Medicine and Health Sciences Commons^™

A Trial Of Wound Irrigation In The Initial Management Of Open Fracture Wounds, Mohit Bhandari, Kyle J. Jeray, Brad A. Petrisor, P. J. Devereaux, Diane Heels-Ansdell, Emil H. Schemitsch, Jeff Anglen, Gregory J. Della Rocca, Clifford Jones, Hans Kreder, Susan Liew, Paula Mckay, Steven Papp, Parag Sancheti, Sheila Sprague, Trevor B. Stone, Xin Sun, Stephanie L. Tanner, Paul Tornetta, Ted Tufescu, Stephen Walter, Gordon H. Guyatt

Bone and Joint Institute

Copyright © 2015 Massachusetts Medical Society. BACKGROUND The management of open fractures requires wound irrigation and dridement to remove contaminants, but the effectiveness of various pressures and solutions for irrigation remains controversial. We investigated the effects of castile soap versus normal saline irrigation delivered by means of high, low, or very low irrigation pressure. METHODS In this study with a 2-by-3 factorial design, conducted at 41 clinical centers, we randomly assigned patients who had an open fracture of an extremity to undergo irrigation with one of three irrigation pressures (high pressure [>20 psi], low pressure [5 to 10 psi], …

The Rho Gtpases Rac1, Cdc42, And Rhoa Regulate App Transport To Lysosomes And Aβ Production, Justin K. Chiu .

Electronic Thesis and Dissertation Repository

Alzheimer’s Disease (AD) is characterized by Beta-Amyloid (Aβ) plaques within the brain. Aβ peptides are produced by the cleavage of Amyloid Precursor Protein (APP). Our lab has previously discovered a novel pathway for APP internalization mediated by ADP-ribosylation factor 6 (Arf6). This pathway resembles macropinocytosis, transporting cell surface APP directly to lysosomes, a possible site for Aβ production. We set out to characterize the effectors downstream of Arf6. In SN56 and N2A cells we co-transfected HA-tagged APP (to label cell-surface APP) with compartment markers, to visualize APP trafficking. We used dominant negative and constitutively active mutants, pharmacological inhibitors, and siRNA …

Phase Ii Clinical Trial Of Concurrent Neoadjuvant Chemotherapy With Radiotherapy In Locally Advanced Breast Cancer, Muriel Brackstone

Electronic Thesis and Dissertation Repository

Locally advanced breast cancer (LABC) represents 15% of all non-metastatic breast cancers, with an overall poor prognosis, despite current guidelines that recommend neoadjuvant chemotherapy followed by surgery and adjuvant radiation. Therefore, a novel treatment paradigm using concurrent neoadjuvant chemoradiotherapy was proposed. A clinical trial was designed, where 32 LABC patients were treated with q3 weekly 5-fluorouracil, epirubicin and cyclophosphamide for three cycles, followed by weekly docetaxel for 9 weeks with concurrent regional radiation (45+5.4Gy) for the first 6 weeks. Patients subsequently underwent modified radical mastectomies. Pathological complete responses (pCR) and 3 year overall survival rates were compared to a matched …

Evidence Reversal: When New Evidence Contradicts Established Practices, Desiree S. Sutton

Electronic Thesis and Dissertation Repository

Evidence reversal occurs when new evidence contradicts established practices. The first component of this thesis is an umbrella overview of investigations – reviews and collections of studies – into evidence reversal to gather concepts and methods that we identified as useful to lay a foundation for a standardized ‘theory of reversal.’ The foundation of this review enables the construction of a framework that will provide structure to this field, as no formal organization currently exists. The next component builds upon this foundation and proposes a framework for evidence reversal and its related concepts. The second review takes this framework …

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Quality Of Life And Subjective Outcomes Following Maxillomandibular Advancement Surgery For The Treatment Of Obstructive Sleep Apnea, Andrew D. Emanuele

Electronic Thesis and Dissertation Repository

Objective: The aim of this study was to assess outcomes related to general quality of life, daytime sleepiness and functional sleep outcomes, functional outcomes of orthognathic surgery, and facial aesthetics in patients undergoing maxillomandibular advancement (MMA) surgery for the treatment of obstructive sleep apnea (OSA).

Materials and Methods: This was a cross-sectional self-report study. A questionnaire was constructed using questions drawn from previously validated questionnaires. The survey was distributed to 25 patients who underwent MMA surgery for the treatment of OSA at LHSC in London, Ontario by a single surgeon between 2002 and 2013.

