediated the disruption of protein geranylgeranylation from E13.5 did not affect embryonic heart development. Further analysis of Nkx2.5Cre/+; Ggppsfl/fl mutants showed that the loss of Ggpps caused disorganized cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions. Ggpps inactivation decreased Rho GTPase geranylgeranylation and their activity, which might account for the disruption of cell-cell junctions. Moreover, elevating the protein geranylgeranylation by supplement of geranylgeranyl pyrophosphate (GGPP) could recover the Ggpps deficient induced defects of cytoarchitecture and cell-cell junctions in vitro and in vivo.Our present study demonstrates that GGPPS-mediated protein geranylgeranylation plays an indispensable role in the ventricular chamber maturation and acts as a stage-specific signal to regulate the establishment of cardiac cytoarchitecture during mid-gestation.
P058 S100 proteins effectively discriminate systemic lupus erythematosus patients from healthy controls, but are not associated with measures of disease activity
Authors: B Šumová, J Závada, LA Cerezo, M Uher, H Hulejová, M Grigorian, K Pavelka, J Vencovský, L Šenolt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The S100 proteins are important regulators of diverse calcium-dependent cellular processes including growth regulation, migration and apoptosis. Dysregulated expression of multiple members of S100 family is a common feature of cancer and several autoimmune diseases. <h3>Objectives</h3> The aim of this study was to examine whether circulating levels of S100A4, S100A8/9 and S100A12 proteins could be useful as diagnostic or activity specific markers in systemic lupus erythematosus (SLE). <h3>Methods</h3> S100 plasma levels were measured by ELISA in a cohort study of 44 patients with SLE, 8 patients with incomplete SLE (iSLE) and 43 healthy controls (HCs). Disease activity was assessed using SLEDAI-2 K. We examined cross sectional associations between concentrations of S100 proteins and SLE status, SLEDAI-2 K scores, and levels of conventional biomarkers. <h3>Results</h3> Plasma levels of all analysed S100 proteins (S100A4, S100A8/9 and S100A12) were significantly higher in SLE patients compared to HCs (p&lt;0.001, p&lt;0.01, p&lt;0.001, respectively). In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were significantly higher compared to HCs (p&lt;0.001, p&lt;0.05, p=ns, respectively). ROC curve analysis was performed to establish the optimal threshold to discriminate SLE patients from HCs based on S100 levels. At the optimal cutoff point of 238 ng/ml, the area under curve (AUC) for S100A4 was 0–990 (95% CI: 0.977 to 1.000, p&lt;0.001) with a sensitivity of 96% and specify of 93.0%. The remaining two proteins also showed significant, but not as strong discriminative value [S100A8/9: AUC 0.684 (95% CI: 0.572 to 0.795, p&lt;0.05); S100A12: AUC 0.809 (95% CI: 0.719 to 0.898, p&lt;0.001]. We found that only S100A12 levels were significantly associated with the SLEDAI-2K score (r=0.318, p=0.035). Both S100A8/9 and S100A12 levels were significantly higher in SLE patients with arthritis (p=0.043, p=0.015, respectively) and with haematological features (p=0.002 for both). There were no other significant associations between S100 levels and other conventional markers such as C3, C4 and the anti-dsDNA antibodies. <h3>Conclusions</h3> We demonstrate increased S100 proteins expression in SLE patients. Although they were not strongly associated with disease activity, S100 proteins and namely S100A4 could be proposed as a diagnostic biomarker for SLE. <h3>Acknowledgements</h3> MHCR for conceptual development of research organisation 00023728 and SVV 260 373. <h3>Disclosure of interest</h3> None declared
Royal college proposes “radical” shake up of obstetrics and gynaecology training and working patterns
Authors: Caroline White
Journal: BMJ (2012)

The training and work patterns of obstetricians and gynaecologists needs a radical rethink if high quality, affordable care for women throughout their lifespan is to be achieved, a report from the Royal College of Obstetricians and Gynaecologists has concluded.1

The present structure and system of healthcare delivery is unsustainable, inflexible, disjointed, and overly reliant on junior doctors and low grade service posts, argues the report.

