bluuebunny/crossref_metadata_2025 huggingface dataset:
A Model Applied to a Real Life Situation: Self-Management with a Written Action Plan for Early Treatment of COPD Exacerbations
Authors: Nault Diane , Sedano Maria F. , Soto Lorena , Joubert Alexandre , Drouin Isabelle , Bourbeau Jean
Published: May 2017

Background: We hypothesized that self-management education with the use of a written action plan provided by a nurse case manager can help patients to gain the proper skills to start an early treatment for an acute exacerbation.

Methods: COPD patients from an outpatient clinic with access to a written action plan and self-administered prescription were instructed to initiate their antibiotics and/or prednisone in case of exacerbation, and call their nurse case manager for supervision. The following data was collected: symptoms change, patients delay in taking action to treat their exacerbations (starting antibiotics and prednisone, calling the case manager) and use of hospital services.

Results: We report on 187 exacerbations occurring in a cohort of 113 moderate / severe COPD patients with FEV1 of 37 ± 16% predicted (mean ± SD). 161 exacerbations were supervised by the case manager at the time of the event. The remaining 26 exacerbations were detected after the event. 87% of the supervised exacerbations presented with 2 major symptoms (increased dyspnea, increased sputum volume and/or purulent sputum). Patient’s delay to initiate treatment in supervised exacerbations was 2.04 ± 1.8 days; 85% took action to treat the exacerbation within 3 days. The treatment for supervised and unsupervised exacerbations was similar (slightly more antibiotics and prednisone were used for unsupervised ones) and they had similarly favourable outcomes in terms of health services use, with 68.5% of the exacerbations not requiring any hospital services.

Conclusions: Patients can take an active role, acquire the skills to recognize exacerbation symptoms and start an early treatment of antibiotics and prednisone according to the directives of their written action plan.
Attenuation of the Threshold for Myocardial Ischemia in Ramp vs Standard Bruce Protocol in Patients with Positive Exercise Stress Test and Angiographically Demonstrated Coronary Artery Narrowing?
Authors: Noel Martin , Jobin Jean , Marcoux Audrey , Boyer Luce , Dagenais Gilles R. , Bogaty Peter
Published: May 2017

Background: Gradual instead of abrupt increases in workload favour a more physiological response in terms of hemodynamic and gas exchange parameters. Therefore, we sought to determine whether myocardial ischemia is attenuated with a ramp compared to a standard Bruce exercise protocol in patients with coronary artery disease (CAD).

Methods: We compared ischemic parameters on the Bruce protocol with an individualized ergocycle ramp protocol in 18 men with documented CAD (≥ 70% stenosis) and a reproducible ischemic ECG exercise test. These 2 symptom-limited tests were performed in random order 2 weeks apart. Oxygen consumption (VO2), ischemic threshold [systolic blood pressure x heart rate (RPP) at 1 mm ST-segment depression], and maximum ST-segment depression corresponding to the highest RPP common to the 2 tests (AdjSTmax) were determined.

Results: While all subjects showed ischemia on the treadmill, 6/18 did not on the ergocycle. However, ischemic threshold was higher on the ramp than the Bruce protocol (23 420 ± 5 732 vs 20 018 ± 3 542 bpm•min-1•mmHg; P=0.007). Peak RPP was higher during the ramp than with the Bruce protocol (28 492 ± 6 450 vs 25 519 ± 6 067 bpm•min-1•mmHg, respectively; P=0.02), despite similar peak VO2 (25.59 ± 5.05 vs 26.39 ± 4.65 mlO2•kg-1•min-1, respectively; P=0.6). AdjSTmax was less on the ramp than the Bruce protocol (-1.2 ± 0.9 vs -1.9 ± 0.7 mm; P=0.003).

Conclusion: Exercise-induced myocardial ischemia is markedly attenuated on the more gradually increasing workload of the individualized ramp ergocycle compared with the standard Bruce treadmill protocol. This effect is unexplained by energy expenditure (VO2) or myocardial work (RPP) and is consistent with a “warm-up” ischemic mechanism. The more gradually increasing workload of the ramp ergocycle protocol may have favoured a “warm-up” ischemic effect despite achieving higher RPP than the Bruce protocol treadmill suggesting it may be physiologically preferable for exercise prescription in patients with CAD.
11. Who is in charge? Introducing criteria to evaluate health human resource (HHR) policy documents
Authors: Rosenfield D. , Abrahams C. , Verma S.
Published: May 2017

The maldistribution of and lack of access to health professionals continues to be a major issue for policymakers at all levels of government. Additionally, the basis by which Health Human Resource (HHR) policy is determined is unclear. Publications found in independent reports, peer-reviewed journals and most importantly, grey literature, can significantly influence or inform major policy decisions for “hot button” HHR issues (1) . We propose a framework that can be used to classify, rank and evaluate HHR policy/planning documents.

Our framework creates six major criteria that are used to evaluate policy documents. These criteria are: 1) literature review, 2) source of primary information, 3) nature of recommendations, 4) implementation strategies, 5) credibility of authors and 6) credibility of publisher. Within each category, a score from zero to three (for criteria 1-4) or zero to two (criteria 5-6) is assigned, depending on the caliber of the document. Summing the scores from each section yields a document’s overall score.