Results: The survey results showed that …

The Role Of Bone Sialoprotein In Periodontal Tissue Development And Bone Repair, Yohannes Soenjaya

Electronic Thesis and Dissertation Repository

Bone development and repair involve complex processes that include interaction between cells and their surrounding matrix. In the body, bone sialoprotein (BSP) expression is up-regulated at the onset of mineralization. BSP is a multifunctional acidic phosphoprotein with collagen-binding, hydroxyapatite nucleating, and integrin recognition (RGD sequence, which is important for cell-attachment and signaling) regions. Mice lacking BSP expression (Bsp^-/-), exhibit a bone phenotype with reductions in bone mineral density, bone length, osteoclast activation, and impaired bone healing. This thesis examined the role of BSP in tooth development and also its potential use as a therapeutic reagent for bone …

Exercise Identity: Origins, Applications, And Future Utility, Vincent L. Liardi

Electronic Thesis and Dissertation Repository

It has been determined that exercise identity (EI) is a key component of the self-concept and is a strong determinant of exercise behaviours. The primary purpose of study 1 was to examine EI’s relationship with three key self-presentational variables: self-presentational efficacy (SPE), social physique anxiety (SPA), and impression motivation (IM). Specifically, we looked at how EI contributed uniquely to predicting exercise behaviour over and above these self-presentational concerns. The analyses demonstrated that EI is positively correlated with SPE and unrelated to SPA in both genders. Further analyses revealed that EI contributes a significant amount of variance towards exercise behaviour over …

Semantic Integration In Adults With Nonverbal Learning Disabilities And Autism Spectrum Disorder: Influence Of Word Knowledge And Gestalt Perception, Margot E. Stothers

Electronic Thesis and Dissertation Repository

Language in individuals with nonverbal learning disabilities (NLD) and autism spectrum disorder (ASD) has been described as semantically empty and impoverished, despite apparently average word knowledge. Here, inter-related studies explored semantic representations in adults with these disorders of social perception. Studies highlighted semantic integration, a form of gestalt perception in which new concepts are developed by connecting familiar terms in novel ways. Semantic integration was compared to vocabulary breadth, and to nonverbal gestalt perception, comparing clinical groups to each other and to adults without a diagnosis. Because weaknesses in gestalt perception have been seen in NLD and ASD, it was …

Intracellular Acidification In Brain Tumors Induced By Topiramate : In-Vivo Detection Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Kamini Y. Marathe

Electronic Thesis and Dissertation Repository

Glioblastoma Multiforme (GBM) is the most aggressive and malignant form of primary brain tumor. In many tumors, increased intracellular pH (pH_i) is a hallmark of aggressiveness. This increased pH_i has been shown to be related to cell proliferation and evasion of apoptosis as well as resistance to chemotherapy. As such, monitoring pH_i and the tumor pH_i response to pharmacologic challenge, may aid in treatment planning and patient management for this deadly cancer. A magnetic resonance imaging (MRI) method called Chemical Exchange Saturation Transfer (CEST) has been used to detect changes in pH_i. Our group …

Smoking And Exercise: Mechanisms And Effects During Simulated And Genuine Quit Attempts, Stefanie De Jesus

Electronic Thesis and Dissertation Repository

Cigarette smoking is a leading agent for premature morbidity and mortality among the global community. Most individuals surrender to tobacco use disorder due to the inability to cope with cravings and withdrawal symptoms. Exercise appears to provide acute relief. Currently, it is unclear how exercise attenuates these reductions. Furthermore, the available evidence has focused on acute outcomes besides smoking behaviour and is limited to simulated quit attempts. Three experimental studies were designed to address these outstanding issues. Not surprisingly, a bout of moderate intensity exercise was found in study 1 (chapter 2) to reduce cravings associated with a temporary period …

Mothers Experiencing Homelessness: Social Exclusion, Resistance, And Health, Sarah Benbow

Electronic Thesis and Dissertation Repository

Background and Purpose: Mothers experiencing homelessness in Canada are faced with unique challenges in achieving health. The purpose of this two-phase study was to critically examine the socio-political context, health needs, exclusionary and inclusionary forces, and strategies of resistance demonstrated by mothers experiencing homelessness.

