tbuckley/cabot-search huggingface dataset:
Air Toxics in Relation to Autism Diagnosis, Phenotype, and Severity in a U.S. Family-Based Study
Authors: Amy E. Kalkbrenner, Gayle C. Windham, Cheng Zheng, Rob McConnell, Nora L. Lee, James J. Schauer, Brian Thayer, Juhi Pandey, Heather E. Volk
Journal: Environmental Health Perspectives (2018)

Background: Previous studies have reported associations of perinatal exposure to air toxics, including some metals and volatile organic compounds, with autism spectrum disorder (ASD). Objectives: Our goal was to further explore associations of perinatal air toxics with ASD and associated quantitative traits in high-risk multiplex families. Methods: We included participants of a U.S. family-based study [the Autism Genetic Resource Exchange (AGRE)] who were born between 1994 and 2007 and had address information. We assessed associations between average annual concentrations at birth for each of 155 air toxics from the U.S. EPA emissions-based National-scale Air Toxics Assessment and a) ASD diagnosis (1,540 cases and 477 controls); b) a continuous measure of autism-related traits, the Social Responsiveness Scale (SRS, among 1,272 cases and controls); and c) a measure of autism severity, the Calibrated Severity Score (among 1,380 cases). In addition to the individual's air toxic level, mixed models (clustering on family) included the family mean air toxic level, birth year, and census covariates, with consideration of the false discovery rate. Results: ASD diagnosis was positively associated with propionaldehyde, methyl tert-butyl ether (MTBE), bromoform, 1,4-dioxane, dibenzofurans, and glycol ethers and was inversely associated with 1,4-dichlorobenzene, 4,4′-methylene diphenyl diisocyanate (MDI), benzidine, and ethyl carbamate (urethane). These associations were robust to adjustment in two-pollutant models. Autism severity was associated positively with carbon disulfide and chlorobenzene, and negatively with 1,4-dichlorobenzene. There were no associations with the SRS. Conclusions: Some air toxics were associated with ASD risk and severity, including some traffic-related air pollutants and newly-reported associations, but other previously reported associations with metals and volatile organic compounds were not reproducible. https://doi.org/10.1289/EHP1867
Abstract 20297: Overloaded High Density Lipoprotein Particles & Incident Cardiovascular Events
Authors: Thomas Sperry, Anand Rohatgi, Amit Khera, Ian Neeland, Parag Joshi, Colby Ayers
Journal: Circulation (2016)

Background:  Increased high-density cholesterol content (HDL-C) indexed to HDL particle concentration (HDL-P), termed “cholesterol overloaded HDL,” has been associated with subclinical atherosclerosis in a low risk cohort. However, it remains unclear how indices of HDL composition associate with incident atherosclerotic cardiovascular disease (ASCVD) events and cholesterol efflux, a key anti-atherosclerotic pathway. HDL particle size is also considered an important parameter but has not been studied indexed to particle concentration.   Methods:  HDL-C, HDL-P, and HDL particle size by NMR, and cholesterol efflux capacity from macrophages to apolipoprotein B-depleted plasma at baseline were measured in 2417 participants, ages 30 to 65, enrolled in the Dallas Heart Study, a probability based population sample. The associations of two indexes of HDL composition, HDL-C/HDL-P and HDL size/HDL-P, were assessed using multivariable Cox proportional hazards models. The primary ASCVD endpoint included first myocardial infarction, nonfatal stroke, coronary revascularization, or cardiovascular death.   Results:  In a fully adjusted model that included traditional risk factors, the highest versus lowest quartiles of HDL-C/HDL-P and HDL-Size/HDL-P were both associated with a significant increase in incident ASCVD (HDL-C/HDL-P: HR 2.12, 95% CI 1.18 - 3.80; HDL-Size/HDL-P: HR 1.89, 95% CI 1.17 to 3.05). Cholesterol efflux capacity was inversely associated with HDL-Size/HDL-P (p=0.012) but not with HDL-C/HDL-P (p=0.517).   Conclusion:  Overloaded HDL, as measured by increased HDL-C/HDL-P or HDL size/HDL-P, associates with an increased risk of incident ASCVD and may partially reflect dysfunctional HDL as assessed by lower cholesterol efflux. These findings highlight the importance of comprehensive assessment of HDL composition markers for ASCVD risk.
Alpha‐fetoprotein in liver transplantation for hepatocellular carcinoma: The lower, the better
Authors: Vincenzo Mazzaferro, Michele Droz dit Busset, Sherrie Bhoori
Journal: Hepatology (2018)