It calls for more consultant led care round the clock to deal with complex cases and emergencies and for …
PREDICTORS OF DEATH WHILE ON VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION (VA-ECMO) SUPPORT
Authors: Anna Koulova, Venkata Buddharaju, Rudrick Ledesma, Savneek Chugh, Maureen Brogan, Julio Panza, Joshua Goldberg, Masashi Kai, Ramin Malekan, David Spielvogel, Wilbert Aronow, Chul Ahn, Alan Gass
Journal: Journal of the American College of Cardiology (2018)
Secret guidance for fitness to practise panels is withdrawn
Authors: Clare Dyer
Journal: BMJ (2014)

Secret guidance issued to interim fitness to practise panels has been withdrawn after permission was granted to challenge it in court.

A doctors’ defence organisation argued that adverse decisions may have been reached on the basis of erroneous instructions in the guidance. It added that doctors’ defence teams would not have been able to correct these instructions because the guidance was kept secret from them.

The Medical Practitioners Tribunal Service, which hears fitness to practise cases brought by the General Medical Council, withdrew the guidance after the Medical Protection Society won permission for an urgent High Court hearing to challenge it.

The guidance was included in a document distributed by the tribunal service titled “Circular 34/13.” The circular was issued on 17 December 2013, but doctors and their defence bodies became aware of it only when it was discovered …
RADIO FREQUENCY ABLATION IN CHILDREN IS SAFE AND EFFICIENT: DATA FROM THE SWEDISH NATIONAL CATHETER ABLATION REGISTRY
Authors: Fredrik Holmqvist, Per Insulander, Runa Sigurjonsdottir, Carina Blomström Lundqvist, Milos Kesek, Dritan Poci, Michael Ringborn, Romeo Samo-Ayou, Anders Englund, Csaba Herczku, Anders Jönsson
Journal: Journal of the American College of Cardiology (2018)
Abstract P2-10-01: Validation that a histone gene signature predicts anthracycline response in early breast cancer
Authors: M Spears, E Kornaga, N Lyttle, L Liao, J Bayani, M-A Quintayo, CQ Yao, A D'Costa, PC Boutros, CJ Twelves, KI Pritchard, MN Levine, TO Nielsen, L Shepherd, JMS Bartlett
Journal: Cancer Research (2018)

Abstract Background: The use of anthracycline-based chemotherapies has improved overall and disease free survival in breast cancer. However, anthracyclines can have significant toxicities including cardiotoxicity and leukemia. It is, therefore, imperative to identify those patients who will benefit from adjuvant anthracycline treatment and patients who could be spared unnecessary toxicities and be considered for alternative adjuvant therapy. Previous work performed by our laboratory identified a histone gene expression signature as a predictive marker of anthracycline benefit in the BR9601 clinical trial. In this study we validate the 18 histone gene signature in the MA.5 clinical trial and examine the role of the signature in individual intrinsic subtypes of breast cancer. Methods We analysed the CCTG MA.5 clinical trial in a prospectively planned retrospective biomarker approach to validate this signature and tested the role of intrinsic subtyping as predictive markers of anthracycline benefit. RNA was extracted from patients in the MA.5 adjuvant trial evaluating the addition of epirubicin (E) to CMF and analysed using NanoString technology. Log-rank analyses validated the predictive values of the signature on distant relapse-free survival (DRFS). Cox-regression models tested independent predictive value on DRFS in the presence of treatment, age, tumour size, nodal status, HER2, ER status and grade, and treatment by marker interactions. Results Analysis of the MA.5 clinical cohort revealed that patients whose tumour had low histone gene signature expression experienced increased DRFS (HR: 0.54, 95% CI 0.38-0.76, p=0.001) when treated with CEF compared with patients treated with CMF alone. Conversely, there was no apparent benefit of CEF vs CMF in patients with high histone gene expression signature (HR: 1.01, 95%CI 0.66-1.55, p=0.963). After multivariate analysis and adjustment for HER2, nodal status, age, grade and ER, the treatment by marker interaction for the gene signature was 0.54 (95%CI 0.31-0.94, p=0.030) for DRFS. The predictive impact of the histone signature was independent of intrinsic subtype. Conclusion The histone gene expression signature is an independent predictor of anthracycline benefit and could be a potential candidate diagnostic assay for patients with early breast cancer. Citation Format: Spears M, Kornaga E, Lyttle N, Liao L, Bayani J, Quintayo M-A, Yao CQ, D'Costa A, Boutros PC, Twelves CJ, Pritchard KI, Levine MN, Nielsen TO, Shepherd L, Bartlett JMS. Validation that a histone gene signature predicts anthracycline response in early 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 P2-10-01.
Radiofrequency ablation vs. surgery for perivascular hepatocellular carcinoma: Propensity score analyses of long-term outcomes
Authors: Sunyoung Lee, Tae Wook Kang, Dong Ik Cha, Kyoung Doo Song, Min Woo Lee, Hyunchul Rhim, Hyo Keun Lim, Dong Hyun Sinn, Jong Man Kim, Kyunga Kim
Journal: Journal of Hepatology (2018)
BMA to launch patient campaign to highlight “adverse effects” of government changes
Authors: Helen Jaques
Journal: BMJ (2013)

