tbuckley/cabot-search huggingface dataset:
Postgraduate diploma in burn care
Authors: Talal Al-Jabri
Journal: BMJ (2011)

The two year programme aims to provide a core curriculum for established surgeons, surgical trainees, and physicians who wish to practise in the field of burn care after completing specialist training. Although primarily aimed at people working in plastic surgery units, it is invaluable to emergency medicine specialists and other specialists who encounter burn injuries in clinical practice. This year delegates have come from Ireland, Manchester, and London, and students in the Middle East are taking part online.

Entry requirements for the course are the MBBS or equivalent. I started the course in 2009 while working as a senior house officer in emergency medicine. I am now a core surgical trainee in plastic surgery, which has made the diploma much more relevant to my clinical practice.

The course fee …
Editor’s Choice: Difficult decisions
Authors: Abi Rimmer
Journal: BMJ (2015)

Choosing which specialty to enter can be a hard decision for junior doctors, with numerous options available to them in a range of fields. Having made that decision, choosing a subspecialty can come with its own challenges, as Kathy Oxtoby explores this week (http://careers.bmj.com/careers/advice/view-article.html?id=20021705). 

As with choosing a specialty, doctors are advised, when selecting an area in which to subspecialise, to consider …
Communicating with colleagues
Authors: Mark Griffiths
Journal: BMJ (2005)

Cater for your audience —When imparting information to a group of colleagues, try to find out beforehand what they want to know. Do they want information in the form of regular emails or do they want to be told during a talk or meeting?

Get people on your side —If you are leading a particular initiative, it is a good idea to get a few …
Deletion of IRF8 (Interferon Regulatory Factor 8)-Dependent Dendritic Cells Abrogates Proatherogenic Adaptive Immunity
Authors: Marc Clément, Yacine Haddad, Juliette Raffort, Fabien Lareyre, Stephen A. Newland, Leanne Master, James Harrison, Maria Ozsvar-Kozma, Patrick Bruneval, Christoph J. Binder, Soraya Taleb, Ziad Mallat
Journal: Circulation Research (2018)

Rationale: Despite an established role for adaptive immune responses in atherosclerosis, the contribution of dendritic cells (DCs) and their various subsets is still poorly understood. Objective: Here, we address the role of IRF8 (interferon regulatory factor 8)-dependent DCs (lymphoid CD8α + and their developmentally related nonlymphoid CD103 + DCs) in the induction of proatherogenic immune responses during high fat feeding. Methods and Results: Using a fate-mapping technique to track DCs originating from a DNGR1 + (dendritic cell natural killer lectin group receptor 1) precursor ( Clec9a +/cre Rosa +/EYFP mice), we first show that YFP hi CD11c hi MHCII hi (major histocompatibility complex class II) DCs are present in the atherosclerotic aorta of low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice and are CD11b – CD103 + IRF8 hi . Restricted deletion of IRF8 in DCs ( Irf8 flox/flox Cd11c Cre ) reduces the accumulation of CD11c hi MHCII hi DCs in the aorta without affecting CD11b + CD103 – DCs or macrophages but completely abolishes the accumulation of aortic CD11b – CD103 + DCs. Lymphoid CD8α + DCs are also deleted. This is associated with a significant reduction of aortic T-cell accumulation and a marked reduction of high-fat diet–induced systemic T-cell priming, activation, and differentiation toward T helper type 1 cells, T follicular helper cells, and regulatory T cells. As a consequence, B-cell activation and germinal center responses to high-fat diet are also markedly reduced. IRF8 deletion in DCs significantly reduces the development of atherosclerosis, predominantly in the aortic sinus, despite a modest increase in total plasma cholesterol levels. Conclusions: IRF8 expression in DCs plays a nonredundant role in the development of proatherogenic adaptive immunity.
Abstract P3-10-04: Obesity and adipose inflammation in men with breast cancer
Authors: S Williams, JC Parrish, XK Zhou, H Wang, A Dierickx, A Gucalp, AJ Dannenberg, NM Iyengar
Journal: Cancer Research (2018)

