tbuckley/cabot-search huggingface dataset:
The problem with doctors
Authors: Mark Frame
Journal: BMJ (2006)

I'm a rather neurotic and distressed surgical trainee almost half way through a self constructed basic surgical training. I wasn't always like this. In fact, when I was at medical school in Aberdeen I felt quite competent and enthused with where I was going in medicine. I was going to be a surgeon. Getting there was easy I thought: junior house officer, senior house officer, registrar for five years, and then bingo, I would be my own boss. Lovely—a nice secure career. At university, no one wanted to explain in much detail—or perhaps we didn't want to listen, I'm not too sure. As junior house officers we were more concerned with having to spend a full day at work actually doing things and working out how we were going to spend all our new found wealth in the three days off we had every three weeks. I thought in the “there and now,” never thinking beyond the next six month job.

It all hit me when I started my first senior house officer job. It was as though reality had come up behind me …
Encoding third-person epistemic states contributes to episodic reconstruction of memories
Authors: Dora Kampis, András Keszei, Ildikó Király
Journal: Behavioral and Brain Sciences (2018)

Abstract We propose an extension to Mahr &amp; Csibra's (M&amp;C's) theory. For successful episodic memory formation, potentially relevant aspects of a situation need to be identified and encoded online and retained for prospective interactions . To be maximally convincing, the communicator not only has to encode not just any contextual detail, but also has to track information in relation to social partners.
18F-FDG PET/CT in Extranodal Burkitt Lymphoma
Authors: Pedro Jiménez Granero, Francisco Javier García Gómez, Marta Ruiz Mercado, Isabel Borrego Dorado
Journal: Clinical Nuclear Medicine (2015)

Burkitt lymphoma (BL) is a poorly differentiated non-Hodgkin B-cell lymphoma, more frequent in children than in adults. The extranodal debut of the disease is rare. We report a 43-year-old male patient with history of dyspnea. Burkitt lymphoma diagnosis was reached after biopsy of a pleural lesion. An initial staging F-FDG-PET/CT revealed large high-uptake lymphatic clusters in mediastinum, lung hilum, and extranodal involvement in pleura, pericardium, periphery of liver and spleen, all the omentum and peritoneum down to the pelvic floor, and bone marrow infiltration.
The Pattern of Mesenchymal Stem Cell Expression Is an Independent Marker of Outcome in Multiple Myeloma
Authors: Carolina Schinke, Pingping Qu, Syed J. Mehdi, Antje Hoering, Joshua Epstein, Sarah K. Johnson, Frits van Rhee, Maurizio Zangari, Sharmilan Thanendrarajan, Bart Barlogie, Faith E. Davies, Shmuel Yaccoby, Gareth J. Morgan
Journal: Clinical Cancer Research (2018)

Purpose: Mesenchymal stem cells (MSC) are an essential component of the bone marrow microenvironment and have shown to support cancer evolution in multiple myeloma. Despite the increasing evidence that multiple myeloma MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of this study was to determine the importance of MSCs in disease progression and outcome in multiple myeloma.Experimental Design: To determine the impact of MSCs on multiple myeloma outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in plasma cells (PC) or other cells present in bone marrow aspirates. We then applied this MSC gene signature to whole bone marrow biopsies of multiple myeloma patients compared with healthy controls and determined MSC expression scores specific to multiple myeloma and predictive of outcome.Results: We show that multiple myeloma MSC gene expression signatures can differentiate multiple myeloma from monoclonal gammopathy and smoldering multiple myeloma (SMM) as well as from healthy controls and treated multiple myeloma patients who have achieved a complete remission. We identified a prognostic gene score based on three MSC specific genes, COL4A1, NPR3 and ITGBL1, that was able to predict progression-free survival in multiple myeloma patients and progression into multiple myeloma from SMM.Conclusions: Our findings show that progression of multiple myeloma and of SMM into multiple myeloma does not rely solely on intrinsic PC factors, but is independently affected by the biology of the surrounding microenvironment. Clin Cancer Res; 24(12); 2913-9. ©2018 AACR.
UK graduates will not be guaranteed foundation training places, says UKFPO
Authors: Abi Rimmer
Journal: BMJ (2015)

UK graduates cannot expect to be guaranteed foundation training places in the future, the national director of the UK Foundation Programme Office has said.