The intent of this measure is two-fold. Firstly, we want to create a tool that can be widely utilized by policymakers to help inform their decisions. Secondly, it can be used as a springboard to stimulate discussion and debate around HHR planning and policy formulation.

National Information Center on Health Services Research and Health Care Technology. (NICHSR) Health Services Research and Health Policy Grey Literature Project: Summary Report. 2006. http://www.nlm.nih.gov/ nichsr/greylitreport_06.html. Accessed February 20, 2007.
23. Coley's toxin and spontaneous tumour regression
Authors: Hayre D. S.
Published: May 2017

William Coley, a young surgeon at New York Memorial Hospital, was traumatized by the loss of his first patient to bone cancer in 1891. He was unable to save this young patient and she succumbed to her Sarcoma within 3 months of surgery. He searched the hospital archive to learn more about Sarcoma and discovered the case of a patient with a large sarcoma who had undergone five unsuccessful surgeries over a 3 year period. This case had been determined to be hopeless. After the last of these operations, the patient became very ill from an erysipelas infection.

Coley was astonished to read that after the fever broke and the patient had recovered, the tumour had vanished. Seven years later, the patient was still alive and well. Coley concluded that whatever had caused the fever must also have destroyed the cancer. Coley searched for and found this patient still in excellent health. Coley reasoned that if a chance infection could make tumours vanish, then a purposefully induced infection could do the same.

The hypothesis was tested by infecting his next 10 patients with Streptococcus pyogenes to cause Erysipelas. Some of the patients were difficult to infect, some died, and some had a strong reaction and their disease regressed. Coley switched to deactivated S. pyogenes to avoid the mortality observed with the live strain. Afterxperimentation with various formulations, a combination of S pyogenes and Serratia marcescens was decided upon and became known as Coley’s Toxin.

The preferred method of delivery was injection of the toxin directly into the primary tumour or metastases in increasing doses to avoid immune tolerance. Fever response in the patient was essential to imitate a naturally occurring infection and the body’s natural response. Though Coley met with success, this therapy was abandoned as chemotherapy became more popular.

Hoption Cann SA, Gunn HD, van Netten JP, van Netten C. Dr William Coley and tumour regression: a place in history or in the future. Post Graduate Medical Journal 2003; 79:672-680.

Hobohm U. Fever and Cancer in Perspective. Cancer Immunology & Immunotherapy 2001; 50:391-396.

Grange JM, Standord JL, Stanford CA. Campbell De Morgan’s ‘Observations on cancer’, and their relevance today. Journal of the Royal Society of Medicine 2002 (June); 95:296-299.
26. Nothing but the truth, so help me God: The history of magnetic resonance imaging
Authors: Dechant A.
Published: May 2017

On the morning of October 10, 2003, the residents of New York awoke to find that an entire page of their beloved paper, The Times, had been usurped for the sole purpose of flagrant self-promotion and protestation. On his own behalf, Dr. Raymand Damadian had purchased a one page spread bemoaning his exclusion in the Nobel Prize for Medicine that year which had previously been awarded to Paul Laterbur and Peter Mansfield for their contributions to the development of Magnetic Resonance Imaging (MRI). Over the course of the next few months, the public was to witness a series of such articles proclaiming that a shameful wrong had been committed, and that the truth would eventually prove Dr. Damadian’s accusations.

That truth lay in the early theoretical and technical foundations that led to the discovery of MRI. Described just after the Second World War, nuclear magnetic resonance (NMR) was hailed as a breakthrough in physical chemistry for which Felix Bloch and Edward Purcell were awarded the Nobel Prize in Physics in 1952. Two decades later, in 1971, Dr. Damadian discovered that differences between the NMR signals of cancerous and normal tissue might provide a rapid means of cancer detection. However, Laterbur and Mansfield were the first to actually demonstrate images of live tissue using the application of magnetic gradients – the key to modern MRI.

Though speculation exists that Dr. Damadian may have been excluded from the prize due to his religious beliefs or political rivalry, only time will reveal the whole truth when the Nobel files are opened 50 years hence.

Bradley W. The Nobel Prize: Three Investigators Allowed but Two Were Chosen. Journal of Magnetic Resonance Imaging 2004; 19:520.

Laterbur P. Image formation by induced local interactions: examples of employing nuclear magnetic resonance. Nature 1973; 242:190-191.

Mansfield P, Grannell P. “NMR diffraction in solids?” Journal of Physics C: Solid State Physics 1973; 63:L433-L426.
29. The changing concept of aging and the quest for immortality
Authors: Wile D.
Published: May 2017

The desire to extend human lifespan has spurred scientific and philosophical interest back to the earliest recorded piece of human literature, the Epic of Gilgamesh, which documents the quest of a mythical king to become immortal. In the intervening years between then and now, and particularly in the last century, human lifespan has increased dramatically. Though it is commonly held that there is an upper biological limit to human lifespan, there are some who believe its recent meteoric rise can continue indefinitely.

The story of human lifespan has two largely separate prongs: that of the important advances in sanitation, agriculture and medicine that have effected the greatest change in our life expectancy, and the recurring myth, legend and popular beliefs surrounding greatly advanced or eternal human life.