Mazzaferro, Vincenzo M.D., Ph.D.; Droz dit Busset, Michele M.D.; Bhoori, Sherrie M.D. Author Information
Royal College of Obstetricians and Gynaecologists mentoring scheme
Authors: Charnjit Dhillon
Journal: BMJ (2004)

<i>The Royal College of Obstetricians and Gynaecologists recently set up a mentoring service for doctors in difficulty.</i> Peter Bowen-Simpkins, Heather Mellows<i>, and</i> Charnjit Dhillon <i>explain how they developed and are implementing this scheme. Other colleges take note</i>
I am a fourth year medical student and am interested in mountain medicine, medical rescue operations, and expedition medicine. What should I do and how should I train for this? Is it super-specialisation? Do I need to complete my postgraduation in general surgery or medicine or general practice before getting enrolled in this field?
Authors: Mark Wilson
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>
3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances
Authors: Soroosh Derakhshanfar, Rene Mbeleck, Kaige Xu, Xingying Zhang, Wen Zhong, Malcolm Xing
Journal: Bioactive Materials (2018)

3D printing, an additive manufacturing based technology for precise 3D construction, is currently widely employed to enhance applicability and function of cell laden scaffolds. Research on novel compatible biomaterials for bioprinting exhibiting fast crosslinking properties is an essential prerequisite toward advancing 3D printing applications in tissue engineering. Printability to improve fabrication process and cell encapsulation are two of the main factors to be considered in development of 3D bioprinting. Other important factors include but are not limited to printing fidelity, stability, crosslinking time, biocompatibility, cell encapsulation and proliferation, shear-thinning properties, and mechanical properties such as mechanical strength and elasticity. In this review, we recite recent promising advances in bioink development as well as bioprinting methods. Also, an effort has been made to include studies with diverse types of crosslinking methods such as photo, chemical and ultraviolet (UV). We also propose the challenges and future outlook of 3D bioprinting application in medical sciences and discuss the high performance bioinks.
Predicting the Effect of Fenofibrate on Cardiovascular Risk for Individual Patients With Type 2 Diabetes
Authors: Charlotte Koopal, Frank L.J. Visseren, Jan Westerink, Yolanda van der Graaf, Henry N. Ginsberg, Anthony C. Keech
Journal: Diabetes Care (2018)

In clinical trials, treatment with fenofibrate did not reduce the incidence of major cardiovascular events (MCVE) in patients with type 2 diabetes mellitus (T2DM). However, treatment effects reported by trials comprise patients who respond poorly and patients who respond well to fenofibrate. Our aim was to use statistical modeling to estimate the expected treatment effect of fenofibrate for individual patients with T2DM.To estimate individual risk, the FIELD risk model, with 5-year MCVE as primary outcome, was externally validated in T2DM patients from ACCORD and the SMART observational cohort. Fenofibrate treatment effect was estimated in 17,142 T2DM patients from FIELD, ACCORD, and SMART. Individual treatment effect, expressed as absolute risk reduction (ARR), is the difference between treated and untreated MCVE risk. Results were stratified for patients with and without dyslipidemia (i.e., high triglycerides and low LDL cholesterol).External validation of the FIELD risk model showed good calibration and moderate discrimination in ACCORD (C-statistic 0.67 [95% CI 0.65-0.69]) and SMART (C-statistic 0.66 [95% CI 0.63-0.69]). Median 5-year MCVE risk in all three studies combined was 6.7% (interquartile range [IQR] 4.0-11.7) in patients without (N = 13,224) and 9.4% (IQR 5.4-16.1%) in patients with (N = 3,918) dyslipidemia. The median ARR was 2.15% (IQR 1.23-3.68) in patients with dyslipidemia, corresponding with a number needed to treat (NNT) of 47, and 0.22% (IQR 0.13-0.38) in patients without dyslipidemia (NNT 455).In individual patients with T2DM, there is a wide range of absolute treatment effect of fenofibrate, and overall the fenofibrate treatment effect was larger in patients with dyslipidemia. The method of individualized treatment effect prediction of fenofibrate on MCVE risk reduction in T2DM can be used to guide clinical decision making.
ADENOSINE AFTER LEFT ATRIAL APPENDAGE ISOLATION: ACUTE RESULTS
Authors: Carola Gianni, Sanghamitra Mohanty, Chintan Trivedi, Domenico G. Della Rocca, Amin Al-Ahmad, John Burkhardt, G. Gallinghouse, Patrick Hranitzky, Rodney Horton, Javier Sanchez, Luigi Di Biase, Andrea Natale, Claude Elayi
Journal: Journal of the American College of Cardiology (2018)
THE SGLT2 INHIBITOR EMPAGLIFLOZIN DOES NOT EXHIBIT PRO THROMBOTIC EFFECTS
Authors: Carlos G. Santos-Gallego, Mohammad Zafar, Rodolfo San Antonio, Juan Antonio Requena Ibanez, Maria Belen Picatoste Botija, Kiyotake Ishikawa, Shin Watanabe, Roger Hajjar, Valentin Fuster, Juan Badimon
Journal: Journal of the American College of Cardiology (2018)
Reducing antibiotic overuse in rural China
Authors: Liming Lu, Menghan Gao
Journal: The Lancet Global Health (2018)

