tbuckley/cabot-search huggingface dataset:
Bristol echo course for neonatologists
Authors: Roopali Soni
Journal: BMJ (2012)

The course is for neonatologists and paediatricians who want to gain basic echo skills and learn about important aspects of congenital heart disease.

It takes place over two days, and the emphasis is on encouraging participants to get as much hands-on experience as possible.

The first day starts with lectures on the basic physics of ultrasonography and echocardiography, on cardiac anatomy, and on the approach to echo in the newborn, including the standard views. The second half of the day includes two hands-on sessions in which participants are encouraged to scan children in small …
Predicting oral disintegrating tablet formulations by neural network techniques
Authors: Run Han, Yilong Yang, Xiaoshan Li, Defang Ouyang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Oral Disintegrating Tablets (ODTs) is a novel dosage form that can be dissolved on the tongue within 3min or less especially for geriatric and pediatric patients. Current ODT formulation studies usually rely on the personal experience of pharmaceutical experts and trial-and-error in the laboratory, which is inefficient and time-consuming. The aim of current research was to establish the prediction model of ODT formulations with direct compression process by Artificial Neural Network (ANN) and Deep Neural Network (DNN) techniques. 145 formulation data were extracted from Web of Science. All data sets were divided into three parts: training set (105 data), validation set (20) and testing set (20). ANN and DNN were compared for the prediction of the disintegrating time. The accuracy of the ANN model has reached 85.60%, 80.00% and 75.00% on the training set, validation set and testing set respectively, whereas that of the DNN model was 85.60%, 85.00% and 80.00%, respectively. Compared with the ANN, DNN showed the better prediction for ODT formulations. It is the first time that deep neural network with the improved dataset selection algorithm is applied to formulation prediction on small data. The proposed predictive approach could evaluate the critical parameters about quality control of formulation, and guide research and process development. The implementation of this prediction model could effectively reduce drug product development timeline and material usage, and proactively facilitate the development of a robust drug product.
The gender pay gap: female doctors still earn a third less than male doctors
Authors: Abi Rimmer
Journal: BMJ (2017)

Across all employment sectors in the UK, female workers earn less than their male counterparts. This gender pay gap has continued despite repeated efforts to tackle the underlying factors.

In medicine, even though nationally agreed salary scales should eliminate the effects of individuals negotiating their own pay, the pay gap is wider than in other professions and employment sectors. Data from the Office for National Statistics …
Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications
Authors: Josef R. Bober, Chase L. Beisel, Nikhil U. Nair
Journal: Annual Review of Biomedical Engineering (2018)

An increasing number of studies have strongly correlated the composition of the human microbiota with many human health conditions and, in several cases, have shown that manipulating the microbiota directly affects health. These insights have generated significant interest in engineering indigenous microbiota community members and nonresident probiotic bacteria as biotic diagnostics and therapeutics that can probe and improve human health. In this review, we discuss recent advances in synthetic biology to engineer commensal and probiotic lactic acid bacteria, bifidobacteria, and Bacteroides for these purposes, and we provide our perspective on the future potential of these technologies.
A phase 1/2a trial of docetaxel plus ribavirin for reprogramming efficacy in patients with progressive metastatic castration resistant prostate cancer who have previously received docetaxel alone: DRREEM trial.
Authors: Takeo Kosaka, Toshiaki Shinojima, Kayoko Kikuchi, Sachiko Hagiwara, Shin-ichiro Kojima, Hiroshi Hongo, Koji Ueda, Shinji Miyake, Mototsugu Oya
Journal: Journal of Clinical Oncology (2018)