In recent years, the myth and science of life expectancy have coalesced, creating a core group of people who believe that immortality is a technically achievable goal. Such claims have muddied the concept of aging such that it is now commonly described as both a disease process and a fundamental part of life.

Hackler C. Extending the life span: Mythic desires and modern dangers. HEC Forum, 2006; 16:182-196.

Holliday R. Aging is no longer an unsolved problem in biology. Ann. N.Y. Acad. Sci. 2006; 1067:1-9.

Rando TA. Stem cells, ageing and the quest for immortality. Nature 2006; 441:1080-1086.
30. Abortion and the fall of midwifery in 19th Century North America
Authors: Schram C.
Published: May 2017

The 19th Century in North America was a time of many social and scientific changes that impacted the field of medicine. A result of one such change was the medicalization of childbirth, as the primary care of women during labour shifted from midwives to physicians. While there is ample discourse on the many factors that contributed to this shift, there is very little discussion on the role played by abortion. Studying abortion in the 19th Century is often limited by a paucity of primary sources from the physicians who performed abortions and women who obtained them. Although most authors who discuss the midwifery shift do not make any mention of a role played by the issue of abortion, it has been addressed and supported by primary sources. This raises the question, why is abortion not discussed in histories on the medicalization of childbirth by other authors?

The objectives of this paper are historical and histographic. First, it will present the evidence on the use of abortion as a political tool employed by some policy makers, physicians and the media to discourage women from choosing midwives for their childbirth care. Second, it will analyze possible reasons why this topic is not addressed by the majority of historians of childbirth in 19th Century North America. Are the authors concerned about the varying social views of abortion, the associated politics, the lack of primary sources, or are they personally uncomfortable with the subject? Only the authors themselves can truly know their reasons for neglecting the subject of abortion in their work, but this analysis will show how issues that influence historians determine the version of the past that is produced and propagated into the present and the future.

Borst CG. Catching Babies: the Professionalization of Childbirth, 1870-1920. Cambridge, Mass.: Harvard University Press, 1995.

Bourgeault B, Davis-Floyd R, eds. Reconceiving Midwifery. Montreal & Kingston: McGill-Queen’s University Press, 2004.

Dodd DE, Gorham D, eds. Caring and Curing: Historical Perspectives on Women and Healing in Canada. Ottawa: University of Ottawa Press, 1994.

Wertz DC, Wertz RW. Lying In; a History of Childbirth in America (expanded edition published 1989 by Richard W. Wertz and Dorothy C. Wertz) New York: Free Press; London: Macmillan, 1977.

Reagan LJ. Linking midwives and abortion in the Progressive Era. Bulletin of the History of Medicine 1995; 69(4):569-98.

Reagan LJ. When Abortion Was a Crime, Women, Medicine, and Law in the United States, 1867-1973. London: University of California Press, 1997.
44. Publication history of the Brugada Syndrome: Did labeling stimulate research?
Authors: Nault M. A. , Baranchuk A. , Simpson C. S. , Redfearn D. P. , Abdollah H.
Published: May 2017

Sudden cardiac death (SCD) in healthy young men was first recognized in 1917. Combined with an electrocardiographic (ECG) abnormality reported in 1953, the resulting syndrome would by 1996 eventually be recognized worldwide as Brugada Syndrome (BrS).

There is evidence that “labeling” (i.e. the process of naming a disease state or ascribing a diagnosis) alters perceptions, awareness and behaviours in medicine. Our objective was to determine whether naming a cluster of signs and symptoms as a specific syndrome raised attention given to a previously recognized though poorly defined condition as evidenced through an increase in publications. We hypothesized that naming BrS resulted in such a “labeling” stimulus.

A systematic review of the Pubmed database of indexed journals was performed to identify references to BrS between 1950 and 2006. Search terms were: “Brugada Syndrome”; “Sudden Cardiac Death AND Right Bundle Branch Block”; “Bangungot” (Filipino); “Bangungut” (Filipino); “Pok kuri” (Japanese); “Lai tai” (Thai); “Sudden Unexplained Death Syndrome”; and “SUNDS”. Publications identified after 1996 by search strategies other than “Brugada Syndrome” were omitted to avoid double counting.

The search resulted in 1,042 citations. Of these, 208 occurred after 1996 and were omitted, leaving a total of 834 citations to be analyzed. Between 1950 and 1993 a total of 32 publications met the above search criteria. Thereafter, publication rate on this topic increased exponentially from 16 articles in 1994-1995 to 290 in 2005-2006.

Though numerous articles recognized either RBBB-like ECG pattern, ST segment elevation or SCD in otherwise healthy young men, it was not until publication of the 1992 Brugada and Brugada paper that the coexistence of these two conditions was recognized as a syndrome. Rising interest, as identified by publication frequency, preceded the naming of this syndrome by 4 years. This finding suggests that factors other than labeling have also contributed to the publication history of BrS.

Osher H, Wolff L. Electrocardiographic pattern simulating acute myocardial injury. Am J Med Sci 1953; 226:541-5.

Brugada P, Brugada J. Right bundle branch block, persisting ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992; 20:1391-6.

