Session Descriptions 2017

Sunday April 30, 2017

Bev Heim-Myers

Title -  Bill S201- The Journey towards genetic fairness in Canada

Objectives:

At the end of the session, the participants will be able to:

  • Understanding the history of protecting genetic information in Canada and Bill S20
  • Understanding the legislative process, the stakeholders that helped make it happen and how Bill S201 works to protect genetic test information in Canada

Monday May 1, 2017

Anne Bassett

Title -  Pathogenic CNVs, the adult phenotype, and counselling about long term outcome

Objectives:

At the end of the session, the participants will be able to:

  • Appreciate the important role of counselling about the adult phenotype of pathogenic copy number variations for individuals at different life stages
  • List three treatable conditions usually arising in adulthood associated with at least two different pathogenic CNVs
  • Describe potential benefits of genetic diagnosis for patients with schizophrenia, their families, and their clinicians

Description:

Available knowledge about the adult phenotype has been limited for many recurrent rare CNVs but is gradually accumulating, particularly about the importance of variable neuropsychiatric expression. In this session, up-to-date data for the most commonly occurring of these pathogenic CNVs will be reviewed and key questions and issues addressed. These will include: What is known so far about the lifetime implications of these CNVs, particularly the long term adult phenotype? What is known about the expected long term outcomes? How does genetic counselling differ for adults newly diagnosed with a pathogenic CNV, including transmitting parents, compared with counselling about adult expectations and relevant risks for the prenatal and paediatric populations? What are the implications of non-invasive (e.g., cell-free DNA) prenatal screening tests? While the focus will be on neuropsychiatric / neurodevelopmental phenotypes, pertinent long term medical genetic issues, including reproductive fitness, will be included.

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Melissa Carter

Title -  The joy and pain of genetic counselling for recurrent CNVs implicated in neurodevelopmental disorders

Objectives:

At the end of the session, the participants will be able to:

  • Discuss the differences between a "syndrome" and a "susceptibility variant" with respect to recurrent CNVs
  • Understand one's own biases, and those in the case report literature, regarding these CNVs
  • Identify the gaps in the current evidence base for the pathogenic nature of these CNVs
  • Share ideas about how to counsel our patients in the absence of certainty

Description:

The more "seasoned" clinicians among us will remember the excitement of ordering our first chromosomal microarrays (CMA) for our patients. Ten years on, we can all empathize with the myriad complexities of counselling parents regarding the clinical implications of certain recurrent CNVs for their children. Now that prenatal CMA is widely used, the implications of our counselling is ever more fraught with uncertainty, and the stakes are high. In this session, the speaker will explore the changing face of CNV interpretation in the clinic. We will discuss the concepts of "syndrome" versus "susceptibility variant" and offer (hopefully) helpful tips for counselling. Using 15q11.2 microdeletion and 22q11.2 duplication as examples, we will explore how the case report literature biases our counselling, and identify our own biases for what constitutes "normal."

This session will be of interest to Medical Geneticists, cytogenomicists, and trainees at all levels of training.

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Sébastien Jacquemot
Melissa Carter

Title -  Gene Dosage effects on cognition and additive/oligogenic models in the neurodevelopmental clinic

Objectives:

At the end of the session, the participants will be able to:

  • Understand the heritability of cognitive and behavioral traits
  • Understand the quantitative effects of genomic variants on cognitive and behavioral traits
  • Use available data to understand the contribution of genomic variants to the symptoms present in patients referred for a neurodevelopmental disorder.
  • Understand the implication of these studies on genetic counselling

Description:

Neurodevelopmental disorders including intellectual disabilities, severe learning disabilities, autism spectrum disorder and represent a significant health burden. With the routine implementation of whole genome chromosomal microarrays (CMAs) in the neurodevelopmental clinic, “clinically significant CNVs are currently identified in 10 to 15 % of children with NDs. The rate of “clinically significant” variants will continue to increase with the routine implementation in the near future, of next generation sequencing.

However, the effects of CNVs on essential cognitive and behavioral dimensions (i.e. general intelligence, social cognition, language, emotional regulation) have been studied in only a small number of these variants.