Speaking at the BMA’s conference of staff, associate specialist, and specialty (SAS) doctors in London last week, Derek Gallen discussed plans outlined in the Shape of Training review to move the point of registration with the General Medical Council. He said that the report’s proposal to move the point of registration to the point of graduation from medical school was an attempt by David Greenaway, who carried out the review, to “tidy up” the current system.

“The original context that Greenaway’s report put it [in] was that he was trying to tidy up this anomaly which had the undergraduate universities in charge of the foundation …
Abstract 15243: Does Renal Haemodynamics Relate With Cardiac and Aortic Haemodynamics in the Early Stages of Essential Hypertension?
Authors: K. Kintis, Costas Tsioufis, E. Koutra, L. Nikolopoulou, A. Kasiakogias, I. Andrikou, I. Ioannidis, K. Filis, S. Patsilinakos, D. Tousoulis
Journal: Circulation (2015)

Introduction: The relationship of renal haemodynamics with cardiac and aortic hameodynamics is still unclear. Hypothesis: We evaluated the relationship of increased renal resistive index (RRI) with Augmentation index (AIx) and cardiac haemodynamics by means of mitral annular early diastolic velocity (E/Ea) in untreated patients with essential hypertension. Methods: 76 newly diagnosed untreated non diabetic patients with stage I-II essential hypertension [35 males, aged 50 years, office blood pressure (BP) = 143/ 91 mm Hg], underwent ABPM, complete echocardiographic study for determination of E/Ea and blood sampling for assessment of metabolic profile. Moreover, data on renal resistive index (RRI), obtained by Doppler ultrasound sampling of the intrarenal arteries, as well as augmentation index (AIx), were retrospectively analyzed. Results: Based on the mean value of RRI (0.60), hypertensives were classified into those with high and low RRI. Hypertensives with high RRI values compared to those with low values were older (55.6±9.8 vs 44.4±11.6 years, p &lt; 0.001), had lower 24-hour diastolic BP (77.5±7.7 vs 84.3±6.7 mmHg, p &lt; 0.001), lower 24-hour HR (71.2±10.3 vs 76.2±9.2 bpm, p &lt; 0.05), higher levels of AIx (27.2±8.2 vs 17.8±14.8 %, p &lt; 0.01), and higher values of E/Ea (lateral) (7.7±1.8 vs 6.2±2.3, p &lt; 0.05). In the total population, RRI was negatively related to 24-hour diastolic BP (r = -0.523, p &lt; 0.001) and 24-hour HR (r = -0.281, p &lt; 0.05), while it was positively associated with CRP (r = 0.335, p &lt; 0.05), TChol (r = 0.296, p &lt; 0.01), age (r = 0.443, r &lt; 0.001), AIx (r = 0.413, p = 0.001) and E/Ea(lateral) (r = 0.465, p &lt; 0.05). Multiple regression analysis revealed that 24-hour diastolic BP and E/Ea (lateral) were independent associated with RRI (R2 = 0.434, p &lt; 0.05). Conclusions: Increased vascular resistance of intrarenal arteries is associated with impaired aortic and cardiac haemodynamics, as reflected by increased AIx and E/Ea (lateral) values. RRI may be considered a useful surrogate of haemodynamics in essential hypertension.
S-TRAC trial: Sensitivity analyses of disease-free survival (DFS).
Authors: Daniel J. George, Allan J. Pantuck, Robert J. Motzer, Alain Ravaud, Bernard Escudier, Michael D. Staehler, Lucile Serfass, Sriram Krishnaswami, Michelle Casey, Mariajose Lechuga, Gary Koch, Robert A. Figlin
Journal: Journal of Clinical Oncology (2018)