Yan G-X, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996; 93:372-9.
45. Education at distance: Broadcasting ECG rounds to Southeastern Ontario (BESO Project). An innovative approach for teaching electrocardiography
Authors: Baranchuk A. , Dagnone G. , Fowler P. , Harrison M. N. , Lisnevskaia L. , Etemadi B. , Blouin D. , Redfearn D. P. , Simpson C. S.
Published: May 2017

Electrocardiography (ECG) interpretation is an essential skill for physicians as well as for many other health care professionals. Continuing education is necessary to maintain these skills. The process of teaching and learning ECG interpretation is complex and involves both deductive mechanisms and recognition of patterns for different clinical situations (“pattern recognition”). The successful methodologies of interactive sessions and real time problem based learning have never been evaluated with a long distance education model.

To evaluate the efficacy of broadcasting ECG rounds to different hospitals in the Southeastern Ontario region; to perform qualitative research to determine the impact of this methodology in developing and maintaining skills in ECG interpretation.

ECG rounds are held weekly at Kingston General Hospital and will be transmitted live to Napanee, Belleville, Oshawa, Peterborough and Brockville. The teaching methodology is based on real ECG cases. The audience is invited to analyze the ECG case and the coordinator will introduce comments to guide the case through the proper algorithm. Final interpretation will be achieved emphasizing the deductive process and the relevance of each case. An evaluation will be filled out by each participant at the end of each session.

Videoconferencing works through a vast array of internet LANs, WANs, ISDN phone lines, routers, switches, firewalls and Codecs (Coder/Decoder) and bridges. A videoconference Codec takes the analog audio and video signal codes and compresses it into a digital signal and transmits that digital signal to another Codec where the signal is decompressed and retranslated back into analog video and audio. This compression and decompression allows large amounts of data to be transferred across a network at close to real time (384 kbps with 30 frames of video per second). Videoconferencing communication works on voice activation so whichever site is speaking has the floor and is seen by all the participating sites. A continuous presence mode allows each site to have the same visual and audio involvement as the host site. A bridged multipoint can connect between 8 and 12 sites simultaneously.

This innovative methodology for teaching ECG will facilitate access to developing and maintaining skills in ECG interpretation for a large number of health care providers.

Bertsch TF, Callas PW, Rubin A. Effectiveness of lectures attended via interactive video conferencing versus in-person in preparing third-year internal medicine clerkship students for clinical practice examinations. Teach Learn Med 2007; 19(1):4-8.

Yellowlees PM, Hogarth M, Hilty DM. The importance of distributed broadband networks to academic biomedical research and education programs. Acad Psychaitry 2006;30:451-455
52. Simulation based training improves resident competence in the performance of critical resuscitation procedures
Authors: Rigby I. , Walker I. , Donnon T. , Howes D. , Lord J.
Published: May 2017

We sought to assess the impact of procedural skills simulation training on residents’ competence in performing critical resuscitation skills. Our study was a prospective, cross-sectional study of residents from three residency training programs (Family Medicine, Emergency Medicine and Internal Medicine) at the University of Calgary. Participants completed a survey measuring competence in the performance of the procedural skills required to manage hemodynamic instability. The study intervention was an 8 hour simulation based training program focused on resuscitation procedure psychomotor skill acquisition. Competence was criterion validated at the Right Internal Jugular Central Venous Catheter Insertion station by an expert observer using a standardized checklist (Observed Structured Clinical Examination (OSCE) format). At the completion of the simulation course participants repeated the self-assessment survey. Descriptive Statistics, Cronbach’s alpha, Pearson’s correlation coefficient and Paired Sample t-test statistical tools were applied to the analyze the data.

Thirty-five of 37 residents (9 FRCPC Emergency Medicine, 4 CCFP-Emergency Medicine, 17 CCFP, and 5 Internal Medicine) completed both survey instruments and the eight hour course. Seventy-two percent of participants were PGY-1 or 2. Mean age was 30.7 years of age. Cronbach’s alpha for the survey instrument was 0.944. Pearson’s Correlation Coefficient was 0.69 (p < 0.001) for relationship between Expert Assessment and Self-Assessment. The mean improvement in competence score pre- to post-intervention was 6.77 (p < 0.01, 95% CI 5.23-8.32).

Residents from a variety of training programs (Internal Medicine, Emergency Medicine and Family Medicine) demonstrated a statistically significant improvement in competence with critical resuscitation procedural skills following an intensive simulation based training program. Self-assessment of competence was validated using correlation data based on expert assessments.

Dawson S. Procedural simulation: a primer. J Vasc Interv Radiol. 2006; 17(2.1):205-13.

Vozenilek J, Huff JS, Reznek M, Gordon JA. See one, do one, teach one: advanced technology in medical education. Acad Emerg Med. 2004; 11(11):1149-54.

Ziv A, Wolpe PR, Small SD, Glick S. Simulation-based medical education: an ethical imperative. Acad Med. 2003; 78(8):783-8.
56. Proficiency at the end of practice predicts retention of a technical clinical skills
Authors: Carnahan H. , Hagemann E. , Dubrowski A.
Published: May 2017

A debate is emerging regarding the efficacy of proficiency based versus duration based training of technical skills. It is not clear whether the performance level attained at the end of practice (i.e., proficiency criteria), or the overall amount of practice performed during learning will best predict the retention of a technical clinical skill.