Xiaolin Wei and colleagues (October, 2017)1 report their findings on the effect of training and educational interventions for physicians and caregivers on antibiotic use within paediatric settings in rural China. The study is meaningful, not only for China, but also from a global health perspective given the serious consequences of antibiotic misuse and overuse.2 Although the study is commendable and the results seem positive, some issues and obstacles might undermine the feasibility, sustainability, and generalisability of the proposed intervention strategy.
Efficacy of checkpoint inhibitors, tumor vaccines, and cellular immunotherapies in patients with advanced non-small cell lung cancer.
Authors: Yunfang Yu, Qiyun Ou, Ying Wang, Zhifeng Liu, Tuping Fu, Quanlong Gao, Dagui Lin, Herui Yao
Journal: Journal of Clinical Oncology (2018)

165 Background: Checkpoint inhibitors, tumor vaccines or cellular immunotherapies demonstrated prolonged survival versus placebo or observation in several randomized clinical trials (RCTs) of patients with advanced non-small-cell lung cancer (NSCLC). We aimed to clarify the benefits of imunotherapy by a meta-analysis of RCTs data. Methods: We searched for RCTs investigating immunotherapy versus placebo or observation in patients with advanced NSCLC. Overall survival (OS) and progression-free survival (PFS) were calculated as combined hazard ratios (HRs). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 23 RCTs including a total of 8,956 patients were identified (5,142 patients in the immunotherapy group and 3,814 in the placebo or observation group). High- to moderate-quality evidence indicated that immunotherapy prolonged OS (HR = 0.79, 95% confidence interval (CI) 0.75 to 0.84, P &lt; 0.0001) and PFS (HR = 0.80, 95% CI 0.73 to 0.88, P &lt; 0.0001). In subgroup analysis, high- to moderate-quality evidence revealed immunotherapy extended NSCLC survival and PFS in tumor vaccines (HR, 0.84, 95% CI 0.76 to 0.92 and 0.86, 95% CI 0.78 to 0.94 for OS and PFS, respectively), checkpoint inhibitors (0.77, 95% CI 0.72 to 0.83 and 0.78, 95% CI 0.68 to 0.90, respectively), maintenance therapy (0.77, 95% CI 0.71 to 0.83 and 0.78, 95% CI 0.66 to 0.91, respectively), first-line therapy (0.89, 95% CI 0.80 to 0.98 and 0.76, 95% CI 0.64 to 0.91, respectively), previous definitive chemotherapy (0.72, 95% CI 0.67 to 0.78 and 0.87, 95% CI 0.79 to 0.95, respectively), and concurrent chemotherapy (0.87, 95% CI 0.80 to 0.95 and 0.84, 95% CI 0.77 to 0.91, respectively). There was a benefit of immunotherapy in previous definitive chemotherapy compared with chemoradiotherapy and with concurrent administration of chemotherapy (OS as HR: P = 0.002 and P = 0.006, respectively). Conclusions: This analysis provides strong evidence for OS and PFS benefit of immunotherapy in patients with advanced NSCLC, particularly in those receiving tumor vaccines, checkpoint inhibitors, maintenance and first-line therapy, previous definitive chemotherapy, and with concurrent chemotherapy.
Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment
Authors: Kyohei Nakamura, Sahar Kassem, Alice Cleynen, Marie-Lorraine Chrétien, Camille Guillerey, Eva Maria Putz, Tobias Bald, Irmgard Förster, Slavica Vuckovic, Geoffrey R. Hill, Seth L. Masters, Marta Chesi, P. Leif Bergsagel, Hervé Avet-Loiseau, Ludovic Martinet, Mark J. Smyth
Journal: Cancer Cell (2018)
OPTIMIZATION OF ACUTE RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY WITH A QUADRIPOLAR LV LEAD: SHOULD WE USE THE PRESSURE DERIVATE DP/DTMAX OR STROKE WORK DERIVED FROM PRESSURE-VOLUME LOOPS?
Authors: Alwin Zweerink, Wouter van Everdingen, Uyen C. Nguyên, Albert van Rossum, Pieter Doevendans, Kevin Vernooy, Mathias Meine, Cornelis Allaart
Journal: Journal of the American College of Cardiology (2018)
Effects of cabozantinib on bone turnover markers in patients with metastatic renal cell carcinoma.
Authors: Raffaele Ratta, Elena Verzoni, Francesco Pantano, Paolo Grassi, Antonia Martinetti, Daniele Morelli, Elisa Sottotetti, Roberta Mennitto, Giovanni Fucà, Michele Prisciandaro, Filippo G. De Braud, Daniele Santini, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2018)