We will discuss results from our research group and others using cohorts of individuals who carry the same genomic variant to study their impact on quantitative cognitive traits. These approaches are effective, but currently, are not scalable to all genomic variants. Most “clinically significant” CNVs are “non-recurrent” and we will discuss strategies investigate this category of genetic variants.

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Christian Marshall

Title - Copy Number Variants in Neurodevelopmental Disorders

Objectives:

At the end of the session, the participants will be able to:

  • Differentiate between recurrent and non-recurrent copy number variants and identify the mechanisms that lead to their formation.
  • Describe the strategies used for interpretation of copy number variants including the criteria used to establish clinical significance.
  • Identify the most common CNVs associated with neurodevelopmental disorders.

Description:


The advent of chromosome microarray analysis (CMA) revealed that copy number variation (CNV) is a major etiology for those with diagnosed with neurodevelopmental delay. CMA has been widely adopted as the first tier clinical test for these disorders with many of the causative CNVs being recurrent. This session will provide an overview of CNVs in neurodevelopmental disorders including a historical perspective on their discovery up to the latest catalogue of clinically relevant CNVs. Strategies used to establish CNV pathogenicity, including rarity, case-control prevalence, phenotypic assessment and segregation with phenotype will also be discussed. Future directions, including the implementation of higher resolution scanning technologies and their implications for CNV identification will also be discussed.

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Grant Mitchell
Jean-Francois Soucy
Julie Gauthier

Title - Molecular Diagnostics in the Integrated Approach to Mitochondrial Disease

Objectives:

At the end of the session, the participants will be able to:

  • Explain the differences in molecular diagnostics of diseases due to mitochondrial DNA mutations and those due to nuclear DNA mutations. Summarize the criteria for assigning the
  • pathogenicity of nuclear mutations in mitochondrial disease.
  • Explain the importance of tissue heteroplasmy in determining the phenotype of diseases of mitochondrial DNA.
  • Discuss the use of molecular diagnosis with respect to clinical and biochemical evaluations of the patient and of patient samples.

Description:

Mitochondrial diseases can be caused by mutations in nuclear or in mitochondrial DNA. Clinical, pathological, biochemical and molecular evaluations can each provide key elements in the diagnosis of mitochondrial disease. We will briefly list the particularities of mitochondrial diseases, describe an integrated approach to the diagnosis of mitochondrial disease and then focus on the experience of our molecular diagnostic laboratory with the development of mitochondrial DNA analysis and of exome sequencing for the diagnosis of mitochondrial disease, providing clinical illustrations

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Patrick MacLeod

Title - Neurodegeneration when iron is the culprit

Objectives:

At the end of the session, the participants will be able to:

  • Summarize the biology of iron metabolism
  • Discuss the role of iron in the brain
  • Discuss the various forms of neurodegeneration with brain iron accumulation
  • List the genes involved in NBIA

Description:

This session will review the basic elements of iron biology and biochemistry with emphasis on the various genetic causes of abnormal iron accumulation, specifically those related to a newly described group of conditions where there is Neurodegneration with Brain Iron Accumulation(NBIA). I will present a recent case involving a young 25 year old student presenting with signs of dystonia and parkinsonism and our efforts to treat him with an iron chelating agent over a period of 38 weeks followed by a year long trial with various antioxidant products to address the disruption of mitochondrial biochemistry due to iron accumulation.

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Nancy Braverman

Title - Peroxisome biogenesis disorders and related single enzyme defects: clinical updates and pre-clinical approaches to targeted therapies.

Objectives:

At the end of the session, the participants will be able to:

  • Integrate newly described peroxisome disorders
  • Formulate a diagnostic model for the different peroxisome disorders
  • Describe new contributions to peroxisome biology
    Appraise preclinical approaches to therapy

Description:

The peroxisome biogenesis disorders are grouped into two classes- Zellweger spectrum disorder and rhizomelic chondrodysplasia punctata spectrum. These conditions have recently undergone extensive updating, reflecting new knowledge in terms of the clinical spectrum (including atypical presentations), the identification of individuals with normal intellect, and the recognition that this is both a pediatric and adult condition. Related peroxisome single enzyme defects clinically mimic the peroxisome biogenesis disorders, and need to be included in a differential diagnosis. Routine biochemical screening has limitations in individuals with milder disease. With the advent of next generation sequencing, presentations of traditional PEX gene defects has changed dramatically and new genes have been identified that cause these disorders. Added to this, is novel findings in peroxisome biology that illuminate additional roles for peroxisomes in health and disease.