The skill learned was the single-handed double square-knot. Forty two trainees learned the skill through video-based instruction and were divided into three groups (14 participants per group) each with a specific criterion time to tie the knot (10, 15, and 20 seconds). Practice continued until participants completed the knot within their criterion time. The total number of trials, and the overall practice time required to obtain each respective criterion were recorded during practice. Participants returned one-week later for a timed retention test consisting of one trial of the knot tying skill with no video instruction.

A multiple regression analysis tested whether the amount of practice, the total practice time, or the criterion reached at the end of practice was the best predictor of the time taken to perform the skill during retention. This analysis showed that the number of practice trials was highly correlated with total practice time (r = .82, p = .01), therefore total practice time was withdrawn as a predictor variable from the subsequent analysis. The regression showed that the only significant predictor of retention performance was the criterion reached at the end of practice (p = .03). The number of practice trials was not found to significantly predict the retention performance (p = .87).

The results support the notion that proficiency based training results in better retention of a technical clinical skill in comparison to duration based approaches. This provides evidence for the introduction of proficiency based educational approaches in technical skills curricula.

Jowett N, LeBlanc V, Xeroulis G, MacRae H, Dubrowski A. Surgical skill acquisition with self-directed practice using computer-based video training. Am J Surg. 2007; 193(2):237-42.

Gallagher AG, Ritter EM, Champion H, Higgins G, Fried MP, Moses G, Smith CD, Satava RM. Virtual reality simulation for the operating room: proficiency-based training as a paradigm shift in surgical skills training. Ann Surg. 2005; 241(2):364-72.

Van Sickle KR, Ritter EM, McClusky DA, Lederman A, Baghai M, Gallagher AG, Smith CD. Attempted establishment of proficiency levels for laparoscopic performance on a national scale using simulation: the results from the 2004 SAGES Minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR) learning center study. Surg Endosc. 2007; 21(1):5-10.
57. The power of power: Comparative evaluations of medical residency training across teaching sites and programs at the University of Torontos
Authors: Abrahams C. , Verma S. , Muharuma L. , Imrie K. , Vestemean R. , Poldre P. , McIlroy J. , Woods N.
Published: May 2017

To meet accountability and accreditation requirements, teaching partners and the faculty postgraduate office required more robust and integrated feedback on teaching and assessment. The web-based evaluation system known as POstgraduate Web Evaluation and Registration (POWER) was implemented in 2004/05 by most residency training programs, using their existing forms and scoring scales. At start up, over 250 different evaluation forms and 85 varying scoring scales were in operation across programs for the In-Training Evaluation Reports (ITERs) and resident-completed evaluations for Rotation Evaluation Scores (RES) and Teaching Effectiveness Scores (TES).

The POWER Evaluation Working Group was formed to develop a methodology to gather and consolidate evaluations to report on medical residents, their teachers, and rotations in a clear, consistent user-friendly format, map general questions against CanMEDS roles and Family Medicine principles, and convert all scoring scales to a consistent 5 point Likert scale. A standardized naming protocol was developed to map rotation services to individual teaching sites.

The 2004/05 analysis of these evaluations (2004/05 Annual POWER Report: Lessons Learned) provide baseline data to begin monitoring trends in resident and faculty performance, assess the quality of programs and identify areas for improvement by CanMEDS standards and CFPC principles. Mean scores, standard deviations and number of evaluations were presented by teaching site and program.

Consolidation of evaluations by program and teaching site provides valuable feedback to hospitals and programs wishing to standardize and improve their assessment systems, and to postgraduate medical offices who must maintain evaluation standards and illustrate trends for accreditation purposes. Future activities include: standardizing evaluation forms starting July 2007, improving scoring consistency and accuracy, improve participation rates and timeliness of responses, develop a procedure/case log tracking system, and trend analysis.

Afrin LB, Arana GW, Medio FJ, Ybarra AF, Clarke HS Jr. Improving oversight of the graduate medical education enterprise: one institution’s strategies and tools. Academic Medicine 2006 (May); 81(5):419-25.

Benjamin S, Robbins LI, Kung S. Online Sources for assessment and evaluation. Academic Psychiatry 2006 (Nov-Dec); 30(6):498-504.

Rosenberg ME, Watson K, Paul J Miller W, Harris I, Valdivia TD. Development and Implementation of a web-based evaluation system for an internal medicine residency program. Academic Medicine 2001 (Jan); 76(1):92-5.
62. Does an expert presentation raise awareness of CanMEDs Roles among residents?s
Authors: Jenkins S. , Crocker K. , Jeon P. , Borgaonkar M. , Pace D. , Verma S.
Published: May 2017

We set out to determine whether an expert presentation on CanMEDS would raise awareness of CanMEDS roles among residents. We addressed this question with paired surveys distributed before and after the expert presentation.

Each survey outlined seven different clinical scenarios each of which required one of the seven core CanMEDS competencies. Paired surveys were distributed prior to the presentation to the audience that was composed of a selection of residents from various disciplines. One survey was filled out prior to and the second survey completed following the expert presentation.

Data were analysed using nonparamentric statistical methods. There was in general, a low pre-presentation background knowledge of CanMEDS roles, with wide variability between specialties. Our hypothesis that disciplines with less patient contact would have less understanding of CanMEDS roles was not fully supported. All specialties demonstrated improvement in their understanding of CanMEDS roles in the post-presentation survey.

