tbuckley/cabot-search huggingface dataset:
Academic requirements for Certificate of Completion of Training in surgical training: Consensus recommendations from the Association of Surgeons in Training/National Research Collaborative Consensus Group
Authors: Mathew J. Lee, A. Bhangu, Natalie S. Blencowe, D. Nepogodiev, Vimal J. Gokani, Rhiannon L. Harries, M. Akinfala, O. Ali, W. Allum, D.C. Bosanquet, K. Boyce, M. Bradburn, S.J. Chapman, E. Christopher, I. Coulter, B.J.F. Dean, M. Dickfos, M. El Boghdady, M. Elmasry, S. Fleming, J. Glasbey, C. Healy, V. Kasivisvanathan, K.S. Khan, A.G. Kolias, S.M. Lee, D. Morton, J. O'Beirne, P. Sinclair, P.A. Sutton
Journal: International Journal of Surgery (2016)

Surgical trainees are expected to demonstrate academic achievement in order to obtain their certificate of completion of training (CCT). These standards are set by the Joint Committee on Surgical Training (JCST) and specialty advisory committees (SAC). The standards are not equivalent across all surgical specialties and recognise different achievements as evidence. They do not recognise changes in models of research and focus on outcomes rather than process. The Association of Surgeons in Training (ASiT) and National Research Collaborative (NRC) set out to develop progressive, consistent and flexible evidence set for academic requirements at CCT.A modified-Delphi approach was used. An expert group consisting of representatives from the ASiT and the NRC undertook iterative review of a document proposing changes to requirements. This was circulated amongst wider stakeholders. After ten iterations, an open meeting was held to discuss these proposals. Voting on statements was performed using a 5-point Likert Scale. Each statement was voted on twice, with ≥80% of votes in agreement meaning the statement was approved. The results of this vote were used to propose core and optional academic requirements for CCT.Online discussion concluded after ten rounds. At the consensus meeting, statements were voted on by 25 delegates from across surgical specialties and training-grades. The group strongly favoured acquisition of 'Good Clinical Practice' training and research methodology training as CCT requirements. The group agreed that higher degrees, publications in any author position (including collaborative authorship), recruiting patients to a study or multicentre audit and presentation at a national or international meeting could be used as evidence for the purpose of CCT. The group agreed on two essential 'core' requirements (GCP and methodology training) and two of a menu of four 'additional' requirements (publication with any authorship position, presentation, recruitment of patients to a multicentre study and completion of a higher degree), which should be completed in order to attain CCT.This approach has engaged stakeholders to produce a progressive set of academic requirements for CCT, which are applicable across surgical specialties. Flexibility in requirements whilst retaining a high standard of evidence is desirable.
Evaluation of a light-activated drug in a canine prostate model for focal therapy.
Authors: E. Bromley, J. C. Chen, F. Zheng, S. Wang, L. Keltner
Journal: Journal of Clinical Oncology (2010)

e15062 Background: Treatment of localized prostate cancer is undergoing an evolution from potentially morbid prostatectomy or whole gland radiotherapy to confined therapy aimed at known, identifiable tumor deposits. Talaporfin sodium is a light-activated drug in two phase III trials for liver cancer and in early development for prostate cancer and BPH. Three preclinical studies using a canine prostate model evaluated the treatment effect zone and damage to surrounding tissues induced by local activation of talaporfin sodium by a trans-urethrally placed LED array. Methods: A total of 17 dogs were evaluated. Thin LED arrays (1.2mm in diameter) were inserted into the prostatic urethra and dogs were given 25 mg/kg talaporfin sodium. A total light dose of 100J/cm or 200J/cm was delivered. Control animals received light but no drug. Prostate, bladder and urethral tissue were removed for microscopic analysis at sacrifice 48 hours after treatment. Results: All active-treated animals showed significant cell death in the prostate as confirmed by visual examination of dissected tissue and by microscopic analysis. The diameter of the treatment effect zone was consistent and well demarcated at 21.1 mm + 3.95 for all dogs given the 100J/cm light dose. Effect zone diameter was similar for the 200J/cm dose. Length of the treatment zone was proportional to the effective length of the LED array. Bladder was undamaged by treatment, while the highest light dose caused damage to the urethra. Illumination of the LED array in absence of drug had no discernable effect on tissues. Conclusions: Talaporfin sodium, when activated by transurethral placement of a thin LED array, caused consistent, thorough and effective destruction of prostate tissue in a canine model. Diameter of the treatment zone was predictable and contained within the prostate and the length of the zone could be manipulated by altering the length of the LED array. These results suggest that this method of treatment holds promise as an adaptable, controlled and effective means of destroying neoplastic tissue in the prostate. It is currently being evaluated in two human prostate trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Light Sciences Oncology Light Sciences Oncology Light Sciences Oncology
Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells
Authors: Saulius Žuklys, Adam Handel, Saule Zhanybekova, Fatima Govani, Marcel Keller, Stefano Maio, Carlos E Mayer, Hong Ying Teh, Katrin Hafen, Giuseppe Gallone, Thomas Barthlott, Chris P Ponting, Georg A Holländer
Journal: Nature Immunology (2016)
Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease
Authors: Patricia K. Nguyen, Evgenios Neofytou, June-Wha Rhee, Joseph C. Wu
Journal: JAMA Cardiology (2016)

Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist.To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them.Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included.One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity.Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.
Asymptomatic Clostridium difficile colonization in two Australian tertiary hospitals, 2012–2014: prospective, repeated cross-sectional study
Authors: L. Furuya-Kanamori, A.C.A. Clements, N.F. Foster, C.A. Huber, S. Hong, T. Harris-Brown, L. Yakob, D.L. Paterson, T.V. Riley
Journal: Clinical Microbiology and Infection (2016)
Oxaliplatin, 5-fluorouracil, and folinic acid as first-line treatment in metastatic or recurrent gastric cancer.
Authors: H. Kim, J. Yun, K. Kim, S. Kim, S. Lee, S. Bae, K. Lee, D. Hong, H. Park
Journal: Journal of Clinical Oncology (2010)

e14646 Background: Oxaliplatin has shown considerable activity and synergism with 5-fluorouracil (5-FU) in several phase II studies for treating advanced gastric cancer. We retrospectively determined the efficacy and safety of a combination of oxaliplatin, 5-FU, and folinic acid (FA) as first-line chemotherapy for patients with metastatic or recurrent gastric cancer. Methods: The records of 39 advanced gastric cancer patients who were treated with first-line combination chemotherapy at Soonchunhyang University Hospital between 2006 and 2009 were retrieved from a cancer chemotherapy database. The chemotherapy regimen consisted of oxaliplatin (100 mg/m2) and FA (200 mg/m2 in a 2-hour infusion), followed by 5-FU (2,400 mg/m2 in a 46-hour continuous infusion) every 2 weeks. Results: Thirty-nine patients were studied between January 2006 and August 2009. The median age of the patients was 63 years (range, 38-77 years); 95% of the patients (37/39) were Eastern Cooperative Oncology Group performance status was 0 or 1. Overall, 79% of the patients (31/39) were newly diagnosed, and 21% (8/39) had recurrent disease. The 39 patients received a total of 210 treatment cycles. The median number of cycles was 6 (range, 1∼16 cycles). None of the patients achieved a complete response (CR) and 11 patients achieved a partial response (PR), resulting in an overall response rate of 28.2%. Stable disease (SD) was observed in 14 (35.9%) patients. The median time-to-progression (TTP) was 4.3 months (95% CI, 2.0-6.5 months) and the median overall survival (OS) was 9.8 months (95% CI, 3.5-16.0 months). The main hematologic toxicities were anemia and neutropenia, which were observed in 119 (56.7%) and 100 (47.6%) cycles, respectively. Grade 3/4 neutropenia was observed in 32 cycles (15.2%). Two patients had febrile neutropenia. The main non- hematologic toxicity was constipation, which was observed in 91 cycles (46.2%). Peripheral neuropathy occurred in 71 cycles (33.8%); all cases were grade 1 or 2. Conclusions: This study showed that combination chemotherapy with oxaliplatin, 5-FU, and FA is well tolerated and active as first-line treatment in patients with metastatic or recurrent gastric cancer. No significant financial relationships to disclose.
Clinical course of patients (pts) with acquired resistance (AR) to EGFR tyrosine kinase inhibitors (TKI).
Authors: G. R. Oxnard, G. J. Riely, M. H. Arcila, M. G. Kris, W. Pao, M. Ladanyi, V. A. Miller
Journal: Journal of Clinical Oncology (2010)