Abstract Background: Elevated body mass index (BMI) is associated with increased risk of hormone receptor (HR)-positive breast cancer in postmenopausal women and worsened outcomes after breast cancer diagnosis. These observations may be partly attributable to adipose inflammation, which is prevalent in the breasts of obese women and is associated with worsened breast cancer survival. In men, some studies have reported obesity to be a risk factor for breast cancer, however the biologic links are not well characterized. Whether adipose inflammation occurs in male breast tissue has not been previously reported. Here we examined the relationships among pre-diagnosis BMI, adipose inflammation, and breast cancer features in men. Methods: Males diagnosed with stage 0 – III breast cancer who underwent mastectomy at Memorial Sloan Kettering (MSK) between August 1991 – November 2011 were included in this retrospective cohort study. Pre-operative BMI was categorized as normal or underweight (&amp;lt;25), overweight (25 – 29.9), obese (≥30), or morbidly obese (≥40 or ≥35 + co-morbidity). Archived breast tissue was subjected to CD68 immunohistochemistry to detect adipose inflammation, defined by the presence of dead or dying adipocytes surrounded by macrophages – known as crown-like structures of the breast (CLS-B). Clinicopathologic associations with BMI and CLS-B were analyzed by logistic regression and Fisher's exact test. Results: A total of 141 men were included; median age 63 (range 23 – 96). By BMI category, 25 were normal or underweight, 65 overweight, and 51 obese – of which 19 were morbidly obese. Only 11 men had known BRCA1/2 mutations. Median age at diagnosis was 69 in normal/underweight men versus 63 in obese men and 51 in morbidly obese men (P≤0.05). Among those with invasive tumors, average tumor size was 1.50 cm (± 0.84) in normal/underweight men versus 2.04 (±0.81) in morbidly obese men (P≤0.05). Archived breast tissue was available from 92 (65%) men. Breast adipose inflammation was present in 55 (60%) men, and average BMI was 31 (±8) versus 28 (±5) in men with versus without inflammation, respectively (P=0.07). Conclusions: Obesity is associated with early onset breast cancer in men. Morbidly obese men were diagnosed with breast cancer at an even younger age and had larger tumors than normal weight individuals. These findings support further studies to investigate mechanisms, such as adipose inflammation, through which obesity may promote breast cancer in men. Citation Format: Williams S, Parrish JC, Zhou XK, Wang H, Dierickx A, Gucalp A, Dannenberg AJ, Iyengar NM. Obesity and adipose inflammation in men with breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-04.
Abstract 18666: A Carbon Monoxide (CO) Scavenging Agent Reverses CO-Induced Mitochondrial Inhibition in vitro and in vivo
Authors: Jason J Rose, Ling Wang, Ivan Azarov, Qinzi Xu, Xueyin N Huang, Andrea Belanger, Ying Wang, Lanping Guo, Chen Lui, Kamil B Ucer, Charles F McTiernan, Christopher P O’Donnell, Jesús Tejero, Daniel B Kim-Shapiro, Sruti Shiva, Mark T Gladwin
Journal: Circulation (2016)

Introduction: There are 50,000 cases of carbon monoxide (CO) poisoning per year in the United States alone. Even with current therapy, 1/3 of moderate-severely poisoned patients have cardiac dysfun...
Checklist for would be doctors aims to improve access to profession
Authors: Caroline White
Journal: BMJ (2013)

A checklist of essential qualities for would be doctors will be drawn up by the Medical Schools Council to help remove inconsistencies in admission and selection processes and to improve access to the medical profession for applicants from diverse social backgrounds.

The decision was taken on 26 November at a symposium of admissions deans, convened in London by the Selecting for Excellence Group, which was set up earlier in the year under the aegis of the Medical Schools Council.1 The group aims to widen participation in medicine and ensure that the best candidates can apply, irrespective of their social background. …
Genes involved in prostate cancer progression determine MRI visibility
Authors: Ping Li, Sungyong You, Christopher Nguyen, Yanping Wang, Jayoung Kim, Deepika Sirohi, Asha Ziembiec, Daniel Luthringer, Shih-Chieh Lin, Timothy Daskivich, Jonathan Wu, Michael R Freeman, Rola Saouaf, Debiao Li, Hyung L. Kim
Journal: Theranostics (2018)