638 Background: In-vitro studies have shown that cabozantinib has a strong inhibitory action on osteoclast differentiation and bone-resorption activity. The aim of this analysis was to investigate the effects of cabozantinib on bone turnover markers in patients (pts) with metastatic renal cell carcinoma (mRCC). Methods: We included mRCC pts treated with cabozantinib within the Italian Managed Access Program (MAP) at the Istituto Nazionale Tumori of Milan (Italy). Plasma samples from every patient were collected at baseline and after 3 and 6 months of treatment. The bone resorption markers C-terminal telopeptide of type I collagen (CTx) and tartrate-resistant acid phosphatase isoenzyme 5b (TRACP 5b), the osteoclastogenesis markers osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL), vitamin D and parathormone (PTH) were measured by immunometric assay techniques. Data were analyzed using the RM One-Way ANOVA test with Greenhouse-Geisser correction followed by uncorrected Fisher’s LSD multiple comparison tests with individual variances computed for each comparison. Statistical tests were performed using the program GraphPad Prism (San Diego, CA). Results: Twenty-two pts have been treated with cabozantinib. Mature data were available for 11 pts. Analysis of TRACP 5b, OPG, RANKL and vitamin D did not show any significant variations during treatment with cabozantinib. CTx showed a significant reduction after 6 months of treatment (MV 171.5 pg/mL, STD 208.4) from baseline (mean value [MV] 352.2 pg/mL, standard deviation [STD] 210.1) (p = 0.0439) in the whole study population. PTH levels significantly increased after 3 months of treatment (MV 86.79 pg/mL, STD 34.99) from baseline (MV 30.77 pg/mL, STD 12.64) (p = 0.0003), while significantly decreased after 6 months (MV 75.01 pg/mL, STD 53.1) (p = 0.0174). Conclusions: Our data suggested that cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx; it was also associated with an asymptomatic transient secondary increase of parathormone. This is the first clinical evidence on effects of cabozantinib on bone metabolism in a small population of mRCC pts.
Doctors must avoid jargon when talking to patients, royal college says
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors should speak slowly and avoid using jargon with their patients, the Royal College of General Practitioners (RCGP) has said.1

A report by the college said that doctors often used words that were unfamiliar to patients or that patients did not fully understand. “Doctors may use familiar words in unfamiliar ways,” it said. “For example, when health practitioners use the term ‘chronic’ they frequently mean ‘persistent,’ whereas a common alternative understanding of the word is to mean ‘severe.’”