Overall, this remains a multisystem disease requiring a complex care approach. Natural history studies to provide physicians and caretakers with more accurate management guidelines are being done. Given that the majority of patients with Zellweger spectrum disorder do not have congenital abnormalities (found only in severe Zellweger syndrome) and have a progressive disorder of peroxisome dysfunction over time, there is a window of opportunity to intervene and improve the course of this disease. There is more imperative now than ever, to identify potential therapies, as newborn sreening for elevated very long chain fatty acids was added to the uniform newborn screening panel in the USA. Preclinical investigations for targeted therapies in Zellweger spectrum disorder and rhizomelic chondrodysplasia punctata will also be discussed.

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Eric Shoubridge

Title - Mitochondrial Diseases: Whole exome sequencing and beyond

Objectives:

At the end of the session, the participants will be able to:

  • maximize success of finding genetic defects by WES
  • validate variants of unknown significance
  • use modern tools for interrogating mitochondrial interactomes

Description:

I will give an overview of the application of WES to the discovery of the genetic causes of mitochondrial diseases. I will also present the methods I think are most useful for the biochemical workup of such patients before proceeding with WES, and the techniques available, and pitfalls, in validation of the pathogenicity of new mutations in unknown or known genes. Finally I will briefly discuss a tool which allows us to place uncharacterized proteins in a pathway and investigate how pathogenic variants lead to changes in their interactomes. This session should be of value to medical geneticists and trainees.

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Tuesday May 2, 2017

Dr. Diane Allingham-Hawkins

Title - Finding Answers: Comprehensive Fetal and Neonatal Loss Panel

Objectives:

At the end of the session, the participants will be able to:

  • By the end of this seminar, participants should be able to:
  • Discuss the incidence and major causes of miscarriage, stillbirth, and neonatal death. 
  • Describe the major genetic contributors to miscarriage, stillbirth, and neonatal death.
  • Explain the benefits and limitations of genetic testing in cases of miscarriage, stillbirth, and neonatal death.

Description:

Dr. Diane Allingham-Hawkins is a Laboratory Director at PreventionGenetics, LLC, in Marshfield, WI. She is dual-certified in molecular genetics and cytogenetics by the Canadian College of Medical Geneticists (CCMG). Dr. Allingham-Hawkins earned her BSc in Honors Genetics from the University of Western Ontario in 1987 and her PhD from McMaster University in 1993. She completed her post-doctoral fellowship in Molecular Genetics at the Hospital for Sick Children in Toronto, Canada in 1995. Prior to joining PreventionGenetics, Dr. Allingham-Hawkins was a private genetics laboratory consultant from 2015 to 2016 and Senior Director of Genetic Test Evaluation and Technical Editing at Hayes, Inc. from 2008 to 2015.

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Anne Marie Laberge

Title - The Importance of Peace of Mind: Lessons Learned from the Evaluation of a Community-based Carrier Screening Program in First Nations Communities

Objectives:

At the end of the session, the participants will be able to:

  • Describe the carrier screening program for Cree encephalitis and Cree leukoencephalopathy in the Cree communities of James Bay
  • Discuss the importance of adapting a program to the target population's needs and values
  • Use the lessons learned in this setting to their own practice when counseling individuals and couples about carrier screening for recessive conditions

Description:

Cree Encephalitis (CE) and Cree Leukencephalopathy (CLE) are severe neurodegenerative autosomal recessive diseases with high carrier rates in the James Bay Cree communities. A population-based education and carrier screening program (ECSP) was developed by the Cree Board of Health and Social Services of James Bay (CBHSSJB), in collaboration with a community family support group (Eeyou Awaash Foundation; EAF). The ECSP offers education/counseling sessions and carrier screening to high school students (≥ 14 years), and women of reproductive age and their partners.

