tbuckley/cabot-search huggingface dataset:
What goes around comes around: modeling malaria transmission from humans back to mosquitos
Authors: Kazutoyo Miura, Peter D. Crompton
Journal: Journal of Clinical Investigation (2018)

Malaria, caused by mosquito-transmitted Plasmodium parasites, continues to take a major toll on global health. The development of drugs and vaccines that reduce malaria transmission from humans back to mosquitos could contribute to the control and eventual eradication of malaria, but research models for the early clinical evaluation of candidate interventions are lacking. In this issue of the JCI, Collins and colleagues report the successful transmission of Plasmodium falciparum parasites from humans to mosquitoes during controlled human malaria infection, thus providing a potential tool to accelerate the development of much needed transmission-blocking drugs and vaccines.
The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome
Authors: Carmela Ricciardelli, Tina Bianco-Miotto, Shalini Jindal, Lisa M. Butler, Samuel Leung, Catriona M. McNeil, Sandra A. O'Toole, Esmaeil Ebrahimie, Ewan K.A. Millar, Andrew J. Sakko, Alexandra I. Ruiz, Sarah L. Vowler, David G. Huntsman, Stephen N. Birrell, Robert L. Sutherland, Carlo Palmieri, Theresa E. Hickey, Wayne D. Tilley
Journal: Clinical Cancer Research (2018)

Purpose: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer. The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival.Experimental Design: AR positivity was assessed by immunostaining in two clinically validated primary breast cancer cohorts [training cohort, n = 219; validation cohort, n = 418; 77% and 79% estrogen receptor alpha (ERα) positive, respectively]. The optimal AR cut-point was determined by ROC analysis in the training cohort and applied to both cohorts.Results: AR was an independent prognostic marker of breast cancer outcome in 22 of 46 (48%) previous studies that performed multivariate analyses. Most studies used cut-points of 1% or 10% nuclear positivity. Herein, neither 1% nor 10% cut-points were robustly prognostic. ROC analysis revealed that a higher AR cut-point (78% positivity) provided optimal sensitivity and specificity to predict breast cancer survival in the training (HR, 0.41; P = 0.015) and validation (HR, 0.50; P = 0.014) cohorts. Tenfold cross-validation confirmed the robustness of this AR cut-point. Patients with ERα-positive tumors and AR positivity ≥78% had the best survival in both cohorts (P < 0.0001). Among the combined ERα-positive cases, those with comparable or higher levels of AR (AR:ERα-positivity ratio >0.87) had the best outcomes (P < 0.0001).Conclusions: This study defines an optimal AR cut-point to reliably predict breast cancer survival. Testing this cut-point in prospective cohorts is warranted for implementation of AR as a prognostic factor in the clinical management of breast cancer. Clin Cancer Res; 24(10); 2328-41. ©2018 AACR.
NHS considers locum fee cap to stop trusts being “ripped off”
Authors: Matthew Limb
Journal: BMJ (2015)

The NHS is considering a cap on agency staffing costs to prevent hospitals being “ripped off,” NHS England’s chief executive has said.

Simon Stevens said that introducing a cap could mean hospitals “acting collectively to set limits on what will be paid.” He said that this was one example of how the NHS would now take a more “coordinated” approach in tackling workforce issues and other key areas such as care system redesign.

Speaking at the King’s Fund’s fifth annual NHS leadership and management summit in London on 20 May, he acknowledged that current pressures were partly caused by the “atomisation” of the healthcare system. These pressures were also partly …
USE OF SERIAL NT-PRO BNP TESTING TO ESTIMATE RISK IN PATIENTS WITH ASYMPTOMATIC AORTIC VALVE STENOSIS: THE SEAS STUDY
Authors: Olav Wendelboe Nielsen, Ahmad Sajadieh, Michael Olsen, Ronnie Willenheimer, Anders Greve, Simon Ray, Christoph Nienaber, Kristian Wachtell
Journal: Journal of the American College of Cardiology (2018)
International medical students being used as “cash cows,” say doctors
Authors: Helen Jaques
Journal: BMJ (2012)

Universities are deliberately breaching the cap on the number of international medical students they can admit in order to raise money from the “extortionate” fees paid by foreign students, representatives at the BMA’s annual representative meeting have heard.