While there is a low background level of knowledge about CanMEDS roles, we determined that following an expert presentation (in this case by Dr. Serita Verma) the residents were significantly more able to correctly apply the core competencies of the CanMEDS model to the given clinical scenarios. We propose that an expert presentation could be applied as an innovative educational tool advancing CanMEDS education among residents.
64. International child health (ICH) education in Canadian paediatric residency programss
Authors: Audcent T. , MacDonnell H. , Brenner J. , Samson L.
Published: May 2017

A national survey was conducted of current ICH exposure and curriculum in pediatric residency programs. Our objectives were to quantify ICH teaching presently occurring, to identify how programs support trainees in undertaking ICH electives during their training, to determine attitudes towards ICH amongst paediatric program directors and chief residents across the country, and to identify barriers to ICH curriculum expansion within the post-graduate programs.

A population census of all 44 chief residents and program directors from the 16 Canadian pediatric programs was undertaken. A self-administered survey was developed de novo for this study. Twenty-two qualitative and quantitative questions were developed under the following domains: demographics, program content, electives, attitudes and perceptions, barriers and future directions. Surveys were completed electronically. Descriptive statistics were used, and common themes were extracted from qualitative responses.

The response rate was 65% (29 surveys), with 81% of the training programs represented. Seventy-three percent of the program directors, and 44% of the chief residents from across the country responded. Eighty-nine percent reported that their program did not have a formal curriculum in ICH. All respondents reported some ICH related educational sessions, however certain areas felt to be key were lacking. 80% agreed that electives should be encouraged as part of residency training, but 72% indicated lack of adequate funding for these electives. Overall, 86% agreed that ICH issues are important for paediatric trainees and 84% indicated that more emphasis should be placed on ICH in the paediatric resident curriculum. Eighty-six percent of respondents agreed that their program would be interested in new initiatives regarding ICH.

The results of this survey demonstrate that although there are opportunities for ICH exposure in most paediatric training programs, formalized curriculum is lacking. The majority of programs indicated a willingness to support the integration of an ICH curriculum into their core educational components.

The Association of Faculties of Medicine of Canada (AFMC). Towards a Medical Education Relevant to All : The Case for Global Health in Medical Education. A Report of the Global Health Resource Group. April 2006.

Bateman C, et al. Bringing global issues to medical teaching. Lancet, 2001; 358:1539-42.

Edwards R, et al. Understanding global health issues: are international health electives the answer? Medical Education, 2004; 38:688-690.
74. Remediation plans: Effectively matching trainee needs to remediation planss
Authors: Takahashi S. Glover , Martin D. , Verma S. , Edwards S.
Published: May 2017

This paper is a retrospective study reporting on the development of remediation plans for residents who are having difficulty meeting the established program goals and objectives. Additionally, the paper describes the implementation of a consistent, competency focused approach to remediation using a standardized needs assessment and intervention planning tool has functioned to better manage difficulty. First, the paper provides a profile of the educational needs of 20 recent cases describing their specialty programs, training levels and the competency areas of difficulty. Next the paper outlines an educational inquiry tool used by residency program directors to develop, implement and evaluate the trainee’s remediation programs. The tool includes inquiry questions which the faculty answer in the development of a customized remedial educational plan in the such areas as: trainee background, trainee information, overall rationale for remediation plan, training profile, purpose of remediation, details of remediation plan, anticipated outcome of remediation plan, other factors impacting trainee success. The tool is designed to be reviewed with trainee input to ensure the desired outcomes and process for the remediation plan are transparent for both the trainee and program director. Finally three case studies are described in detail including of the types of problems that lead to remediation, examples of the remediation plans developed and the range of approaches employed to support the success of residents. The paper then summarizes the identified key issues and options in optimizing success for residents in difficulty.

Christopher I, Doty CI, Lucchesi M. The Value of a Web-based Testing System to Identify Residents Who Need Early Remediation: What Were We Waiting For? Acad Emerg Med 11(3):324.

Beeson MS, Jwayyed S. Development of a Specialty-wide Web-based Medical Knowledge Assessment Tool for Resident Education. Acad. Emerg. Med 2004 (Mar); 11(3):324.

Boiselle PM. Remedy for Resident Evaluation and Remediation, Academic Radiology 2005(July); 12(7):894-900.
Profiling YB-1 responsive genes in basal-like breast cancer cells by ChIP-on-chip reveals direct binding to PIK3CAs
Authors: Astanehe A , Finkbeiner M
Published: May 2017

Purpose: Basal-like breast cancers (BLBC) are typically very aggressive and they are also prone to a high rate of recurrence. We recently identified the transcription factor Y-box binding protein-1 (YB-1) as an important component of BLBC by screening breast tumour tissue microarrays. YB-1 is well known for its ability to confer chemotherapy resistance and to promote the growth of a wide range of cancer cell types. The breast cancer cell line SUM149 was characterized by us as having all the hallmarks of BLBC including a lack of the estrogen, progesterone, and Her-2 receptors. We also find that they express high levels of the epidermal growth factor receptor, a YB-1 responsive gene.