MRI is used to image prostate cancer and target tumors for biopsy or therapeutic ablation. The objective was to understand the biology of tumors not visible on MRI that may go undiagnosed and untreated. Methods: Prostate cancers visible or invisible on multiparametric MRI were macrodissected and examined by RNAseq. Differentially expressed genes (DEGs) based on MRI visibility status were cross-referenced with publicly available gene expression databases to identify genes associated with disease progression. Genes with potential roles in determining MRI visibility and disease progression were knocked down in murine prostate cancer xenografts, and imaged by MRI. Results: RNAseq identified 1,654 DEGs based on MRI visibility status. Comparison of DEGs based on MRI visibility and tumor characteristics revealed that Gleason score (dissimilarity test, p<0.0001) and tumor size (dissimilarity test, p<0.039) did not completely determine MRI visibility. Genes in previously reported prognostic signatures significantly correlated with MRI visibility suggesting that MRI visibility was prognostic. Cross-referencing DEGs with external datasets identified four genes (PHYHD1, CENPF, ALDH2, GDF15) that predict MRI visibility, progression free survival and metastatic deposits. Genetic modification of a human prostate cancer cell line to induce miR-101 and suppress CENPF decreased cell migration and invasion. As prostate cancer xenografts in mice, these cells had decreased visibility on diffusion weighted MRI and decreased perfusion, which correlated with immunostaining showing decreased cell density and proliferation. Conclusions: Genes involved in prostate cancer prognosis and metastasis determine MRI visibility, indicating that MRI visibility has prognostic significance. MRI visibility was associated with genetic features linked to poor prognosis.
Liver Transplantation for Intermediate-Stage Hepatocellular Carcinoma
Authors: Naoko Kamo, Toshimi Kaido, Shintaro Yagi, Hideaki Okajima, Shinji Uemoto
Journal: Liver Cancer (2018)

Transarterial chemoembolization is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer staging system. However, in Japan, not a few patients with intermediate-stage HCC undergo liver transplantation (LT). The present study investigated characteristics and outcomes of LT for intermediate-stage HCC. Between February 1999 and November 2016, a total of 226 patients underwent LT for HCC at our institute. Among these, 56 patients showed intermediate-stage HCC (24.8%). We examined overall survival and recurrence rate after LT according to our extended criteria (maximum size ≤5 cm, number ≤10, des-gamma-carboxy prothrombin ≤400 mAU/mL) and pretreatment. One-, 3-, and 5-year overall survival and recurrence rates of LT for intermediate-stage HCC were 88/64/58% and 22/34/44%, respectively. One-, 3-, and 5-year overall survival and recurrence rates in patients within (n = 35) the criteria (94/80/80% and 9/15/22%, respectively) were significantly better than those in patients beyond (n = 21) the criteria (81/43/29%, p = 0.002 and 39/41/66%, p = 0.001, respectively). Forty-nine cases (88%) had a history of pretreatment. In patients within our extended criteria, overall survival and recurrence rates did not differ significantly between patients with (n = 31) and without (n = 4) pretreatment. In conclusion, outcomes after LT for intermediate-stage HCC are more favorable if patients meet our extended criteria.
Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial
Authors: Joseph M Unger, Dawn L Hershman, Cathee Till, Catherine M Tangen, William E Barlow, Scott D Ramsey, Phyllis J Goodman, Ian M Thompson
Journal: JNCI Journal of the National Cancer Institute (2018)

Investigators have used administrative claims to better understand cancer outcomes when a research question cannot feasibly be examined within a study. The Prostate Cancer Prevention Trial (PCPT) showed that seven years of finasteride reduced prostate cancer (PC) risk by 25% in men age 55 years or older. However, it was unclear whether the observed reduction in PC for finasteride participants would be maintained after finasteride discontinuation.We examined PC diagnoses identified by PCPT study records and Medicare claims (finasteride = 9423, placebo = 9457). A Medicare-defined PC diagnosis algorithm was defined using diagnosis and procedure codes. Multivariable Cox regression was used to examine time to PC within prespecified follow-up windows (<6.5, 6.5-7.5, and >7.5 years) using time-dependent covariates interacting with intervention assignment to account for the PCPT protocol-specified end-of-study biopsy at seven years. All statistical tests were two-sided.Median follow-up using the linked database was 16 years. Overall, finasteride arm participants had a 21.1% decrease in the hazard ratio of PC (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.74 to 0.84, P < .001). The beneficial effect of finasteride in reducing the hazard ratio of PC was most pronounced in the first 7.5 years (HR = 0.71, 95% CI = 0.66 to 0.77, P < .001), consistent with the original study findings; after 7.5 years, there was no increased risk of PC for finasteride arm participants (HR = 1.10, 95% CI = 0.96 to 1.26, P = .18).Finasteride provides a substantial reduction in PC through 16 years of follow-up. There was no strong evidence that the benefit of finasteride diminished after the end-of-study follow-up. Utilizing Medicare claims to augment PCPT follow-up illustrates how the novel use of secondary data sources can enhance the ability to detect long-term outcomes from prospective studies.
I am a GMC registered overseas doctor. I have applied for over 300 SHO posts and have not been shortlisted once. I have emailed over 400 consultants asking for a clinical attachment, with no luck. My curriculum vitae is perfect—please advise.
Authors: Faisal Hanif
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.
Emergency medicine doctors should have “fair equality of leisure time” to compensate for unsociable hours, College of Emergency Medicine says
Authors: Tom Moberly
Journal: BMJ (2015)

Doctors working in emergency medicine should have a “fair equality of leisure and family time” to compensate for night, evening, and weekend work, the College of Emergency Medicine has said.