The maximum proportion of international students permitted at UK medical schools is 7.5%, but multiple medical schools are currently exceeding this cap to earn fees of up to £39 000 a …
Insulin Detemir Use Is Associated With Higher Occurrence of Hypoglycemia in Hospitalized Patients With Hypoalbuminemia
Authors: Irit Hochberg
Journal: Diabetes Care (2018)

The insulin analogs detemir and glargine are the two basal insulins commonly used in hospitalized patients (1). Their slow-release reservoir is different—serum albumin for detemir and subcutaneous microcrystals for glargine (2,3).

There is a common belief that detemir should be avoided in hypoalbuminemic patients because they have less predictable levels of free insulin, raising a concern for higher risk of hypoglycemia (4,5). Nevertheless, the guidelines recommend using either insulin with impartiality to hypoalbuminemia (1). There are no human studies on pharmacokinetics or outcomes of using detemir in hypoalbuminemic patients. Randomized controlled studies of detemir versus glargine have not found a difference in hypoglycemia (6–9), but these trials included only a few hundred patients who probably were not hypoalbuminemic. A recent retrospective study found a higher rate of hypoglycemia (<70 mg/dL) in determir-treated compared with glargine-treated inpatients (10).

We took advantage of the large Rambam Health Care Campus inpatient database to retrospectively compare hypoglycemia in inpatients with low albumin treated with detemir or glargine. Data were retrieved using MDClone (mdclone.com), a query tool that provides comprehensive patient-level data of wide-ranging variables in a defined time frame around an index event. The study was approved by the Rambam Institutional Review Board.

Data were collected for all patients over 18 years old hospitalized between 1 February 2012 and 31 December 2016, treated with detemir or glargine, and with at least one hospitalization albumin blood test. The date of lowest albumin level was set as the index event. Exclusion criteria were “obstetric ward” (where glargine is not used) and glucose <15 …
Medical managers give up licences to avoid investigation, says GMC
Authors: Abi Rimmer
Journal: BMJ (2016)

Medical managers are giving up their licences to practise with the General Medical Council (GMC) to avoid potential investigations, the GMC has said.

In October a former medical director at Royal Cornwall Hospitals NHS Trust became the first doctor to be erased from the UK register for misconduct in a managerial, rather than clinical, capacity. …
Lanthanide-doped nanoparticles conjugated with an anti-CD33 antibody and a p53-activating peptide for acute myeloid leukemia therapy
Authors: Fan Niu, Jin Yan, Bohan Ma, Shichao Li, Yongping Shao, Pengcheng He, Wanggang Zhang, Wangxiao He, Peter X. Ma, Wuyuan Lu
Journal: Biomaterials (2018)
Letter by Taegtmeyer and Karlstaedt Regarding Article, “Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)”
Authors: Heinrich Taegtmeyer, Anja Karlstaedt
Journal: Circulation (2018)
Abstract P4-06-06: Frequency of mutations in multi-gene panel testing of 3,011 breast cancer patients
Authors: AY Zhou, J van den Akker, A Zimmer, W McFadden
Journal: Cancer Research (2018)