Methodology: This study falls under the critical paradigm informed by the theoretical perspective of intersectionality. Methodologies employed included critical narrative and critical discourse analysis. Data were collected at various homeless shelters and programs that provide services for women and mothers who are homeless in Southern Ontario. A purposive sample of women experiencing homelessness, and service …

Towards The Development Of A Wearable Tremor Suppression Glove, Yue Zhou

Electronic Thesis and Dissertation Repository

Patients diagnosed with Parkinson’s disease (PD) often associate with tremor. Among other symptoms of PD, tremor is the most aggressive symptom and it is difficult to control with traditional treatments. This thesis presents the assessment of Parkinsonian hand tremor in both the time domain and the frequency domain, the performance of a tremor estimator using different tremor models, and the development of a novel mechatronic transmission system for a wearable tremor suppression device. This transmission system functions as a mechatronic splitter that allows a single power source to support multiple independent applications. Unique features of this transmission system include low …

The Use Of Exercise Self-Talk By Female Adolescents, Sadie Puddister

Electronic Thesis and Dissertation Repository

Already below recommended levels, physical activity participation in female youth is known to decline throughout adolescence. Self-talk, a form of self-regulation has been demonstrated to influence behaviour in both sport and exercise settings. The purpose of the present research was to explore the exercise related self-talk of teen girls (aged 14-18) with the intent of uncovering reoccurring themes and attributes in the self-talk of both low frequency exercisers (LFEs) and high frequency exercisers (HFEs). Participants were teen girls (N=28, M_age=15.56, SD_age=1.47) recruited from A. B. Lucas Secondary School in London, Ontario. Physical activity …

Evidence For Using Immunosuppressive Treatments When Treating Idiopathic Non-Infectious Uveitis: A Systematic Review And Meta-Analysis, Hargurinder Singh

Electronic Thesis and Dissertation Repository

Idiopathic non-infectious uveitis is the spontaneous inflammation of the eye, which can lead to blindness if not treated correctly. Due to long-term side effects of corticosteroids, 4 classes of off-label immunosuppressive treatments are sometimes used (alkylating agents, inhibitors of T-lymphocyte signalling, antimetabolites and biological modifiers). We conducted a systematic review and meta-analysis to assess the effectiveness of different treatment classes on uveitis patients with similar characteristics. Results of the systematic review concurred with the conclusions from the meta-analysis, which found that all immunosuppressive treatments improved patient vision, with a statistically significant change in logMAR of -0.11 (95% CI of -0.152 …

Overcoming Innate And Acquired Therapy Resistance By Targeting Dna Repair In Human Cancer Cells, Mateusz Rytelewski

Electronic Thesis and Dissertation Repository

Genomic instability and a high mutation rate lead to heterogeneity in human tumors. Mathematical modelling predicts that these characteristics promote acquired resistance to cytotoxic and targeted therapies, by increasing the likelihood that resistant subpopulations exist at the start of treatment (and promoting the accumulation of de novo resistance mutations during treatment). As a result, genome plasticity promotes increased fitness on the population level, but individual tumor cells must nonetheless maintain a level of DNA integrity that allows for continued survival, particularly in the context of DNA-damaging therapy (which DNA repair counteracts). Thus, DNA repair proteins are a source of innate …

Physical Exertion As A Risk Factor For Ventricular Arrhythmia: A Prospective Cohort Study, Harpreet S. Chahal

Electronic Thesis and Dissertation Repository

Episodes of physical exertion are associated with an immediately higher risk of cardiovascular events while physical activity over the long-term is cardioprotective. To assess the transient and long-term risk of ventricular arrhythmia (VA), we conducted a nested case-crossover study within a prospective cohort of 97 patients with implantable cardioverter-defibrillators (ICD). Within an hour of episodes of exertion, the risk of VA was 5.3 (95% CI 2.7 – 10.6) times greater compared to periods of rest. The association was higher among patients with aerobic fitness below the median (RR[relative risk]=17.5, 95% 5.2 – 58.5) than for patients with aerobic fitness above …

Intracellular Trafficking Governs The Processing Of The Amyloid Precursor Protein And The Secretion Of Beta-Amyloid, Joshua Hoi Ki Tam

Electronic Thesis and Dissertation Repository

One of the hallmarks of Alzheimer’s disease (AD) is the pathological accumulation of β-amyloid (Aβ) in the brains of AD patients. Oligomeric and fibrillar aggregates of Aβ have been shown to be neurotoxic to neurons and hippocampal slices. Therefore, limiting Aβ production is an important area of research in order to delay or stop AD progression. Aβ is produced by amyloidogenic cleavage of amyloid precursor protein (APP). Amyloidogenic cleavage requires ectodomain removal by β-secretase and intramembrane γ-cleavage by γ-secretase to release Aβ products ranging from 38-43 residues. Work from our lab has shown that APP and γ-secretase are resident proteins …