633 Background: DFS has been frequently used as endpoint in the adjuvant setting and was the primary basis of approval for adjuvant cancer therapies. In S-TRAC, adjuvant sunitinib demonstrated a significant improvement of DFS vs. placebo in patients with locoregional renal cell carcinoma (RCC) based on blinded independent central review. DFS was defined as time from randomization until recurrence or death from any cause or second cancer. In the absence of a standard definition of DFS in RCC, multiple sensitivity analyses were performed to confirm the robustness of the DFS results from S-TRAC. Methods: Two analyses considered the time to recurrence including and excluding RCC specific deaths and contralateral kidney recurrence. Additional analyses used the same event and censoring rules as the primary analysis but considered earliest dates of relapse for equivocal new lesions later determined to be unequivocal -to align with RECIST 1.1 criteria for new lesions- and some alternative dates for secondary malignancies. Other sensitivity analyses evaluating alternative event and censoring rules as well as the imbalance in censoring in the first year in the primary analysis will also be presented. Results: The HR from select sensitivity analyses are presented in the Table. Conclusions: Results of sensitivity analyses with alternative definitions of DFS in S-TRAC demonstrated the robustness of the primary DFS analysis, with consistent HRs (0.76-0.81) favoring sunitinib. Clinical trial information: NCT00375674. [Table: see text]
MODIFIABLE FACTORS PREDICT MORTALITY AFTER PROLONGED CRITICAL ILLNESS FOLLOWING CONGENITAL HEART SURGERY
Authors: Aaron Dewitt, Joseph William Rossano, David K. Bailly, Priya Bhat, Nikhil Chanani, Brandon Kirkland, Michael-Alice Moga, Gabe Owens, Lauren Retzloff, Wenying Zhang, Mousumi Banerjee, Andrew Costarino, Geoffrey Bird, Sara Pasquali, Michael Gaies
Journal: Journal of the American College of Cardiology (2018)
OxyContin maker stops marketing opioids, as report details payments to advocacy groups
Authors: Owen Dyer
Journal: BMJ (2018)

Purdue Pharma, targeted in over 200 lawsuits for its role in the US opioid epidemic with fraudulent marketing of its semi-synthetic pill OxyContin, has cut its sales staff by half and said it would no longer market opioids to doctors. It will continue to make and sell them, however.

The remaining US sales staff of roughly 200 will instead be asked to promote non-opioid products, Purdue said. Enquiries from doctors about opioids will henceforth go to its medical affairs department.

“We are deeply troubled by the opioid crisis, and we are dedicated to being part of the solution,” the company said.

The policy change will not apply to Purdue’s subsidiary in Canada, although overdose deaths have also spiked there in recent years.

Purdue’s announcement came days …
Clinical significance of PD-L1 levels in plasma-derived exosomes in head and neck cancer.
Authors: Marie-Nicole Theodoraki, Sai Gopal Krishna Yerneni, Theresa Whiteside
Journal: Journal of Clinical Oncology (2018)

117 Background: Despite the broad spectrum of available therapies, HNSCC patients have poor outcome due to locoregional recurrence. Mechanisms responsible for immune suppression include activities of checkpoint receptors/ligands. HNSCCs with high expression levels of PD-L1 have especially poor outcome. Thus, PD-1 and PD-L1 inhibitors show potential as anticancer strategies. However, many patients with PD-L1+ HNSCC don’t benefit from checkpoint inhibitor therapy, suggesting that PDL-1 expression on tumors is not the only factor predictive of response. Tumor derived exosomes carry numerous immunosuppressive molecules and deliver them to recipient immune cells. We have demonstrated that elevated levels of circulating immunosuppressive exosomes play a key role in immune suppression and disease progression. Here, we show that surface PD-L1 on exosomes is responsible for these effects. Methods: Exosomes were isolated from plasma of 40 HNSCC patients by mini size exclusion chromatography, captured on beads using anti-CD63 Abs, stained for PD-1 and PD-L1 and analyzed by flow cytometry. Percentages of PD-L1+ and PD-1+ exosome/bead complexes were correlated with clinicopathological data. PD-L1 high or PD-L1 low exosomes were incubated with activated human CD8 T-cells ± PD-1 inhibitor and CD69 expression levels on T-cells were measured. Patients’ plasma was tested for soluble PD-L1 by ELISA. Results: The PD-L1 surface expression on exosomes correlated with patient’s disease activity, UICC stage and lymph node status with p values ranging from 0.0008-0.013. In contrast, plasma PD-L1 levels didn't correlate with any parameters. Exosome PD-1 levels were not informative. T-cell activation was inhibited (p &lt; 0.03) by co-incubation with PD-L1 high but not PD-L1 low exosomes. This inhibition was reversed by adding a PD-1 inhibitor to T-cells prior to their incubation with exosomes. Conclusions: We show that PD-L1 levels on exosomes, but not plasma levels, correlated with clinicopathological data in HNSCC patients. Blocking of PD-L1+ exosomes signaling to PD-1+ T-cells with anti-PD-1 Ab attenuated immune suppression. Altogether, PD-L1+ exosomes serve as useful metrics of disease and immune activity in HNSCC patients.
Protein <i>S</i> -Nitrosylation Controls Glycogen Synthase Kinase 3β Function Independent of Its Phosphorylation State
Authors: Sheng-Bing Wang, Vidya Venkatraman, Erin L. Crowgey, Ting Liu, Zongming Fu, Ronald Holewinski, Mark Ranek, David A. Kass, Brian O’Rourke, Jennifer E. Van Eyk
Journal: Circulation Research (2018)