7520 Background: Pts with EGFR mutant lung cancer develop AR (i.e., progressive disease (PD) after initial sensitivity) on erlotinib or gefitinib after a median of 12 months. An acquired EGFR mutation (T790M) has been found in approximately half of tumors with AR, suggesting a change in tumor biology. EGFR mutant cell lines that acquire the T790M mutation have been found to demonstrate a more indolent growth pattern (Chmielecki and Pao, AACR, 2009). The clinical course of pts with AR has not been described. Methods: Pts fitting the consensus definition of AR (Jackman, et al., JCO, 2009) were enrolled in a rebiopsy/tissue analysis protocol. Medical records were reviewed. The first biopsy obtained after AR was tested for EGFR T790M mutation, using detection of EGFR sensitizing mutation as a control for specimen quality and clonal relatedness. Factors associated with survival after AR were explored using univariate logrank testing and Cox models. Results: 106 pts with AR and a documented EGFR sensitizing mutation were analyzed. Median time to PD on erlotinib (n = 76), gefitinib (n = 24), XL647 (n = 6) was 13 months. 100 pts had rebiopsy tissue available, which was adequate for analysis in 90%. T790M was detected in 59%. With 26 month median follow-up after AR, median survival from time of AR was 16 months and median survival from start of TKI was 38 months. EGFR TKI was maintained in 95% of pts in addition to subsequent therapies; 31% of pts received single-agent TKI for ≥ 6 months after PD. Factors associated with survival after AR were PD in an existing vs. new site of disease (HR 0.43, p < 0.01) and the presence vs. absence of T790M mutation (HR 0.55, p = 0.046). Factors not significantly associated with survival after AR included exon 19 vs. exon 21 EGFR mutation, female vs. male gender, and Asian vs. non-Asian race. Conclusions: (1) The median survival of lung cancer pts with sensitizing EGFR mutations who develop AR on EGFR TKI is 16 months following PD. (2) Detection of T790M in rebiopsy tissue is associated with better survival after AR. (3) A proportion of pts can continue on EGFR TKI alone for months after PD. Supported by R21 CA115051-01. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Boehringer Ingelheim, Genentech, MolecularMD, Pfizer, Roche
“Teaching is so WEIRD”
Authors: David F. Lancy
Journal: Behavioral and Brain Sciences (2015)

Abstract Direct active teaching by parents is largely absent in children's lives until the rise of WEIRD (Western, educated, industrialized rich, democratic) society. However, as mothers become schooled and missionized – like Kline's Fijian subjects – they adopt “modern” parenting practices, including teaching. There is great variability, even within WEIRD society, of parental teaching, suggesting that teaching itself must be culturally transmitted.
Health department’s NHS accounts are “rotten,” say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2016)

The government has produced a “rotten” set of accounts for the NHS in England over the most recent financial year, MPs on the influential parliamentary Public Accounts Committee have said.

The Department of Health accounts1 for 2015-16 were repeatedly attacked and criticised by MPs during an angry session of the committee on 7 September when it questioned department officials about the figures and the concerns raised about them recently by the National Audit Office.2

The committee’s chair, Meg Hillier, Labour MP for Hackney South and Shoreditch, said that the committee had been concerned and disappointed that the department’s accounts …
Phase II study of 5-FU dose-adjusted mFOLFOX7 plus bevacizumab in patients with metastatic colorectal cancer (AJUST study).
Authors: Tomomi Yakabe, Tadamichi Denda, Yoshitaka Morita, Chu Matsuda, Ho Min Kim, Shinji Fujieda, Mutsumi Fukunaga, Koji Oba, Junichi Sakamoto, Hideyuki Mishima
Journal: Journal of Clinical Oncology (2014)

