Ottawa Hospital Research Institute

Bells Corners, Canada

Ottawa Hospital Research Institute

Bells Corners, Canada

The Ottawa Hospital Research Institute , formerly Ottawa Health Research Institute, is a non-profit academic health research institute located in the city of Ottawa. It was formed in 2001 following the merger of three Ottawa hospitals. The Ottawa Hospital Research Institute is the research arm of The Ottawa Hospital and affiliated with the University of Ottawa.As of April 2013, the Ottawa Hospital Research Institute houses approximately 560 scientists and clinical investigators, 475 students and research fellows, and 700 support staff. It has five research programs: Cancer Therapeutics; Chronic Disease; Clinical Epidemiology; Regenerative Medicine; and Neuroscience.Ronald G. Worton was the research institute's founding CEO and Scientific Director in 2001. In 2007, Duncan Stewart, formerly Chief Cardiologist of St. Michael's Hospital in Toronto and Director of Cardiology of University of Toronto, took over as CEO and Scientific Director. Wikipedia.

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Ottawa Hospital Research Institute | Date: 2016-11-30

A method for identifying bleeding in a patient, comprising: receiving a four-dimensional data set comprising vascular voxels, each of the voxels representing a three-dimensional location of a time-varying signal; identifying the vascular voxels in the data set by comparing each time-varying signal of each voxel in the data set to a variance threshold; identifying, within the vascular voxels in the data set, blood vessel site voxels by comparing each time-varying signal of the vascular voxels to a model arterial and venous signals; generating clusters of voxels in the data set; separating the clusters of voxels into a subset of blood vessel site clusters and a subset of remaining clusters; identifying, within the subset of remaining clusters, one or more clusters that are spatially growing over time to determine one or more active bleed sites in the patient; and generating an alert if one or more active bleed sites are determined.

Ottawa Hospital Research Institute | Date: 2016-08-19

There are provided compositions and methods for modulating stem cell division decisions, in particular, division symmetry. It has been demonstrated that wnt7a acts through frizzled-7 receptor expressed on the surface of adult stem cells, e.g. satellite stem cells, to activate the planar cell polarity (PCP) pathway, thereby promoting symmetrical expansion of stem cells. The compositions and methods of the invention are useful, for example, in modulating stem cell division symmetry in vitro and in vivo, in replenishing and expanding the stem cell pool, and in promoting the formation, maintenance, repair and regeneration of tissue.

Ottawa Hospital Research Institute | Date: 2015-03-27

The invention provides cell therapy compositions and associated methods. In particular embodiments, improved therapeutic cells and improved cell-based gene therapies for promoting cell or tissue formation, regeneration, repair or maintenance in a subject in need thereof are provided.

A system and method are provided that employ the variability of physiological waveforms to estimate the time to death after WLST, or time to inadequate organ perfusion. From the variability data one can derive an index subsequently used to determine the probability of death (or inadequate organ perfusion) within a given time frame in an automated fashion from bedside monitors in the intensive or post-anesthesia care unit. The resulting variability index can also be combined with the clinical variables used in other death prediction tools to enhance the performance and outcome when compared to existing models. In at least one implementation, variability monitoring at the bedside could be used to provide estimates of the probability that a patient will die within a certain time frame after WLST. These estimates could be used to reduce the distress of the patients families, as well as optimize the use of resources surrounding donation.

Bassett E.A.,Ottawa Hospital Research Institute | Wallace V.A.,Ottawa Hospital Research Institute | Wallace V.A.,University of Ottawa
Trends in Neurosciences | Year: 2012

The vertebrate retina is a well-characterized and tractable model for studying neurogenesis. Retinal neurons and glia are generated in a conserved sequence from a pool of multipotent progenitor cells, and numerous cell fate determinants for the different classes of retinal cell types have been identified. Here, we summarize several recent developments in the field that have advanced understanding of the regulation of multipotentiality and temporal competence of progenitors. We also discuss recent insights into the relative influence of lineage-based versus stochastic modes of cell fate determination. Enhancing and integrating knowledge of the molecular and genetic machinery underlying retinal development is critically important for understanding not only normal developmental mechanisms, but also therapeutic interventions aimed at restoring vision loss. © 2012.

Wells P.,Ottawa Hospital Research Institute
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

Venous thromboembolism (VTE) is a common condition that can lead to complications such as postphlebitic syndrome, chronic pulmonary artery hypertension, and death. The approach to the diagnosis of has evolved over the years and an algorithm strategy combining pretest probability, D-dimer testing, and diagnostic imaging now allows for safe, convenient, and cost-effective investigation of patients. Patients with low pretest probability and a negative D-dimer can have VTE excluded without the need for imaging. The mainstay of treatment of VTE is anticoagulation, whereas interventions such as thrombolysis and inferior vena cava filters are reserved for special situations. Low-molecular-weight heparin has allowed for outpatient management of most patients with deep vein thrombosis at a considerable cost savings to the health care system. Patients with malignancy-associated VTE benefit from decreased recurrent rates if treated with long-term low-molecular-weight heparin. The development of new oral anticoagulants further simplifies treatment. The duration of anticoagulation is primarily influenced by underlying cause of the VTE (whether provoked or not) and consideration of the risk for major hemorrhage. Testing for genetic and acquired thrombophilia may provide insight as to the cause of a first idiopathic deep vein thrombosis, but the evidence linking most thrombophilias to an increased risk of recurrent thrombosis is limited.

Yin H.,Ottawa Hospital Research Institute | Price F.,Ottawa Hospital Research Institute | Rudnicki M.A.,Ottawa Hospital Research Institute
Physiological Reviews | Year: 2013

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. © 2013 the American Physiological Society.