Speaking at the college’s conference earlier this month, Kevin Reynard, its vice president of the college, said that efforts to boost the total number of doctors working in the specialty needed to focus on retention. “It is clear that the issue isn’t about recruiting people into the specialty,” he said. “The issue is about retaining them once they get there.”

Reynard said that developing “equitable terms and conditions” would be key to this. “This isn’t just going to happen by crossing our fingers and hoping,” he said. “We need to change the way we work and the conditions that people work in so we don’t drive people away.”

He said that the organisations that would need to be involved in implementing such developments already acknowledged that changes had to …
I want to do a management course and work in NHS management. (I am a post-FRCA year 2 specialist registrar.) Please advise
Authors: Peter Maguire
Journal: BMJ (2004)

We tested the popular, unproven theory that tinnitus is caused by resetting of auditory predictions toward a persistent low-intensity sound. Electroencephalographic mismatch negativity responses, which quantify the violation of sensory predictions, to unattended tinnitus-like sounds were greater in response to upward than downward intensity deviants in 26 unselected chronic tinnitus subjects with normal to severely impaired hearing, and in 15 acute tinnitus subjects, but not in 26 hearing and age-matched controls (<i>p</i> &lt; 0.001, receiver operator characteristic, area under the curve, 0.77), or in 20 healthy and hearing-impaired controls presented with simulated tinnitus. The findings support a prediction resetting model of tinnitus generation, and may form the basis of a convenient tinnitus biomarker, which we name Intensity Mismatch Asymmetry, which is usable across species, is quick and tolerable, and requires no training. <b>SIGNIFICANCE STATEMENT</b> In current models, perception is based around the generation of internal predictions of the environment, which are tested and updated using evidence from the senses. Here, we test the theory that auditory phantom perception (tinnitus) occurs when a default auditory prediction is formed to explain spontaneous activity in the subcortical pathway, rather than ignoring it as noise. We find that chronic tinnitus patients show an abnormal pattern of evoked responses to unexpectedly loud and quiet sounds that both supports this hypothesis and provides fairly accurate classification of tinnitus status at the individual subject level. This approach to objectively demonstrating the predictions underlying pathological perceptual states may also have a much wider utility, for instance, in chronic pain.
Abstract ES2-1: The pathology of high risk proliferative lesions of the breast
Authors: KP Siziopikou
Journal: Cancer Research (2018)

Abstract A number of breast lesions diagnosed by pathologic examination of breast tissue are known to confer an increased risk for future development of breast cancer. Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are lesions conferring a moderately increased risk of 4-5x over baseline. Lobular carcinoma in situ (LCIS) and variants confer a markedly increased risk of 8-10x over the baseline. The magnitude of the risk, the effect of the patient's age and family history, the laterality of the future malignancy and the type of subsequent cancer development are different between all these high risk proliferative breast lesions. In addition, the spectrum of columnar cell lesions of the breast are thought to represent an early non-obligate precursor in the development of the low grade neoplasia of the breast. Of interest, many of these lesions share common genetic abnormalities that are different than those seen in high grade in situ and invasive carcinomas of the breast. These observations have implications for our current understanding of the breast cancer progression model and our recommendations for the therapeutic management of patients with high risk proliferative lesions of the breast. Citation Format: Siziopikou KP. The pathology of high risk proliferative lesions of the breast [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 ES2-1.
Menopausal special skills course
Authors: Sreekala Seepana
Journal: BMJ (2008)

A woman’s average life expectancy at birth in the United Kingdom is currently 81 years; it is increasing and is estimated to reach 85 years by 2031. British women can expect over 30 years of postmenopausal life, and because more women will reach the age of 100, the menopause can now be considered to be a mid-life event. 

A substantial proportion of women worldwide suffer menopausal symptoms. Few seek help, most suffering in silence. Of those who do seek help, many do not get the appropriate treatment as there is considerable uncertainty among the medical profession about the management of the menopause, especially with fears of breast cancer, stroke, …
Drug Interactions With Non–Vitamin K Oral Anticoagulants
Authors: Anne-Laure Sennesael, Séverine Henrard, Anne Spinewine
Journal: JAMA (2018)

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