Abstract Objectives: Here, we describe the characteristics of 3,011 individuals with a self-reported diagnosis of breast cancer who received a multi-gene panel genetic test for hereditary cancer risk. Methods: These 3,011 patients were referred physician order for a multi-gene, next generation sequencing panel for hereditary cancer risk. Analysis was limited to 19 genes associated with hereditary breast and ovarian cancer (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, TP53). All patient demographic information was collected via a self-reported online health history questionnaire. Results: In this cohort, the median reported age at breast cancer diagnosis was 49.3. Overall, 360 pathogenic or likely pathogenic variants were identified and reported. A total of 344 individuals were found to carry a single pathogenic mutation in one of the 19 genes analyzed, and 8 individuals were found to carry two concurrent pathogenic mutations in different genes. Notably, 173 of the 360 mutations identified were reported in the BRCA1 and BRCA2 genes (48.1%), yielding an overall BRCA1 and BRCA2 mutation carrier rate of 5.7%. Additionally, 12.2% of the cohort reported having bilateral breast cancer. The mutation carrier rate amongst these individuals was 15.0% (50/334), 60.8% of the mutations found in these individuals were in BRCA1 or BRCA2, and the average age at breast cancer diagnosis was 49.4 (43.3 amongst mutation carriers). In the entire cohort, a pathogenic mutation was identified in 15 of the 19 genes analyzed. Conclusion: In summary, the overall mutation carrier rate in this cohort for breast and ovarian cancer risk genes was 11.7% (352/3,011). Taken together, these data support the recommendation that all patients with breast cancer should undergo germline testing for hereditary cancer risk. Citation Format: Zhou AY, van den Akker J, Zimmer A, McFadden W. Frequency of mutations in multi-gene panel testing of 3,011 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 P4-06-06.
Questioning the Benefits of Private Vehicle Transportation vs Emergency Medical Services Transportation
Authors: Robert F. Smith
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 12822: Continuous Smoking Promotes Neoatherosclerosis Formation in Stent Restenotic Neointimal Tissue After Drug-Eluting Stent Implantation
Authors: Yasuhiro Uchida, Satoshi Ichimiya, Hideki Ishii, Koji Mizutani, Ryo Yamaguchi, Hideo Oishi, Yusuke Miki, Masanobu Fujimoto, Toshiki Kawamiya, Hirotsugu Mihara, Hitoshi Ichimiya, Shinji Hayano, Susumu Suzuki, Junji Watanabe, Masaaki Kanashiro, Tetsuya Amano, Tatsuaki Matsubara, Toyoaki Murohara
Journal: Circulation (2015)

Introduction: Despite the advance of drug-eluting stents (DES), late adverse events such as very late stent thrombosis (VLST) and late target lesion revascularization are of concern. Although continuous smoking is an independent risk factor of VLST, the pathogenic impact on in-stent restenotic neointimal tissue components after DES implantation remains unclear. Hypothesis: We assessed the hypothesis that continuous smoking after DES implantation might promote neoatherosclerosis formation in restenosis lesions. Methods: We enrolled 47 consecutive patients with in-stent restenosis requiring revascularization after DES implantation between January 2008 and March 2015. In advance, we excluded the patients with recurrent restenosis, thrombotic lesions, and total occlusion. For evaluation of in-stent tissue components, integrated backscatter intravascular ultrasound (IB-IVUS) was performed. Patients were divided into current smokers and nonsmokers including both previous smokers and never-smokers. Results: Of these patients, 12 (25.5%) were current smokers. On volumetric IB-IVUS analyses, current smokers had a significantly higher percentage of lipid tissue volume within the neointima and a significantly lower percentage of fibrous tissue volume than nonsmokers (42.9 ± 19.4 vs. 26.3 ± 12.8%; p = 0.03, and 55.1 ± 19.2 vs. 70.9 ± 11.9%; p = 0.04, respectively). Moreover, continuous smoking was positively correlated with the percentage of lipid volume on multiple linear regression analysis after adjustment for confounding factors (β = 0.35, p = 0.03). Interval from stent implantation was similar between current smokers and nonsmokers (44.6 ± 38.2 vs. 37.5 ± 29.1 months; p = 0.58). Conclusions: Continuous smoking was associated with larger lipid tissue volume within the neointima after DES placement, suggesting the development of neoatherosclerosis and vulnerable neointima. Thus continuous smoking might lead to future adverse coronary events.
How do the earnings of doctors compare with those of other occupations?
Authors: Tom Moberly
Journal: BMJ (2017)

In 2017, the median income across all doctors working full time in the UK was £75 577.