Rationale: GSK-3β (glycogen synthase kinase 3β) is a multifunctional and constitutively active kinase known to regulate a myriad of cellular processes. The primary mechanism to regulate its function is through phosphorylation-dependent inhibition at serine-9 residue. Emerging evidence indicates that there may be alternative mechanisms that control GSK-3β for certain functions. Objectives: Here, we sought to understand the role of protein S -nitrosylation (SNO) on the function of GSK-3β. SNO-dependent modulation of the localization of GSK-3β and its ability to phosphorylate downstream targets was investigated in vitro, and the network of proteins differentially impacted by phospho- or SNO-dependent GSK-3β regulation and in vivo SNO modification of key signaling kinases during the development of heart failure was also studied. Methods and Results: We found that GSK-3β undergoes site-specific SNO both in vitro, in HEK293 cells, H9C2 myoblasts, and primary neonatal rat ventricular myocytes, as well as in vivo, in hearts from an animal model of heart failure and sudden cardiac death. S -nitrosylation of GSK-3β significantly inhibits its kinase activity independent of the canonical phospho-inhibition pathway. S -nitrosylation of GSK-3β promotes its nuclear translocation and access to novel downstream phosphosubstrates which are enriched for a novel amino acid consensus sequence motif. Quantitative phosphoproteomics pathway analysis reveals that nuclear GSK-3β plays a central role in cell cycle control, RNA splicing, and DNA damage response. Conclusions: The results indicate that SNO has a differential effect on the location and activity of GSK-3β in the cytoplasm versus the nucleus. SNO modification of GSK-3β occurs in vivo and could contribute to the pathobiology of heart failure and sudden cardiac death.
Development of a novel albumin-based and maleimidopropionic acid-conjugated peptide with prolonged half-life and increased <i>in vivo</i> anti-tumor efficacy
Authors: Junnan Feng, Chuanke Zhao, Lixin Wang, Like Qu, Hua Zhu, Zhi Yang, Guo An, Huifang Tian, Chengchao Shou
Journal: Theranostics (2018)

Angiogenesis plays a critical role in tumor aggressiveness, and a lot of anti-angiogenic agents have been used in clinical therapy. The therapeutic efficacy of peptides are generally restricted by the short in vivo life-time, thus, we were interested in developing a novel albumin-based and maleimidopropionic acid-conjugated peptide to prolong the half-life and improve the anti-tumor effect. Methods: We developed a peptide F56 with a maleimidopropionic acid (MPA) at the C-terminal (denoted as F56-CM), which allows immediate and irreversible conjugation with serum albumin. Biological property and anti-tumor activity of F56-CM were evaluated in vitro and in vivo. Results: We showed that F56-CM reduced migration and tube formation of endothelial cells in vitro and inhibited the generation of subintestinal vessels (SIV) in zebrafish embryos in vivo. F56-CM inhibited vascular endothelial growth factor (VEGF) induced phosphorylation of VEGFR1 and activation of the PI3K-AKT axis. Furthermore, F56-CM rapidly conjugated with albumin upon intravenous injection and extended the biological half-life of F56 from 0.4249 h to 6.967 h in rats. Compared with F56, F56-CM exhibited stronger anti-tumor activity on both BGC-823 gastric cancer and HT-29 colon cancer xenografts in nude mice, and the statistical difference was remarkable. More significantly, the efficacy of F56-CM inhibiting lung metastasis of BGC-823 cells was also better than that of F56. The inhibition rates were 62.1% and 78.9% for F56 and F56-CM respectively when administrated every day, and 43.8% and 63.1% when administrated every four days at equal dose. Conclusions: Taken together, our results demonstrated that F56-CM has considerable potential for cancer therapy.
I passed the Professional and Linguistic Assessment Board's exam in January 2004 and have since done clinical attachments: a month in four specialties. I would like to become a GP. I took four years out to bring up children. I am still looking for a job in the NHS. Which foundation year should I apply for?
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>
Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multi parametric
Authors: Vijay Sawlani, Robert Flintham, Nigel Davies, Charles Fong, Sara Meade, Andrew Peet, Garth Cruickshank, Helen Benghiat, Paul Sanghera
Journal: Neuro-Oncology (2018)