329 Background: We previously reported a novel cell reprogramming approach, termed drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting the cancer stemness-related gene network, and identified ribavirin as a candidate drug for overcoming docetaxel-resistant castration-resistant prostate cancer (CRPC). We conducted this phase 1/2a trial of docetaxel plus ribavirin for reprogramming efficacy in patients with progressive metastatic castration resistant prostate cancer who have previously received docetaxel alone. (DRREEM trial) Methods: In this clinical study, patients received intravenous docetaxel at 60-75 mg/m 2 is intravenously administered on Cycle1-Day1 in combination with the investigational drug (ribavirin). Docetaxel is administered at 3-week intervals (1 cycle) (total: 3 cycles). During administration, the dose may be reduced based on the subject’s condition if necessary. The primary endpoint was safety. Accessory evaluation items included prostate-specific antigen (PSA) response, objective response rate, health-related quality of lifel. Exploratory items included changes in CTC count, cfDNA, and exosome. Patients with progressive CRPC based on PSA and/or radiographic criteria, performance status (PS) 0–1, and normal renal and hepatic function were eligible. Results: Six patients were enrolled in this study; average age was 71.7±4.2. Average serum PSA concentration was 100.1±128.0 ng/ml (range: 3.0-336.8). The median cycle of docetaxel received before the study was 6 cycles. Safety: Grade 3/4 adverse events requiring dose modification were not observed. Two patients showed PSA reduction. Three patients showed stable disease. Changes in the blood concentrations of ribavirin, docetaxel, and prednisolone were within normal range. Conclusions: This combination of ribavirin with docetaxel was well tolerated with a promising response rate that justifies further investigations in docetaxel-resistant CRPC. This clinical study provides a useful drug re-positioning model in the area of translational medicine. Clinical trial information: UMIN000021107.
CYP2C19 STATUS AND OUTCOMES IN THE EUCLID TRIAL
Authors: Manesh R. Patel, Gretchen Heizer, Kenneth Mahaffey, F. Gerry Fowkes, Jeffrey Berger, Iris Baumgartner, Frank Rockhold, Peter Held, Brian Katona, Lars Norgren, William Jones, Juuso Blomster, William Hiatt
Journal: Journal of the American College of Cardiology (2018)
Abstract P5-01-02: Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results
Authors: GM Rauch, BE Adrada, C Kappadath, RP Candelaria, ML Huang, L Santiago, T Moseley, ME Scoggins, JD Knudtson, BP Lopez, KR Hess, S Krishnamurthy, S Moulder, V Valero, W Yang
Journal: Cancer Research (2018)

Abstract Purpose: To report preliminary data in a pilot study evaluating the ability of Tc99m sestamibi Molecular Breast Imaging (MBI) to predict response and assess residual disease at the completion of neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: Patients with localized, invasive breast cancer (T1-T4, N0-N3, M0) planned for NAC were enrolled in this prospective IRB approved clinical trial. All patients had digital mammography (DM), ultrasound (US), and MBI at baseline (T0), after 2 NAC cycles (T1), and at after NAC completion (T2). Tumor size and volume changes were compared with residual disease at surgery. MBI images were corrected for scatter and attenuation using a novel approach and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: tumor to background ratio (TBR), fractional activity uptake (FAU), and MBI-specific standardized uptake value (SUV). ROC analysis was performed. Results: Patients (n=25) who completed NAC, had 75 imaging time points and had surgery, were included in this analysis. Median age was 49 years (range 31 -77). Eleven patients (11/25, 44%) had complete pathologic response (pCR). Absolute TBR values after 2 cycles (T1) and before surgery (T2) had highest correlation with pCR (AUC 0.81; 95% CI 0.63 to 0.99, p=0.01, and AUC 0.78; 95% CI 0.59 to 0.97, p=0.015, respectively). Change in SUV after 2 cycles, Δ SUV1 (T1-T0), (AUC 0.84; 95% CI 0.66 to 1.00, p=0.01) and change in SUV prior to surgery, Δ SUV2 (T2-T0) (AUC 0.80; 95% CI 0.60 to 1.00, p=0.02), were most predictive of pCR. Tumor size and volume showed modest specificity for detecting residual disease, and was highest for MBI (79%), followed by MMG (64%), and lowest for US (55%). Conclusion: Quantitative MBI metrics show promise for the prediction of pCR in breast cancer patients undergoing NAC. Establishment of quantitative metrics for the early prediction of tumor response during NAC of breast cancer patients may provide an alternate to influencing NAC choice early in the management algorithm. Further investigation with a larger sample size is warranted. Citation Format: Rauch GM, Adrada BE, Kappadath C, Candelaria RP, Huang ML, Santiago L, Moseley T, Scoggins ME, Knudtson JD, Lopez BP, Hess KR, Krishnamurthy S, Moulder S, Valero V, Yang W. Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results [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 P5-01-02.
No evidence that employing management consultants improves efficiency in NHS
Authors: Matthew Limb
Journal: BMJ (2018)

NHS trusts have spent millions of pounds on external management consultants which has led to a “significant” rise in inefficiency, ultimately worsening services, an analysis has found.1

The study linked spending on management consultants by 120 English trusts with measures of organisational efficiency, and found that only a minority experienced efficiency gains. It was carried out by academics at the universities of Bristol, Seville, and Warwick Business School and published in the journal Policy and Politics. 