This makes doctors the seventh highest earning group across the 493 occupations categorised by the Office for National Statistics (ONS). The highest earning group is chief executives and senior officials, whose median pay is £89 825, and the second highest earning is air traffic controllers, whose median …
The cell fate determinant Scribble is required for maintenance of hematopoietic stem cell function
Authors: Juliane Mohr, Banaja P. Dash, Tina M. Schnoeder, Denise Wolleschak, Carolin Herzog, Nuria Tubio Santamaria, Sönke Weinert, Sonika Godavarthy, Costanza Zanetti, Michael Naumann, Björn Hartleben, Tobias B. Huber, Daniela S. Krause, Thilo Kähne, Lars Bullinger, Florian H. Heidel
Journal: Leukemia (2018)
PREDICTORS AND OUTCOMES ASSOCIATED WITH POST-OPERATIVE PERICARDIAL TAMPONADE IN TYPE A ACUTE AORTIC DISSECTION PATIENTS
Authors: Swechya Banskota, Arturo Evangelista, Thomas Gleason, Davide Pacini, Truls Myrmel, G. Chad Hughes, Derek Brinster, Maral Ouzounian, Daniel Montgomery, Eric Isselbacher, Christoph Nienaber, Nilto De Oliveira, Marc Schermerhorn, Joseph Coselli, Stuart Hutchison, Kim Eagle
Journal: Journal of the American College of Cardiology (2018)
Activity and safety of Nab-FOLFIRI and Nab-FOLFOX as first-line treatment for metastatic pancreatic cancer (phase II NabucCO study).
Authors: Elisa Giommoni, Evaristo Maiello, Vanja Vaccaro, Ermanno Rondini, Caterina Vivaldi, Giampaolo Tortora, Laura Toppo, Guido Giordano, Tiziana Pia Latiano, Lorenzo Antonuzzo, Cinzia Lamperini, Luca Boni, Francesco Di Costanzo
Journal: Journal of Clinical Oncology (2018)

351 Background: FOLFIRINOX is an approved regimen for metastatic pancreatic cancer (mPC). We performed a modification in FOLFIRINOX schedule, using nab-paclitaxel (nab-p) to obtain two regimens that could be as effective and less toxic than the original triplet. NabucCO study was a randomized phase II trial to assess activity and toxicity of nab-p instead of either oxaliplatin (Nab-FOLFIRI) or irinotecan (Nab-FOLFOX) in first line setting. Previous dose–finding NabucCO study defined that maximum tolerated dose of nab-p with FOLFIRI is 120 mg/m 2 , and with FOLFOX is 160 mg/m 2 . Methods: The study was a 1:1 parallel arm, open label, not comparative one to assess overall response rate (ORR) of Nab-FOLFIRI and Nab-FOLFOX as primary end-point. Patients (pts) with PS 0-1, untreated for mPC were randomized to receive leucovorin 400 mg/m 2 , 5FU bolus 400 mg/m 2 , 5FU 48h ci 2400 mg/m 2 , irinotecan 180 mg/m 2 plus nab-p 120 mg/m 2 (arm A) or leucovorin 400 mg/m 2 , 5FU bolus 400 mg/m 2 , 5FU 48h ci 2400 mg/m 2 and oxaliplatin 85 mg/m 2 iv plus nab-p 160 mg/m 2 (arm B) every 2 weeks for up to 12 cycles. Secondary end points were clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS), and safety. Results: From November 2015 to January 2017, 84 pts were treated (42 for each arm). Median age was 60 years (29-65) in arm A and 64 years (47-64) in arm B. The ORR was 31 % for both schedules, with a CBR of 69% and 71%, respectively. At a median follow-up of 11.4 months for arm A and 14.5 months for arm B (censored on august, 31 th 2017), 1-year survival is 41% and 50%, respectively. For Nab-FOLFIRI PFS and mOS were 6 months (90% CI: 4.9-8.0) and 13.2 months (90% CI: 8.3-14.8), while in Nab-FOLFOX were 5.6 months (90% CI:4.9-7.2) and 10.8 months (90% CI: 8.4-12.8). Grade ≥3 toxicities in arm A were neutropenia (19%) and febrile neutropenia (12%). In arm B, main grade ≥3 toxicities were neutropenia (29%), fatigue (14%), peripheral neuropathy (7%). No toxic death were registered. Conclusions: Nab-FOLFIRI and Nab–FOLFOX demonstrated a similar activity to FOLFIRINOX, with better safety profile in terms of neutropenia, fatigue and neuropathy. These results could justify a future phase III evaluation. Clinical trial information: NCT02109341.
Erratum: Corrigendum: Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Authors: Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, LiPing Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
Journal: Nature Neuroscience (2014)
Budget cuts force local councils into “narrow” focus on social care, warns watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Local authorities in England are being forced to prioritise adult social care over other vital services such as housing because of swingeing central budget cuts, the public spending watchdog has warned.