PurposeConventional MRI methods are insufficient to accurately differentiate between local tumour recurrence and radiation-induced necrosis. Advanced MRI techniques such as perfusion imaging, diffusion imaging and spectroscopy have individually been shown to aid the assessment of response following SRS treatment of brain metastases [1–3]. However, the potential added-value of a multi-parametric approach using a combination of these techniques has not been investigated. Materials and MethodsA retrospective analysis was performed on 10 multi-parametric MRI examinations following SRS for metastatic brain lesions in a cohort of 7 patients with varying primary malignant diseases (melanoma, n=3; breast, n=3; small cell lung, n=1). Multi-parametric MRI examination consisted of dynamic susceptibility contrast (DSC) perfusion imaging, diffusion weighted imaging (DWI) and both single- and multi-voxel MR spectroscopy (MRS) (TE = 30 ms). Relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) maps were calculated from DSC and DWI data respectively using Siemens Syngo software and an rCBV ratio (lesion: contralateral) calculated. Analysis of MRS was performed using TARQUIN [4]. Correlations between rCBV ratio, ADC and Cho:Cr were investigated. Predictions of response based on each parameter were tested using radiological and clinical follow up. ResultsCho:Cr demonstrates a strong positive correlation with rCBV ratio (r = 0.89, p < 0.01). This is in agreement with previous work in pre-treatment metastases [5]. No significant correlations were observed between ADC and rCBV or Cho:Cr. Applying a reported threshold for rCBV ratio of 2.1 [1], patients were divided into two groups showing suspected tumour recurrence (n=4) and suspected radiation necrosis (n=3). ConclusionPreliminary results suggest that a combination of high rCBV, low ADC and high Cho: Cr can clearly identify local tumour recurrence and that multi-parametric MRI may show improved accuracy compared with any of the techniques in isolation.
I want to know if a doctor from Iran can apply to be a doctor in England, and if so what they need to do in order to come over here and work as a doctor?
Authors: Anne Hastie
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>
Decadal Changes in the Edible Supply of Seafood and Methylmercury Exposure in the United States
Authors: Elsie M. Sunderland, Miling Li, Kurt Bullard
Journal: Environmental Health Perspectives (2018)

Methylmercury (MeHg) exposure is associated with adverse effects on neurodevelopment and cardiovascular health. Previous work indicates most MeHg is from marine fish sold in the commercial market, but does not fully resolve supply regions globally. This information is critical for linking changes in environmental MeHg levels to human exposure in the U.S. population.We used available data to estimate the geographic origins of seafood consumed in the United States (major ocean basins, coastal fisheries, aquaculture, freshwater) and how shifts in edible supply affected MeHg exposures between 2000-2002 and 2010-2012.Source regions for edible seafood and MeHg exposure in the United States were characterized from national and international landing, export and import data from the Food and Agricultural Organization of the United Nations and the U.S. National Marine Fisheries Service.Our analysis suggests 37% of U.S. population-wide MeHg exposure is from mainly domestic coastal systems and 45% from open ocean ecosystems. We estimate that the Pacific Ocean alone supplies more than half of total MeHg exposure. Aquaculture and freshwater fisheries together account for an estimated 18% of total MeHg intake. Shifts in seafood types and supply regions between 2000-2002 and 2010-2012 reflect changes in consumer preferences (e.g., away from canned light meat tuna), global ecosystem shifts (e.g., northern migration of cod stocks), and increasing supply from aquaculture (e.g., shrimp and salmon).Our findings indicate global actions that reduce anthropogenic Hg emissions will be beneficial for U.S. seafood consumers because open ocean ecosystems supply a large fraction of their MeHg exposure. However, our estimates suggest that domestic actions can provide the greatest benefit for coastal seafood consumers. https://doi.org/10.1289/EHP2644.