Complications Of Vaginal Synthetic Sling Surgeries In Women: Population Based Cohort Study, Hanaa Al-Hothi

Electronic Thesis and Dissertation Repository

Synthetic sling surgery is the procedure of choice for surgical correction of stress urinary incontinence (SUI) in females. However, complications are recognized, with surgical intervention to treat them in some instances. In a retrospective study we identified and analyzed those complication to determine their incidence and associated predictive factors. A total of 59,887 women who had synthetic sling procedure were included. Incidence of surgically treated complications was 2.2 % ((95% CI 2.07- 2.30) and on 10 years follow up cumulative incident rate was 3.3% (95% CI 3.0- 3.5). There was no significant difference in complication rate between urologists versus gynecologists. …

Pathophysiologic Mechanisms Of Immune-Mediated Drug Hypersensitivity Reactions To Sulfonamides, Elham A. Sultan

Electronic Thesis and Dissertation Repository

As sulfonamide hypersensitivity reactions are serious clinical problem, it is necessary to determine which patients tolerate therapy and which patients are at risk. Although the exact pathogenesis of these reactions remains unclear, the imbalance in the production and detoxification of reactive sulfamethoxazole (SMX) metabolites appears to be important in the propagation of these reactions. It is known that these reactive metabolites can cause lymphocytes toxicity and produce reactive oxygen species (ROS) which can damage proteins, lipids, and DNA. The hypothesis of this research is that there are differences in cytotoxicity and expression of oxidative stress to reactive SMX metabolites in …

"A Family Doctor Can Do That!" Is There A Role For A Formalized Referral Network For Office Procedures In Family Practices Of Newfoundland And Labrador?, Annabeth J. Loveys

Electronic Thesis and Dissertation Repository

Office procedures are an important part of the comprehensive care package provided by family physicians. Every family physician cannot feasibly perform every office procedure. A cadre of family physicians drawing upon each other’s procedural skills has the potential to improve patient care and enhance physician satisfaction. A mixed methods approach was used to explore potential clinical and educational roles of a formalized referral networkfor office procedures in Newfoundland and Labrador, Canada. In a quantitative study, using a self-administered survey, family physicians identified that while there are procedures being performed in family practice, there is a discrepancy between the demand for, …

Greater Magnocellular Saccadic Suppression In High Versus Low Autistic Tendency Suggests A Causal Path To Local Perceptual Style., David P Crewther, Daniel Crewther, Stephanie Bevan, Melvyn A Goodale, Sheila G Crewther

Brain and Mind Institute Researchers' Publications

Saccadic suppression-the reduction of visual sensitivity during rapid eye movements-has previously been proposed to reflect a specific suppression of the magnocellular visual system, with the initial neural site of that suppression at or prior to afferent visual information reaching striate cortex. Dysfunction in the magnocellular visual pathway has also been associated with perceptual and physiological anomalies in individuals with autism spectrum disorder or high autistic tendency, leading us to question whether saccadic suppression is altered in the broader autism phenotype. Here we show that individuals with high autistic tendency show greater saccadic suppression of low versus high spatial frequency gratings …

Trends In Psychotropic Dispensing Among Older Adults With Dementia Living In Long-Term Care Facilities: 2004-2013., Akshya Vasudev, Salimah Z Shariff, Kuan Liu, Amer M Burhan, Nathan Herrmann, Sean Leonard, Muhammad Mamdani

Psychiatry Publications

OBJECTIVE: Guidelines worldwide have cautioned against the use of antipsychotics as first-line agents to treat neuropsychiatric symptoms of dementia. We aimed to investigate the changes over time in the dispensing of antipsychotics and other psychotropics among older adults with dementia living in long-term care facilities.

METHODS: We used drug claims data from Ontario, Canada, to calculate quarterly rates of prescription dispensing of six psychotropic drug classes among all elderly (≥65 years of age) long-term care residents with dementia from January 1, 2004, to March 31, 2013. Psychotropic drugs were classified into the following categories: atypical and conventional antipsychotics, non-sedative and …

An Intra-Bone Axial Load Transducer: Development And Validation In An In-Vitro Radius Model, Nikolas K. Knowles, Michael Gladwell, Louis M. Ferreira

Surgery Publications

Background

Accurate measurement of forces through the proximal radius can assess the effects of some surgical procedures on radioulnar load sharing, but is difficult to achieve given the redundant loading nature of the musculoskeletal system. Previously reported devices have relied on indirect measurements that may alter articular joint location and function. An axial load transducer interposed in the diaphysis of the radius may accurately quantify unknown axial loads of the proximal radius, and maintain articular location.