In a report published on 8 March,1 the National Audit Office (NAO) said that the financial health of local authorities across England was worsening, with councils struggling with higher demand and cost pressures against central funding cuts of nearly 50% since 2010-11.

While local authorities have been granted more freedom to increase council tax bills and have received one-off short term funds from …
I want to specialise in ultrasound (general, vascular, and gynaecological). Do I have to do an MSc in ultrasound or is there any other way?
Authors: Alan Denison
Journal: BMJ (2004)

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.
Characteristics of circulating tumor cells in newly diagnosed metastatic pancreatic adenocarcinoma.
Authors: Jason Scott Starr, Hiral D. Parekh, Jose I. Varillas, Alison Marguerite Ivey, Isis Barnes, Margaret A. McEwan, Carmen Joseph Allegra, Jose Gilberto Trevino, Jessica Cioffi, Steven J. Hughes, Lazarus Mramba, Jinling Zhang, Z. Hugh Fan, Thomas J. George
Journal: Journal of Clinical Oncology (2018)

304 Background: Circulating tumor cells (CTCs) represent real time dissemination of solid tumors. Historically, CTC enumeration has been challenging to perform successfully in pancreatic cancer (PCa). Using a previously published microfluidic device designed to increase cell capture, we analyzed CTC characteristics in a cohort of newly diagnosed patients with metastatic PCa. Methods: After provision of informed consent, blood samples (7-10mL) were collected within 1 month of treatment initiation. Specimens were processed within 6 hours of collection. A UF developed microfluidic device was used to capture and identify EpCam+ CTCs. Isolated cells were verified as CTCs consistent with FDA-approved definitions (cytokeratin+, DAPI+, CD45-). Statistical analysis was performed using Scheffe’s method along with analysis of variance to test interactions between the clinical demographics and groups. The study was approved by the UF IRB. Results: A cohort of 27 patients had CTC determination at treatment onset with multi-agent chemotherapy for metastatic PCa. Cohort characteristics included: median age 65 (range 29-76), 63% male, 92% white, 85% with intact primary pancreatic tumor, pancreatic tumor location: head (n = 12), body (n = 5), tail (n = 6), number of sites of metastasis: 1 (n = 18), 2 (n = 7), 3 (n = 2), and median albumin 3.9 g/dl. Median CTC for the entire cohort was 7/mL of blood (range 2-12). CTCs were detected and quantified in all patients analyzed. In those with intact primary tumors, there were no significant differences in CTCs based on age (≥65), sex, albumin (≥3.5 g/dl), or number of metastatic organ sites (1, 2, or 3). However, primary tumor location in the head vs. tail was different (mean 7.7 vs. 4.3/mL; p = 0.02; CI -5.78 – [-] 0.41). Conclusions: This analysis demonstrates the feasibility of measuring CTCs in patients with metastatic PCa. CTC amount does not appear impacted by systemic tumor burden or demographic differences. However, anatomic differences in primary tumor location may be important in CTC studies. Further analysis of a larger and more diverse patient data set is planned.