In collaboration with the CBHSSJB and the EAF, we evaluated the ECSP through: 1) qualitative analysis of interviews with couples who participated in the ECSP, 2) retrospective evaluation of program outcomes, 3) prospective assessment of participant knowledge and satisfaction, 4) assessment of health care providers’ knowledge and attitudes about the ECSP.

Participants are highly satisfied. They feel the program is important for the community, articularly so that carrier couples have the opportunity to prepare for having a child with CE or CLE. Uptake of prenatal diagnosis in carrier couples is high. Participants’ knowledge improved after screening and remained better 6-12 months later. Recall of carrier status is also high 6-12 months later. We continue to work closely with the CBHSSJB and the EAF, and our findings are used to improve the program. Our findings highlight the importance of adapting carrier screening programs to the values and needs of the target population. We hope our work will inform the development of population-based carrier screening programs, particularly in First Nations communities.

The session will be of value to: Medical Geneticists, Trainees, Genetic counselors.

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Simon Gravel
Soheil Baharian

Title - The Great Migration and African-American genomic diversity

Objectives:

At the end of the session, the participants will be able to:

  • Describe how recent history affected genomic diversity
  • Build models of genetic admixture
  • Build models of genetic relatedness

Description:

Present-day Canadian populations are the result of dramatic migration flows, from the crossing of Beringia by the first settlers over 10,000 years ago to colonial settlements, slave trade, and post-colonial migrations. Understanding the impact of such migrations on genomic diversity in populations across the Americas helps understand our history, and ensure that medical genetics discoveries can be applied to all Canadians -- not just those of European descent. 

To begin this effort, we present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of 1516km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance.

We discuss consequences of these models and findings on the genetics of Canadian populations.

 

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Victoria Sui

Title - High tech in a low tech world: The provision of culturally sensitive genetics healthcare to the Amish and Mennonite population in southwestern Ontario.

Objectives:

At the end of the session, the participants will be able to:

  • Discuss the importance of cultural competency in working with Anabaptist groups
  • Summarize resources available for diagnosis and management of genetic disorders in this population
  • Discuss the outcomes of a targeted newborn and carrier screening program

Description:

Southwestern Ontario is home to several Old Order Amish, Old Order Mennonite, and Low German-speaking Mennonite communities. This presentation will demonstrate how an understanding of the history and traditions of these different groups can facilitate the provision of culturally sensitive healthcare to families. The evolution of a newborn screening program for treatable genetic disorders will be described, along with several unique syndromes. Finally, the Amish, Mennonite, and Hutterite genetic database will be presented. This session will be of value to medical geneticists, cytogeneticists, biochemical geneticists, molecular geneticists, family physicians and specialists as well as trainees.

 

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Cheryl Rockman-Greenberg & Elizabeth Spriggs

Title - From Gene Discovery to Provision of Genomic Medicine in the Hutterite Population

Objectives:

At the end of the session, the participants will be able to:

  • Name at least 3 autosomal recessive diseases unique to Hutterites where the mutations are known.
  • Define what the “Hutterite Chip” is and its main role in diagnostics.
  • Describe the molecular technology behind the “Hutterite Chip”.
  • Assess the pros and cons of implementing a “Hutterite Chip” into medical practice.
  • Discuss the ethical concerns.

Description:

The Hutterites are a religious isolate living in colonies across the North American prairies. This population originated from approximately 90 founders, resulting in a number of genetic diseases that are over-represented, under-represented or unique. The founder effect in this population increases the likelihood that Hutterite couples carry the same recessive mutations. Manitoba Hutterites closely worked with members of the Winnipeg Genetics team and together we communicated to the Hutterite colonies the option of carrier screening for these disorders. With strong support of the elders and the Hutterite communities, we proceeded with the creation of a diagnostic chip. This was developed with Asper Biotech on a fee-for-service basis. Mutations selected for inclusion were limited to those leading to autosomal recessive disorders, maintaining its primary use as a test for determining carrier status. The DNA chip was developed to detect 32 disease-causing mutations in 30 genes and validated using controls. The chip successfully detected carrier status for 30 variants. Two variants proved difficult to conclusively determine zygosity, a duplication causing restrictive dermopathy and a large 290 kb deletion leading to VLDLR-associated cerebellar hypoplasia. While the chip is a sensitive and specific means of carrier testing for multiple disease-causing variants in the Hutterite population, its uptake and utility remain to be determined. The session will be of value to: Medical Geneticists, Laboratory Geneticists, and Trainees.