The BMA is launching a campaign to help GPs explain to patients how their care is being affected by changes imposed by the government, in particular NHS reorganisation and the new general medical services (GMS) contract.

The BMA’s General Practitioners Committee said that the goal of the campaign was to reassure patients that their GP would always provide the best possible care but that some recent changes to the health service in England imposed by the government might make that more difficult. 

Richard Vautrey, the committee’s deputy chairman, said that the …
THE UTILIZATION OF NON-INVASIVE ECHOCARDIOGRAPHIC INDICES IN ESTIMATING PULMONARY CAPILLARY WEDGE PRESSURE IN HEART TRANSPLANT PATIENTS
Authors: Mohammed A.R. Chamsi-Pasha, Brock Cookman, Shikhar Saxena, Samer Sayyed, Eugenia Raichlin
Journal: Journal of the American College of Cardiology (2014)
Red tape cut for consultants doing short term work at other organisations
Authors: Helen Jaques
Journal: BMJ (2013)

A new scheme will simplify and accelerate the approval process for consultants wishing to do short term, ad hoc, or urgent work at NHS organisations or universities other than their main employer.

The Certificate of Fitness for Honorary Practice avoids the need for an honorary contract of employment. It shows that a consultant has passed all the employment checks for short term work in other NHS trusts and hospitals. 

The current system for short term visits by practising consultants involves obtaining a full honorary contract and verifying the necessary employment checks, which …
On Don Quixote and pink puffers: multi-organ loss of tissue COPD
Authors: Joan B. Soriano, Pierre-Régis Burgel
Journal: European Respiratory Journal (2018)

" Del poco dormir y del mucho leer, se le secó el cerebro, de manera que vino a perder el juicio " [1]; that is, "From little sleep and much reading, his brain dried up, so he came to lose his mind". It is unknown whether Don Miguel de Cervantes, or his most famous character, Don Quixote, ever tried tobacco, at that time newly traded from the New World. However, we invite you to revisit Frank Netter's wonderful "pink puffer" and "blue bloater" illustrations [2], iconic images of the classical chronic obstructive pulmonary disease (COPD) phenotypes of emphysema and chronic bronchitis. Do they have any resemblance to Alonso Quijano (Don Quixote) and his best friend Mr Sancho Panza, respectively (figure 1) [3]? More research to explore the newly proposed MOLT phenotype in COPD is welcome <http://ow.ly/zkYR30hH4UP>
ANGIOGRAPHIC PREDICTORS OF LIPID RICH PLAQUE DETECTED BY NEAR-INFRARED SPECTROSCOPY: THE COLOR REGISTRY
Authors: Mitsuaki Matsumura, Giora Weisz, Myong-Hwa Yamamoto, Jordan Andrews, Annapoorna Subhash Kini, Emmanouil Brilakis, David Gerard Rizik, Simon Dixon, Nabil Dib, Priti Shah, Aaron Crowley, Stephen Nicholls, Gregg Stone, Gary Mintz, James Muller, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
Editor’s Choice: Questioning the status quo
Authors: Abi Rimmer
Journal: BMJ (2015)

Finding a solution to a problem is something doctors do every day. But when the problem is a longstanding practice or belief things can get difficult. This week BMJ Careers features doctors who have challenged the status quo. 