The trusts spent around £600m (€679m; $836m) in total on management consultants from 2009 to 10 to 2012-13. Researchers compared the expenditure against the reference costs index (RCI) used to measure the efficiency of NHS providers and to …
Psychiatry in the Caribbean
Authors: Cyrus Abbasian
Journal: BMJ (2004)

During my holiday in the Cayman Islands in autumn 2003 I visited the local mental health unit in Grand Cayman, the largest of the three Cayman Islands, which are located in the western Caribbean. Having done most of my training in inner London, I was curious to find out more about psychiatric practice in the Caribbean. This seemed the perfect opportunity, and I was not disappointed.

Grand Cayman has two hospitals, each with one resident psychiatrist. I visited the main Cayman Islands' health services complex. The psychiatric ward is an eight bedded unit situated on site and was opened only a few months before my visit. It caters for patients from adolescence to old age, and typical inpatients include …
Vitamin D receptor restricts T helper 2-biased inflammation in the heart
Authors: Jiangping Song, Xiao Chen, Liang Cheng, Man Rao, Kai Chen, Ningning Zhang, Jian Meng, Mengmeng Li, Zhi-Qiang Liu, Ping-Chang Yang
Journal: Cardiovascular Research (2018)

The aberrant immune responses play a critical role in the pathogenesis of myocarditis. Vitamin D receptor (VDR) has immune regulatory functions. This study aims to investigate the role of VDR in restricting the immune inflammation in the heart. The human heart samples were obtained from the heart transplantation. T helper (Th)2 and Th1 responses in the heart tissue were characterized by histology and immune assay. VDR−/− mice and recombination activating gene 2−/− mice were used in the experiments to test the role of VDR in maintaining the homeostasis in the heart. The results showed that, besides tissue damage, lower expression of VDR, high frequency of Th2 cells and increase in Th2 cytokines in the hearts of patients with myocarditis at the end stage of heart failure. The spontaneous Th2-biased inflammation was observed in the hearts of VDR−/− mice. CD4+ T cells from the VDR−/− mouse hearts were at highly activating status. The naïve VDR−/− CD4+ T cells and naïve CD4+ T cells from human hearts with myocarditis were prone to differentiate into Th2 cells. VDR formed complexes with GATA3, the interleukin (IL)-4 transcription factor, to prevent the Il4 gene transcription. Transplantation with VDR−/−CD4+ T cells induced the Th2-biased inflammation in the hearts of Rag2−/− mice. Reconstitution of VDR in CD4+ T cells inhibited the Th2-biased inflammation in the heart. VDR-deficiency contributes to the pathogenesis of myocarditis. To enhance the VDR expression in CD4+, T cells haves the therapeutic potential for the treatment of myocarditis.
Optimizing Hybrid Closed-Loop Therapy in Adolescents and Emerging Adults Using the MiniMed 670G System
Authors: Laurel H. Messer, Gregory P. Forlenza, Jennifer L. Sherr, R. Paul Wadwa, Bruce A. Buckingham, Stuart A. Weinzimer, David M. Maahs, Robert H. Slover
Journal: Diabetes Care (2018)