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Rosanna Weksberg

Title - The Power of Genome-Wide DNA Methylation: A Functional Tool for Classifying Mutations

Objectives:

At the end of the session, the participants will be able to:

  • Describe epigenetic marks and their role in normal development and in the pathophysiology of genetic disorders
  • Identify a range of human syndromes caused by mutations in epigenetic regulators or epigenes
  • Describe how functional epigenetic studies could be used to classify variants of unknown significance

Description:

Recent advances in genomic research have rapidly enhanced our understanding of the molecular basis of many human neurodevelopmental disorders. Elucidation of the genetic etiology of such disorders has already identified more than 60 genes involved in regulating epigenetic mechanisms (epigenes). We have identified highly specific and highly sensitive genome-wide DNAm signatures for more than10 epigenes including NSD1, EZH2/EED, CHD7, KMT2D, and KMT6A, CHD8, and DNMT1 associated with Sotos, Weaver, CHARGE, and Kabuki syndromes, autism and neurodegeneration respectively. These DNAm signatures that are highly sensitive and specific (>95%), can be used to classify sequence variants of unknown significance (VUS) as either benign or pathogenic with efficacy far superior to most in silico tools used in DNA diagnostics. We have also shown that the gene-specific DNAm signatures reflect the functional pathophysiology of the associated genetic disorders and propose that these DNA methylation signatures could be used to identify potential therapeutic targets and, in future, for first tier molecular diagnostics.

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Wednesday May 3, 2017

 

Title - Medical Humanities and Narrative Symposium

The care of the sick unfolds in stories. The effective practice of healthcare requires the ability to recognize, absorb, interpret, and act on the stories and plights of others. Medicine practiced with narrative competence is a model for humane and effective medical practice.—Rita Charon, Program in Narrative Medicine, Columbia University

This symposium will introduce the concepts of narrative medicine and its use in medical practice and education

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Joyce Zazulak

Title - Seeing Ourselves and Others: Developing Empathic Future Medical Leaders through Visual Art.

Objectives:

  • Understand of the role of the arts in medical education
  • Demonstrate the role of the arts in development of empathetic and compassion healthcare providers
  • Explore the role that art may have in the development of the reflective practioner

Description:

Over the past several years much has been written about the importance of developing reflective healthcare professionals who are able to provide compassionate, caring, and sustainable healthcare. There is mounting evidence that these traits can be taught in the art gallery. In 2010, The McMaster University Department of Family Medicine and the McMaster Museum of Art introduced the Art of Seeing™, an art-based visual literacy course for Family Medicine Residents. Through facilitated discussions and evidence-based looking, residents interact with each other and selected works of art to improve their individual and collective abilities to find deeper meaning in their professional and personal journeys. The Art of Seeing ™ reflects our responsiveness to Canadian health humanities education and the goals of The Royal College of Physicians and Surgeons of Canada’s CanMEDS Physician Competency Framework.