Amir Sam, Saira Hameed, and Karim Meeran (http://careers.bmj.com/careers/advice/Medical\_students\_are\_the\_physician%E2%80%99s_apprentices) find that the common practice of medical students “sitting in” in clinics actually provides them …
PHYLOSCANNER: Inferring Transmission from Within- and Between-Host Pathogen Genetic Diversity
Authors: Chris Wymant, Matthew Hall, Oliver Ratmann, David Bonsall, Tanya Golubchik, Mariateresa de Cesare, Astrid Gall, Marion Cornelissen, Christophe Fraser
Journal: Molecular Biology and Evolution (2017)

A central feature of pathogen genomics is that different infectious particles (virions and bacterial cells) within an infected individual may be genetically distinct, with patterns of relatedness among infectious particles being the result of both within-host evolution and transmission from one host to the next. Here, we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbor subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner.
More female than male doctors have had their revalidation deferred, GMC figures show
Authors: Abi Rimmer
Journal: BMJ (2014)

More female doctors have deferred their revalidation date than their male counterparts, data from the General Medical Council have shown. 

A progress report from the GMC’s revalidation implementation advisory board showed that the regulator had received 36 670 recommendations from responsible officers from 3 December 2012 to 31 January 2014.1 This equated to 16.1% of the 227 352 doctors who were currently subject to revalidation, the report said. 

Of the 36 670 recommendations received 30 565 (83.35%) were positive recommendations for a doctor to …
High dose interleukin-2 and response in 944 patients with metastatic renal cell cancer (RCC): Data from the PROCLAIM registry.
Authors: Tanya B. Dorff, Michael K.K. Wong, Joseph Clark, Gregory A. Daniels, Brendan D. Curti, Michael Morse, Howard Kaufman, David F. McDermott, David I. Quinn, Peter Zang, Nancy C. Gregory, Lisa Maria Eifler, Stephen Thomas, Marci White, Jatinder Singh, Janice P. Dutcher
Journal: Journal of Clinical Oncology (2018)

624 Background: High dose interleukin-2 (HD IL2) has traditionally been dosed every 8 hours for a maximum of 14 doses each cycle. We evaluated whether alternate dosing schedules and dose intensity affected achievement of complete response (CR) or partial response (PR) in the PROCLAIM registry. Methods: Patients with metastatic RCC were enrolled retrospectively and prospectively into the PROCLAIM registry to collect outcome data. Statistical methods for comparisons were done using Fisher’s and Chi Square tests. Results: From 2006-2017 the registry included 944 RCC patients; 257 (27%) women, 676 (72%) men. 844 (89%) were white. Histologic distribution: 624 (66%) clear cell, 93 (10%) medullary, 79 (8%) collecting duct, 78 (8%) chromophobe and 70 (7%) papillary. 207 (22%) had prior therapy with VEGF/mTOR. Best response was 51 (5.4%) CR and 169 (17.9%) PR; 263 (28%) progressive disease. 13 (1.4%) patients received q12 hour dosing while 830 (88%) received q8 hour dosing. 608 (64%) received 600 KIU/kg and 67 (7%) received 720 KIU/kg. Median # of doses in cycle 1 was 10 for CR and PR patients at 600 KIU/kg and 9 for those with stable or progressive disease. In the 720 KIU/kg group median #doses was 11 for CR, 8 for PR, and 7 for stable or progressive disease. In cycle 2 median doses received was 7.16 for patients with CR, 7.02 for PR and 6.76 for stable disease. Median dose intensity is similar at these two dose levels. Associations with achievement of CR/PR are summarized in the Table. Conclusions: There is no difference in response rate based on dosing schedule but the small number of subjects dosed q12 hours limits interpretation. Good performance patients possess the best opportunity for benefit from HD IL2. There is a trend for response with higher median # doses. Further studies of alternate dosing schedules are warranted. Clinical trial information: NCT01415167. [Table: see text]
Cognitive Outcomes of Children Born Extremely or Very Preterm Since the 1990s and Associated Risk Factors
Authors: E. Sabrina Twilhaar, Rebecca M. Wade, Jorrit F. de Kieviet, Johannes B. van Goudoever, Ruurd M. van Elburg, Jaap Oosterlaan
Journal: JAMA Pediatrics (2018)

Despite apparent progress in perinatal care, children born extremely or very preterm (EP/VP) remain at high risk for cognitive deficits. Insight into factors contributing to cognitive outcome is key to improve outcomes after EP/VP birth.