OBJECTIVE The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin delivery patterns and time-in-range metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system. RESEARCH DESIGN AND METHODS Data from 31 adolescent and young adult participants (14–26 years old) at three clinical sites in the 670G pivotal trial were analyzed. Participants had a 2-week run-in period in OL, followed by a 3-month in-home study phase with HCL functionality enabled. Data were compared between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months. RESULTS Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all meals with HCL compared with baseline OL. Total daily insulin dose and basal-to-bolus ratio did not change during the trial. Time in range increased 14% with use of Auto Mode after 3 months (P &amp;lt; 0.001), and HbA1c decreased 0.75%. Auto Mode exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The percentage of time in Auto Mode gradually declined from 87%, with a final use rate of 72% (−15%). CONCLUSIONS In transitioning young patients to the 670G system, providers should anticipate immediate C-to-I ratio adjustments while also assessing active insulin time. Users should anticipate occasional Auto Mode exits, which can be reduced by following system instructions and reliably bolusing for meals. Unique 670G system functionality requires ongoing clinical guidance and education from providers.
ATRIAL FIBRILLATION GUT SYNDROME: SEVERE GASTROPARESIS WITH PYLORIC SPASM FOLLOWING RADIOFREQUENCY CATHETER ABLATION OF DRUG RESISTANT SYMPTOMATIC ATRIAL FIBRILLATION TREATED WITH BOTULINUM TOXIN INJECTION
Authors: Nasreen Shaikh, Lakshmi Kannan, Laleh Merikhi, Kenneth Granet
Journal: Journal of the American College of Cardiology (2018)
EFFECT OF LIRAGLUTIDE ON CARDIOVASCULAR OUTCOMES IN ELDERLY PATIENTS IN THE LEADER TRIAL
Authors: Matthew Gilbert, Stephen Bain, Edward Franek, Esteban Jodar-Gimeno, Michael Nauck, Richard Pratley, Rosângela Réa, José Saraiva, Søren Rasmussen, Karen Tornøe, Bernt Johan von Scholten, John B. Buse
Journal: Journal of the American College of Cardiology (2018)
Abstract 20385: Cardiac Autonomic Dysfunction and Incidence of Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Sunil K Agarwal, Justin Echouffo-Tcheugui, Chiadi Ndumele, Wayne Rosamond, Gerardo Heiss, Josef Coresh
Journal: Circulation (2016)

Introduction: Interventions to modify autonomic tone have been sought as a way to improve outcomes in heart failure (HF) patients. Low heart rate variability (HRV) measures signify autonomic dysfun...
Twenty-Four–Hour Ambulatory Blood Pressure Reduction Patterns After Renal Denervation in the SPYRAL HTN-OFF MED Trial
Authors: Kazuomi Kario, Michael Böhm, Felix Mahfoud, Raymond R. Townsend, Michael A. Weber, Manesh Patel, Crystal C. Tyson, Joachim Weil, Tolga Agdirlioglu, Sidney A. Cohen, Martin Fahy, David E. Kandzari
Journal: Circulation (2018)
Abstract P3-08-11: The prognostic impact of retinoic acid-induced 2 (RAI2) expression in ERα-positive breast cancer patients
Authors: S Nishikawa, N Kondo, Y Endo, Y Hato, T Hisada, M Nishimoto, Y Dong, K Okuda, H Kato, S Takahashi, R Nakanishi, T Toyama
Journal: Cancer Research (2018)

Abstract Background: Breast cancer cells disseminate to the bone marrow and form bone metastases in a large majority of late-stage patients. Retinoic Acid-Induced 2 (RAI2) was reported as a putative suppressor of early hematogenous dissemination of tumor cells to the bone marrow in breast cancer, particularly in estrogen receptor α (ERα)-positive breast cancer. Here, we investigated mRNA expression of RAI-2 in breast cancer patients during long-term follow-up. Materials and methods: A total of 451 invasive breast cancer tissues was available for analysis of RAI2 mRNA using a TaqMan PCR system. We also sought correlations between clinicopathological factors and levels of RAI2 expression in these samples. The expression of markers associated with tumor-initiating capacity, such as SNAI1, SNAI2 and VIM was also analyzed. The median follow-up period was 9.0 years. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: We found positive correlations between low expression of RAI2 mRNA and shorter disease-free survival and overall survival in breast cancer patients (P=0.003, P&amp;lt;0.0001, respectively), which was limited to ERα-positive patients (P=0.04, P=0.0009, respectively), and not seen in ERα-negative patients (P=0.52, P=0.27, respectively). Low RAI2 mRNA levels were positively correlated with high grade, ERα-negativity and PgR negativity. Multivariate analysis indicated that low level RAI2 mRNA expression was an independent factor for survival both overall in breast cancer and in ERα-positive breast cancer patients Multivariate analysis (ERα-positive breast cancer patients) OS Multivariate patientsp valueHR(95%CI)Tumor size≤2cm1390.83691 (Reference) &amp;gt;2cm207 1.08(0.54-2.28)Node statusNegative176&amp;lt;0.00011 (Reference) Positive144 4.72(2.33-10.34)Grade11240.95921 (Reference) 2•3218 0.98(0.50-2.14)RAI2 mRNA expressionhigh140&amp;lt;0.00011 (Reference) middle•low206 4.79(2.14-12.78) . Conclusion:We show that low expression of RAI2 is an independent factor predictive of a poor prognosis in ERα-positive breast cancer patients. RAI2 could be a promising candidate biomarker and therapeutic target in ERα-positive breast cancer to prevent dissemination to the bone marrow. Citation Format: Nishikawa S, Kondo N, Endo Y, Hato Y, Hisada T, Nishimoto M, Dong Y, Okuda K, Kato H, Takahashi S, Nakanishi R, Toyama T. The prognostic impact of retinoic acid-induced 2 (RAI2) expression in ERα-positive breast cancer patients [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 P3-08-11.
Abstract 16090: Coronary Artery Calcium and Mortality From Coronary Heart Disease, Cardiovascular Disease, and All Causes in Women vs. Men With Diabetes: The Coronary Calcium Consortium
Authors: Nathan D Wong, Amber Cordola-Hsu, Wenjun Fan, Michael J Blaha, Matthew J Budoff, Khurram Nasir, Seamus Whelton, Michael D Miedema, John Rumberger, Daniel S Berman
Journal: Circulation (2017)