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Vasiliki Rahimzadeh

Title - Policy relevant truth telling for ethics governance of the data intensive sciences: a tale of two(?) narratives

Objectives:

At the end of the session, the participants will be able to:

  • Appreciate the policy relevant knowledge generated by narrative policy analysis
  • Explore the complementary, competing and overlapping narratives in the ethics of governing data sharing in the data-intensive sciences such as genomics
  • Apply a narrative policy lens to unveil the priorities, politics and problems of contemporary science governance

Description:

This presentation will discuss how narrative policy analysis-and in particular two approaches to narrative policy analysis-can shed light on underlying value conflicts that drive policy processes, politics and problems in genomics and data sharing ethics. Stakeholders in genomics with vested interests in the generation of new scientific knowledge deserve to take part in shaping policies that govern data sharing or, more often than not, restrict it. The collective legacy of the human genome and the promising ability of new sequencing technologies to improve our understanding of human disease substantiate this broader participatory right to engage in science policy processes. The scientific and ethical imperative to share genomic data since sequencing the full human genome accentuates a need for transparency in the motivations and interests being served by data sharing policies. To date, existing methods of bioethics policy research -mostly centered on cost effectiveness, system efficiency and public perceptions studies- do not fully capture the competing values that prevent concerted data sharing among the genomic research community. The complexity, uncertainty and polarization that such value conflicts invite in the face of emerging genomic technologies are at the core of these ethical controversies. They should be embraced, negotiated and reflected in genomics policies, rather than sidelined. This presentation aims to appeal to target audiences with experiences, concerns or interests related to the broader sharing of research data. It furthermore is targeted at stakeholders in public policy making and research.

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Aspasia Karalis

Title - Integrating the medical humanities into competency-based training programs in medical genetics: opportunities and challenges

Objectives:

At the end of the session, the participants will be able to:

  • Summarize the key characteristics of competency-based medical education;
  • Identify potential benefits of integrating the humanities as means of teaching and evaluating the development and acquisition of competencies in professionalism, communication, patient advocacy and leadership;
  • Evaluate the opportunities and challenges for integrating the medical humanities into a competency-based, medical genetics curriculum at their respective academic centres.

Description:

Training in medical genetics across Canada is transitioning towards a « competency-based» education model. This new approach to curriculum design and trainee evaluation is underway in many health profession education programs. With this period of transition comes the opportunity for our community of educators to consider innovative educational strategies for the teaching and evaluation of competency in professionalism, communication skills, patient advocacy and leadership. This presentation will advocate for an increased role for medical humanities in the teaching and evaluation of these core competencies.

 We will first provide a brief overview of what a « competency-based » training curriculum represents for medical genetics training programs. This will be followed by a review of the literature on the role allotted to the medical humanities in various undergraduate and graduate medical education curricula. Evidence suggests that the integration of a medical humanities curriculum into undergraduate and graduate medical education programs may contribute to the development and maintenance of competency in professionalism, communication and empathy, which in turn foster  resilience and well-being for the health professional. From this literature, we will propose an overview of the opportunities and challenges of integrating the medical humanities within the “competency-based” education model for medical genetics.

This session will be of value to trainees and to medical geneticists involved with any aspect of teaching and evaluation of trainees.

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Dr. Alan Peterkin

Title - A Medical Humanities Toolkit-An Interactive Workshop

Objectives:

At the end of the session, the participants will be able to:

  • Appreciate the role of medical humanities in teaching and practice
  • Define narrative competence
  • Define visual literacy
  • Define critical thinking
  • Define reflective capacity
  • Explore the role of reflection in clinician wellbeing

Description:

Over the past several years much has been written about the importance of developing reflective healthcare professionals who are able to provide compassionate, caring, and sustainable healthcare. There is mounting evidence that these traits can be taught in the art gallery. In 2010, The McMaster University Department of Family Medicine and the McMaster Museum of Art introduced the Art of SeeingTM, an art-based visual literacy course for Family Medicine Residents. Through facilitated discussions and evidence-based looking, residents interact with each other and selected works of art to improve their individual and collective abilities to find deeper meaning in their professional and personal journeys. The Art of Seeing TM reflects our responsiveness to Canadian health humanities education and the goals of The Royal College of Physicians and Surgeons of Canada´s CanMEDS Physician Competency Framework.

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Title - Practicing Genetics in the Era of Social Media: An Interactive Workshop

Social media surround us 24/7. Facebook and Twitter, Reddit and YouTube, Wikipedia and the blogosphere. Health professionals and patients alike access social media daily for reasons too numerous to count. This workshop will present some of the uses of social medial in today’s medical practice, and highlight their relevance to patients, healthcare practitioner, and researches.

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