Methods

An in-vitro radius model was developed by interposing an axial load transducer in the diaphysis of the proximal radius. Static loads of 20, …

Declining Incidence Of Stroke And Dementia: Coincidence Or Prevention Opportunity?, Luciano A. Sposato, Moira K. Kapral, Jiming Fang, Sudeep S. Gill, Daniel G. Hackam, Lauren E. Cipriano, Vladimir Hachinski

Anatomy and Cell Biology Publications

No abstract provided.

Estimating Osteoporotic Fracture Risk Following A Wrist Fracture: A Tale Of Two Systems, Karen Beattie, Jonathan Adachi, George Ioannidis, Alexandra Papaioannou, William D. Leslie, Ruby Grewal, Joy Macdermid, Anthony B. Hodsman

Bone and Joint Institute

© 2015, The Author(s). Summary: The WHO fracture risk assessment (FRAX) and Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools can both be used to determine an individual’s 10-year risk of osteoporotic fracture. However, these tools differ in their risk calculation. For participants fracture, FRAX provides a lower fracture risk estimate than CAROC resulting in fewer decisions to initiate therapy.Purpose: The purpose of the current report is to compare fracture risk prediction rates using the CAROC and the FRAX® tools.Methods: Individuals ≥50 years with a distal radius fracture resulting from a fall from standing height or less were recruited …

Functional Outcomes Of Acutely Infected Knee Arthroplasty: A Comparison Of Different Surgical Treatment Options, Ivan Dzaja, James Howard, Lyndsay Somerville, Brent Lanting

Bone and Joint Institute

© 2015 8872147 Canada Inc. Background: An infected total knee arthroplasty (TKA) can be treated with irrigation and débridement with polyethylene exchange (IDPE) or a 2-staged revision (2SR). Although research has examined infection eradication rates of both treatments, patient outcomes have not been reported. We examined patient-reported outcomes following treatment compared with matched, noninfected controls. Methods: We retrospectively identified patients with infected TKAs who had undergone the index procedure between May 1991 and November 2011. Patient-reported outcomes included the 12-item Short Form Health Survey, Western Ontario and McMaster Universities Arthritis Index, and Knee Society Scores as well as range of …

The Child And Adolescent Scale Of Environment (Case): Further Validation With Youth Who Have Chronic Conditions, Gary Bedell, Janette Mcdougal

Occupational Therapy Publications

Objective: To further validate the Child and Adolescent Scale of Environment (CASE).

Methods: Baseline data (n = 430) were analyzed from a longitudinal study on quality of life for youth with chronic conditions ages 11–17 in Ontario, Canada. Internal consistency and structure, and convergent and discriminant validity were examined via Cronbach’s alpha (α), exploratory factor analyses, correlation analyses and ANOVA.

Results: The CASE had high internal consistency (α = 0.89). A three-factor solution was produced with 55% variance explained: (1) Community/Home Resources, (2) School Resources and (3) Physical Design/Access). CASE total and factor …

Methods And Considerations For The Analysis And Standardization Of Assessing Muscle Sympathetic Nerve Activity In Humans, Daniel W. White, J. Kevin Shoemaker, Peter B. Raven

Bone and Joint Institute

© 2015 Elsevier B.V.. The technique of microneurography and the assessment of muscle sympathetic nerve activity (MSNA) are used in laboratories throughout the world. The variables used to describe MSNA, and the criteria by which these variables are quantified from the integrated neurogram, vary among studies and laboratories and, therefore, can become confusing to those starting to learn the technique. Therefore, the purpose of this educational review is to discuss guidelines and standards for the assessment of sympathetic nervous activity through the collection and analysis of MSNA. This review will reiterate common practices in the collection of MSNA, but will …

Factors Impacting Transgender Patients’ Discomfort With Their Family Physicians: A Respondent-Driven Sampling Survey, Greta R. Bauer, Xuchen Zong, Ayden I. Scheim, Rebecca Hammond, Amardeep Thind

Epidemiology and Biostatistics Publications

BACKGROUND: Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada.

METHODS: 433 trans people age 16 and over were surveyed using respondent-driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via …