Background: Coronary artery calcium (CAC) predicts coronary heart disease (CHD) and cardiovascular disease (CVD) events in adults with diabetes (DM); however, its sex-specific impact on CHD, CVD, a...
Does working in unrecognised posts such as clinical fellow or trust grade have a negative impact on your career pathway, even if you have gained membership of the Royal College of Physicians and previously worked in recognised posts?
Authors: Sabina Dosani
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't 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.
Selective Activation of Tumor Necrosis Factor Receptor <scp>II</scp> Induces Antiinflammatory Responses and Alleviates Experimental Arthritis
Authors: Roman Fischer, Marcel Proske, Maëlle Duffey, Hubert Stangl, George F. Martinez, Nathalie Peters, Alexandra Kraske, Rainer H. Straub, John R. Bethea, Roland E. Kontermann, Klaus Pfizenmaier
Journal: Arthritis & Rheumatology (2018)

Treg cells modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor II (TNFRII) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Treg cells. The purpose of the present study was to investigate the therapeutic activity of a novel TNFRII agonist in experimental arthritis as well as the role of different Treg cell subsets.A novel mouse TNFRII-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic engineering. Mouse T cells were incubated together with interleukin-2 and/or EHD2-sc-mTNFR2 , and the effects on Treg cells were analyzed by flow cytometry. Mice with collagen-induced arthritis (CIA) were treated with EHD2-sc-mTNFR2 or saline, and the therapeutic effects were monitored and characterized.Selective activation of TNFRII was found to expand both CD4+ and CD8+ Treg cells. Moreover, TNFRII activation elevated the number of CD4+CD25+ and CD8+CD25+ Treg cells and increased the number of FoxP3-expressing cells in CD8+, but not CD4+, Treg cells, indicating different mechanisms of TNFRII-induced expansion of diverse T cell subsets with suppressive activity. In the CIA model, we demonstrated that administration of the TNFRII agonist EHD2-sc-mTNFR2 led to the expansion of both CD4+ and CD8+ Treg cells in vivo and induced antiinflammatory responses that alleviated arthritis.Our findings support the use of TNFRII-selective therapeutics as an effective approach to the treatment of arthritic disease and possibly other inflammatory and autoimmune diseases.
Efficacy Of Nasal Allergen Provocation Test In The Diagnosis Of Dermatophagoides Pteronyssinus Allergic Rhinitis
Authors: Jose S. Rodriguez Canosa, Sandy Stephanie Aguilar Gavilanes, Raúl Lázaro Castro Almarales, Mirta Álvarez Castelló, Belkis Lopez Gonzalez, Mercedes Ronquillo Diaz, Mayda González León, Wendy Ramirez Gonzalez, Bárbara Ivonne Navarro Viltre, Maivis Cabrera Quiala, Maytee Mateo Morejon, Mary Carmen Reyes Zamora, Alexis Labrada Rosado
Journal: Journal of Allergy and Clinical Immunology (2018)
Increased permeability of blood vessels after reversible electroporation is facilitated by alterations in endothelial cell-to-cell junctions
Authors: Bostjan Markelc, Elisabeth Bellard, Gregor Sersa, Tanja Jesenko, Sandrine Pelofy, Justin Teissié, Robert Frangez, Marie-Pierre Rols, Maja Cemazar, Muriel Golzio
Journal: Journal of Controlled Release (2018)