The report said, “Doctors …
Plans to protect whistleblowers “a great leap forward”
Authors: Clare Dyer
Journal: BMJ (2018)

New draft regulations put before parliament on 19 March will protect whistleblowers who have raised concerns with one NHS employer from being refused another job elsewhere in the NHS as a consequence.

The regulations implement a recommendation by Robert Francis, who chaired the Freedom to Speak Up review in 2015. The review found that some health professionals struggled to find employment after speaking up about patient safety. Francis also chaired inquiries into failings at Mid Staffs NHS Foundation Trust, which revealed a culture that deterred staff from raising concerns.

Fears that doctors and nurses in the NHS, a monopoly employer, can damage their …
Electronic fetal heart rate monitoring: we need new research approaches
Authors: Susan Bewley, Alain Braillon
Journal: BMJ (2018)

We commend The BMJ for the timely head to head debate on electronic fetal heart monitoring,1 in which the doctors supporting monitoring seem to cherry pick evidence, and the principal investigator of many great obstetric trials (including INFANT, a randomised controlled trial of 47 062 women undergoing continuous electronic fetal heart rate monitoring) explains the uncertainties. 

Cochrane, the International Federation of Gynecology and Obstetrics, and the National Institute for Health and Care Excellence have all said that no evidence …
Proportion of biochemically-recurrent prostate cancer patients with durable undetectable PSA after short-course androgen deprivation therapy.
Authors: Daniel M. Lim, Roman Gulati, Serge Aleshin-Guendel, Heather H. Cheng, Agnes M. Gawne, Jonathan T. Wingate, Ruth Douglas Etzioni, Evan Y. Yu
Journal: Journal of Clinical Oncology (2018)

207 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate specific antigen (PSA) levels as a marker of efficacy. The proportion of patients and clinical relevance of those with a prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥ 0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death from any cause were evaluated by log-rank tests. Results: After ineligibility exclusions, data were abstracted from 93 patients. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were n=23/93 (24.7%; 95% CI 16.4–34.8%; P&lt;0.001) and n=14/93 (15.1%; 95% CI 8.5–24.0%; P&lt;0.001), respectively. Proportions of patients with undetectable PSA 12 and 24 months after testosterone recovery ≥ 50 ng/dL were n=16/65 (24.6%; 95% CI 14.8-36.9%) and n=10/65 (15.4%; 95% CI 7.6-26.5%), respectively. Being 1 year older at diagnosis was associated with an 11.5% (95% CI 3.1–21.9%; P=0.01) increase in the odds of having a detectable PSA after controlling for PSA at diagnosis, Gleason sum and time from initial therapy to BCR. Detectable PSA was associated with increased risk of metastasis (P=0.006) with marginal evidence of association with death from any cause (P=0.07). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. Additional analysis is needed to demonstrate the clinical value of this measure as a surrogate for prostate cancer outcomes and for consideration as a trial endpoint.
ELEVATED CRP LEVELS DO NOT ADVERSELY MODULATE THE ABILITY OF EVOLOCUMAB TO REGRESS CORONARY ATHEROSCLEROSIS: INSIGHTS FROM GLAGOV
Authors: Adam J. Nelson, Rishi Puri, Christie Ballantyne, Leslie Cho, Danielle Brennan, Helina Kassahun, Ransi Somaratne, Scott Wasserman, Steven Nissen, Stephen Nicholls
Journal: Journal of the American College of Cardiology (2018)
Anal Malignant Melanoma Manifesting Hepatic Metastases Shown on FDG PET/CT
Authors: Sijuan Zou, Zhaoting Cheng, Shuang Song, Dong Kuang, Xiaohua Zhu
Journal: Clinical Nuclear Medicine (2018)

Multiple hepatic metastases are uncommon as initial presentation of primary anal malignant melanoma. We report FDG PET/CT findings of pathology-proven hepatic metastases from anal malignant melanoma of unknown origin in a 43-year-old woman whose initial presentation was worsening abdominal pain.
BMA supports coupling undergraduate medicine with foundation year 1
Authors: Helen Jaques
Journal: BMJ (2012)

The BMA has agreed to look into coupling the first year of the foundation programme with the undergraduate medical course to ensure that UK medical graduates are able to secure a job and, subsequently, full registration with the General Medical Council on graduation.

On graduation from medical school, new doctors are granted provisional registration with the GMC and are able to obtain their full licence to …