We performed a genome-wide promoter screen of the possible YB-1 responsive genes using the NimbleGen ChIP-on-chip (COC) platform to begin to understand how this oncogene regulates the growth of basal-like breast cancer cells. YB-1 was found to bind to ~6,700 human promoters. Several members of the phosphatidylinositol-3-kinase (PI3K) pathway were identified (p110a, p85, Akt-2, ILK). Of particular interest was the identification of PIK3CA, the gene that codes for the p110a catalytic subunit of PI3K. PI3K, a lipid kinase with important roles in neoplasia, phosphorylates membrane inositol lipids resulting in activation of downstream effectors that are involved in cellular responses such as cell proliferation, survival, metabolism, and cytoskeletal reorganization. Many studies have suggested importance of the role of PI3K signaling in various types of cancer. Approximately 20% of breast cancers harbour somatic activating mutations in PIK3CA, and about 8% have amplification of PIK3CA. The remainder of the cancers have elevated levels of PI3K via other mechanisms including increased transcription.

Methods & Results: Here we propose that YB-1 overexpression in cancer leads to increased PIK3CA transcription via direct binding to the promoter. To extend our COC findings, we knocked down YB-1 with siRNA and observed a concomitant loss in p110a by immunoblotting. We have recently identified two alternate PIK3CA transcriptional start sites (exon 1a and 1b) and two alternate PIK3CA promoters (promoter 1a and 1b). We mapped potential YB-1 binding sites on PIK3CA promoters 1a and 1b, and identified five putative YB-1 binding sites within promoter 1a and one putative binding site within promoter 1b. We further performed traditional ChIP and EMSA to confirm the interaction of YB-1 with the putative binding sites on PIK3CA promoter, and determined that YB-1 binds to promoter 1a, but not to promoter 1b.

Conclusion:The demonstration that YB-1 binds directly to the PIK3CA promoter and induces its activity identifies a novel mechanism whereby activation of YB-1 and subsequent up-regulation of PIK3CA may contribute to the pathophysiology, outcomes and therapeutic responsiveness of breast cancer.
Molecular characterization of the development of the K65R and M184V drug resistance mutations in Subtype C HIV-1s
Authors: Coutsinos Dimitrios , Invernizzi Cédric F. , Moisi Daniela , Oliveira Maureen , Brenner Bluma G. , Wainberg Mark A.
Published: May 2017

Background: We have shown that the K65R mutation is selected more rapidly in subtype C than in subtype B HIV-1 isolates in both cell culture and clinical studies. Biochemical comparisons between subtype B and C-derived reverse transcriptase (RT) enzymes revealed similar molecular characteristics that do not explain the more rapid selection of K65R with subtype C viruses. This study attempts to establish the mechanistic basis for the difference.

Methods: Recombinant subtype C and B HIV-1 RT enzymes were expressed and purified in E. coli. Gel-based nucleotide extension assays were used to study DNA synthesis from various natural and synthetic DNA and RNA templates that spanned regions of the pol gene responsible for the K65R and M184V mutations. Cell based experiments were performed using MT2 cells infected with mutated subtype B HIV-1 pNL4-3 viruses.

Results: The propensity for the more rapid selection of K65R with subtype C enzymes is due to the mechanism of DNA synthesis from a subtype C template. The use of templates containing the 64, 65 and 66 codons of the pol gene led to different patterns of DNA synthesis. When subtype C RT was employed to synthesize DNA from subtype C templates, preferential pausing was seen at the nucleotide position responsible for the AAG to AGG mutation on codon 65 which gives rise to K65R. In contrast, the use of subtype B RT together with a subtype B template reveals a different pattern of DNA synthesis. When subtype B RT was employed with a subtype C template, DNA synthesis stopped at the exact nucleotide position responsible for K65R. This phenomenon was not observed when subtype C RT was used with a subtype B template. A similar method was employed to investigate if differences exist in the appearance of M184V between subtypes. The results suggest that M184V is not favoured due to its coding sequence and that the propensity for the development of M184V remains the same in subtype B and C HIV. In cell culture, K65R was detected faster in subtype B that has been mutated to include the 64/65 codons of subtype C, when compared to wild-type subtype B HIV.

Conclusions: The more rapid emergence of K65R but not M184V in subtype C RT appears to be based on the pol gene coding sequence. These results urge for the analysis of resistance mechanisms to be studied in all HIV subtypes separately and have clinical relevance in regard to the management of subtype C infections.
Elucidating the role of P63 during development of the mammalian nervous systems
Authors: Dugani Sagar , Paquin Annie , Kaplan David R. , Miller Freda D.
Published: May 2017

Background: The protein p63, a recently discovered member of the p53 family of proteins, is implicated in the maintenance and differentiation of stem cells in the epidermis and is involved in the regulation of naturally-occurring cell death in sympathetic neurons of the peripheral nervous system. Since initial data from our laboratory indicated that p63 is also widely expressed in stem cells and neurons within the developing brain, we assessed its involvement in regulating the genesis and survival of developing cortical neurons. As neurogenesis is initiated at embryonic day 12 (E12), we isolated cortical precursors from p63-/- embryos at E14 and cultured them for 2 days in vitro (DIV).

Methods: Based on immunocytochemistry to known markers of apoptosis and neurons, we assessed the level of cell death and neurogenesis.