592 Background: Individual fluorouracil dose adjustment improved efficacy and toxicity in patients with colorectal cancer receiving FOLFOX. But the usefulness has not been studied in Japan. Methods: To evaluate the efficacy and toxicity of 5-FU dose-adjusted mFOLFOX7 plus bevecizumab, we conducted a multi-center phase II study of 5-FU dose-adjusted mFOLFOX7 plus bevacizumab as first line treatment in patients with metastatic colorectal cancer (AJUST study UMIN000007194). Blood samples were collected from patients receiving 46 hours continuous infusion of 5-FU therapy ( 2400mg/m 2 ). 5-FU measurement were performed using my 5FU R assay. 5FU dose were adjusted according to the AUC. The results were compared with previously reported data. Results: A total of 48 patients were registered between April 2012 to June 2013 from 11 institutions in Japan. They had a wide range of AUC from 14 to 37 mg.h/L . The AUC of 5FU were 22.58 ± 5.33 mg.h/L. 29 patients (60.4%) receiving mFOLFOX7 were in the AUC target range of 20-24 mg/h/L. 16 patients (33.3%) were below the target range, and only 3 patients (6.2%) were above the target range. Past reports showed the AUC of 5FU 20.35 ± 9.87 mg.h/L. Our results of AUC, patients below the target range, and within the target range did not show significant difference from previously reported data (p= 0.12, 0.76, 0.82 respectively), except patients above the target range (p=0.047). Conclusions: This is the first report of individual fluorouracil dose adjustment of mFOLFOX7 plus bevacizumab in Japan. The mean AUC and the percentage of patients below the target range were comparable with previously reported data. These results suggested that 5FU dose monitoring is also useful for Japanese patients. The efficacy and toxicity will be presented in the meeting. Clinical trial information: 000007194.
Bortezomib Plus Dexamethasone As Induction Treatment Followed by Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma: A Study From India
Authors: Shyam Aggarwal, Anshul Bhalla, S.L Khatri, Anand Simar S, Manorama Bhargava, R. Saran
Journal: Blood (2011)
Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Kevin N Sheth, Jordan J Elm, Bradley J Molyneaux, Holly Hinson, Lauren A Beslow, Gordon K Sze, Ann-Christin Ostwaldt, Gregory J del Zoppo, J Marc Simard, Sven Jacobson, W Taylor Kimberly
Journal: The Lancet Neurology (2016)
Eular evidence based recommendations for the diagnosis of hand osteoarthritis - Report of a task force of the EULAR standing committe for International Clinical Studies Including Therapeutics (ESCISIT)
Authors: W Zhang, M Doherty, B Leeb, L Alekseeva, N Arden, J Bijisma, F Dincer, K Dziedzic, H Hauselmann, P Kaklamanis, M Kloppenburg, S Lohmander, E Maheu, E Martin-Mola, K Pavelka, L Punzi, S Reiter, J Smolen, G Verbruggen, I Watt, I Zimmermann-Gorska
Journal: Annals of the Rheumatic Diseases (2007)
Phenome‐Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia
Authors: Jayanth Doss, Huan Mo, Robert J. Carroll, Leslie J. Crofford, Joshua C. Denny
Journal: Arthritis & Rheumatology (2016)

The differences between seronegative and seropositive rheumatoid arthritis (RA) have not been widely reported. We performed electronic health record (EHR)-based phenome-wide association studies (PheWAS) to identify disease associations in seropositive and seronegative RA.A validated algorithm identified RA subjects from the de-identified version of the Vanderbilt University Medical Center EHR. Serotypes were determined by rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) values. We tested EHR-derived phenotypes using PheWAS comparing seropositive RA and seronegative RA, yielding disease associations. PheWAS was also performed in RF-positive versus RF-negative subjects and ACPA-positive versus ACPA-negative subjects. Following PheWAS, select phenotypes were then manually reviewed, and fibromyalgia was specifically evaluated using a validated algorithm.A total of 2,199 RA individuals with either RF or ACPA testing were identified. Of these, 1,382 patients (63%) were classified as seropositive. Seronegative RA was associated with myalgia and myositis (odds ratio [OR] 2.1, P = 3.7 × 10-10 ) and back pain. A manual review of the health record showed that among subjects coded for Myalgia and Myositis, ∼80% had fibromyalgia. Follow-up with a specific EHR algorithm for fibromyalgia confirmed that seronegative RA was associated with fibromyalgia (OR 1.8, P = 4.0 × 10-6 ). Seropositive RA was associated with chronic airway obstruction (OR 2.2, P = 1.4 × 10-4 ) and tobacco use (OR 2.2, P = 7.0 × 10-4 ).This PheWAS of RA patients identifies a strong association between seronegativity and fibromyalgia. It also affirms relationships between seropositivity and chronic airway obstruction and between seropositivity and tobacco use. These findings demonstrate the utility of the PheWAS approach to discover novel phenotype associations within different subgroups of a disease.
Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters
Authors: Daniel P. Bermingham, Randy D. Blakely
Journal: Pharmacological Reviews (2016)

Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively). These transporters act to recapture their respective neurotransmitters after release, and disruption of clearance and reuptake has significant effects on physiology and behavior and has been linked to a number of neuropsychiatric disorders. To ensure adequate and dynamic control of these transporters, multiple modes of control have evolved to regulate their activity and trafficking. Central to many of these modes of control are the actions of protein kinases, whose actions can be direct or indirectly mediated by kinase-modulated protein interactions. Here, we summarize the current state of our understanding of how protein kinases regulate monoamine transporters through changes in activity, trafficking, phosphorylation state, and interacting partners. We highlight genetic, biochemical, and pharmacological evidence for kinase-linked control of DAT, NET, and SERT and, where applicable, provide evidence for endogenous activators of these pathways. We hope our discussion can lead to a more nuanced and integrated understanding of how neurotransmitter transporters are controlled and may contribute to disorders that feature perturbed monoamine signaling, with an ultimate goal of developing better therapeutic strategies.