Results: Compared to p63+/+ cortical precursors, p63-/- precursors from littermates showed a 50 % reduction in neuronal death, as assessed by the apoptosis marker, cleaved caspase 3. Interestingly, the proportion of neurons and astrocyte precursors, the latter identified by S100b was also reduced in p63-/- embryos, as compared to p63+/+ littermates.

Conclusions: These results suggest that p63 may be involved in the regulation of cell survival and in the differentiation of precursors into neurons and astrocytes. To assess the former, we overexpressed TAp63a, a full-length isoform of p63, in E12/13 cortical precursors and assessed the level of cell death after 2 DIV. Compared to control cells, cells transfected with TAp63a demonstrated a 2-fold increase in cell death. Ongoing work will characterize p63 involvement in differentiation of precursor cells into neurons and astrocytes. To assess if these findings are relevant in vivo, we will use p63flox,flox X Nextin-Cre mice, which have p63 specifically ablated in neural precursors. We will analyze the survival, proliferation, and fate of these p63-/- cells. Together, these studies will help to determine a role for p63 in neural proliferation and apoptosis, processes central to development and response to injury.
The role of CRMP4 in nerve regenerations
Authors: Tone Stephan Ong , Alabed Yazan Z. , Fournier Alyson E.
Published: May 2017

The inability of CNS neurons to regenerate and reform functional connections following spinal cord injury has devastating clinical consequences. The failure of CNS neurons to spontaneously regenerate following injury can be partially attributed to the expression of neurite outgrowth inhibitory myelin associated inhibitors (MAIs). MAIs signal through a tripartite receptor complex to activate the cytosolic protein RhoA and influence cytoskeletal dynamics. RhoA antagonists promote neuronal survival and regeneration in animal models of nerve injury. However, RhoA's potential as a therapeutic target may be limited by its widespread roles in multiples cellular processes and cell types. In an attempt to discover more specific therapeutic targets to promote nerve regeneration, our lab identified the cytosolic phosphoprotein CRMP4b (Collapsin Response Mediator Protein 4b) as a protein that functionally interacts with RhoA to mediate neurite outgrowth inhibition. siRNA-mediated knockdown of CRMP4 and blockade of the RhoA-CRMP4b interaction with a competitive peptide (C4RIP) attenuates myelin-dependent neurite outgrowth inhibition. Analysis of the proximal tip of extending axons (growth cones) by time lapse video microscopy reveals that C4RIP regulates filopodial dynamics indicating that C4RIP modulates the actin cytoskeleton. We are currently investigating the in vivo roles of CRMP4 in regeneration in an optic nerve injury model by developing readily deliverable C4RIP and a CRMP4 knockout mouse. Elucidating the role of CRMP4 in nerve regeneration may provide insight into the molecular mechanisms following nervous system injury.
An analysis of the adaptive immune response towards an embryonic stem cell grafts
Authors: Wu Douglas , Wood Kathryn
Published: May 2017

Background: Although clinical transplantation has had enormous impact on the treatment of premature organ failure, shortage of donor organs continues to be a crucial limiting factor. Embryonic stem cells represent an attractive potential source of replacement tissue because of their inherent pluripotentiality and ability to self-renew. However, before any ES cell-based cellular replacement strategies can be considered, many issues must be addressed. Among these is an evaluation of the potential immune response elicited by any ES cell graft. Because ES cells express very low levels of MHC class I and no MHC class II, their immunogenicity has been questioned. Here we utilize a BM3 TCR transgenic model to analyze the adaptive immune response against an ES cell graft in vivo.

Methods: BM3 CD8 TCR-tg T cells (H2K background) specific for the MHC class I molecule H2Kb were labelled with CFSE and adoptively transferred into CBA rag recipients. The following day, ES cells derived from a CBA, B6, or CBK background were implanted beneath the kidney capsule of adoptively transferred mice. Response of the CD8 T cells was measured via CSFE division profiling and graft infiltration.

Results: CFSE division profile of naïve BM3 CD8 T cells was unaltered by the presence of either a syngeneic or an allogeneic ES cell graft. These naïve cells were also unable to recognize and infiltrate either a syngeneic or allogeneic ES cell graft on days 5 and 10 post-implantation, despite strong expression of the MHC class I molecule H2Kb by engrafted allogeneic ES cells. On the other hand, H2Kb+ islets begun to be infiltrated by day 5, and were obliterated by a vigorous allogeneic response by day 10. When H2Kb+ islets were implanted into the same kidney as allogeneic ES cells (opposite poles), islet grafts were rapidly infiltrated by CD4 and CD8 T cells and destroyed, but ES cell grafts exhibited markedly reduced cellular infiltrate. In contrast to naïve BM3 CD8 T cells, however, activated cells recognized and mounted an aggressive cytotoxic response against an allogeneic ES cell graft which could be detected by day 6 and resulted in complete graft destruction by day 10.

Conclusions: Under certain circumstances, an ES cell graft may have reduced immunogenicity as compared with other conventional tissue or solid organ allografts. This may be due to their lack of passenger APC, which may in turn cripple their ability to elicit a robust allogeneic response via the direct pathway of allorecognition. However, because of their strong upregulation of allogeneic MHC class I molecules after transplantation, they are still likely to elicit a significant rejection response when transplanted into recipients replete with both CD4 and CD8 T cells.