Turner L.,Ottawa Hospital Research Institute
Cochrane database of systematic reviews (Online) | Year: 2012

An overwhelming body of evidence stating that the completeness of reporting of randomised controlled trials (RCTs) is not optimal has accrued over time. In the mid-1990s, in response to these concerns, an international group of clinical trialists, statisticians, epidemiologists, and biomedical journal editors developed the CONsolidated Standards Of Reporting Trials (CONSORT) Statement. The CONSORT Statement, most recently updated in March 2010, is an evidence-based minimum set of recommendations including a checklist and flow diagram for reporting RCTs and is intended to facilitate the complete and transparent reporting of trials and aid their critical appraisal and interpretation. In 2006, a systematic review of eight studies evaluating the "effectiveness of CONSORT in improving reporting quality in journals" was published. To update the earlier systematic review assessing whether journal endorsement of the 1996 and 2001 CONSORT checklists influences the completeness of reporting of RCTs published in medical journals. We conducted electronic searches, known item searching, and reference list scans to identify reports of evaluations assessing the completeness of reporting of RCTs. The electronic search strategy was developed in MEDLINE and tailored to EMBASE. We searched the Cochrane Methodology Register and the Cochrane Database of Systematic Reviews using the Wiley interface. We searched the Science Citation Index, Social Science Citation Index, and Arts and Humanities Citation Index through the ISI Web of Knowledge interface. We conducted all searches to identify reports published between January 2005 and March 2010, inclusive. In addition to studies identified in the original systematic review on this topic, comparative studies evaluating the completeness of reporting of RCTs in any of the following comparison groups were eligible for inclusion in this review: 1) Completeness of reporting of RCTs published in journals that have and have not endorsed the CONSORT Statement; 2) Completeness of reporting of RCTs published in CONSORT-endorsing journals before and after endorsement; or 3) Completeness of reporting of RCTs before and after the publication of the CONSORT Statement (1996 or 2001). We used a broad definition of CONSORT endorsement that includes any of the following: (a) requirement or recommendation in journal's 'Instructions to Authors' to follow CONSORT guidelines; (b) journal editorial statement endorsing the CONSORT Statement; or (c) editorial requirement for authors to submit a CONSORT checklist and/or flow diagram with their manuscript. We contacted authors of evaluations reporting data that could be included in any comparison group(s), but not presented as such in the published report and asked them to provide additional data in order to determine eligibility of their evaluation. Evaluations were not excluded due to language of publication or validity assessment. We completed screening and data extraction using standardised electronic forms, where conflicts, reasons for exclusion, and level of agreement were all automatically and centrally managed in web-based management software, DistillerSR(®). One of two authors extracted general characteristics of included evaluations and all data were verified by a second author. Data describing completeness of reporting were extracted by one author using a pre-specified form; a 10% random sample of evaluations was verified by a second author. Any discrepancies were discussed by both authors; we made no modifications to the extracted data. Validity assessments of included evaluations were conducted by one author and independently verified by one of three authors. We resolved all conflicts by consensus.For each comparison we collected data on 27 outcomes: 22 items of the CONSORT 2001 checklist, plus four items relating to the reporting of blinding, and one item of aggregate CONSORT scores. Where reported, we extracted and qualitatively synthesised data on the methodological quality of RCTs, by scale or score. Fifty-three publications reporting 50 evaluations were included. The total number of RCTs assessed within evaluations was 16,604 (median per evaluation 123 (interquartile range (IQR) 77 to 226) published in a median of six (IQR 3 to 26) journals. Characteristics of the included RCT populations were variable, resulting in heterogeneity between included evaluations. Validity assessments of included studies resulted in largely unclear judgements. The included evaluations are not RCTs and less than 8% (4/53) of the evaluations reported adjusting for potential confounding factors.   Twenty-five of 27 outcomes assessing completeness of reporting in RCTs appeared to favour CONSORT-endorsing journals over non-endorsers, of which five were statistically significant.

Bennett C.,Ottawa Hospital Research Institute
PLoS medicine | Year: 2010

Research needs to be reported transparently so readers can critically assess the strengths and weaknesses of the design, conduct, and analysis of studies. Reporting guidelines have been developed to inform reporting for a variety of study designs. The objective of this study was to identify whether there is a need to develop a reporting guideline for survey research. We conducted a three-part project: (1) a systematic review of the literature (including "Instructions to Authors" from the top five journals of 33 medical specialties and top 15 general and internal medicine journals) to identify guidance for reporting survey research; (2) a systematic review of evidence on the quality of reporting of surveys; and (3) a review of reporting of key quality criteria for survey research in 117 recently published reports of self-administered surveys. Fewer than 7% of medical journals (n = 165) provided guidance to authors on survey research despite a majority having published survey-based studies in recent years. We identified four published checklists for conducting or reporting survey research, none of which were validated. We identified eight previous reviews of survey reporting quality, which focused on issues of non-response and accessibility of questionnaires. Our own review of 117 published survey studies revealed that many items were poorly reported: few studies provided the survey or core questions (35%), reported the validity or reliability of the instrument (19%), defined the response rate (25%), discussed the representativeness of the sample (11%), or identified how missing data were handled (11%). There is limited guidance and no consensus regarding the optimal reporting of survey research. The majority of key reporting criteria are poorly reported in peer-reviewed survey research articles. Our findings highlight the need for clear and consistent reporting guidelines specific to survey research.

Albert P.R.,Ottawa Hospital Research Institute
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

The serotonin-1A (5-HT1A) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT1A receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT1A receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT1A receptor gene (Htr1a). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT1A autoreceptor expression in animal models and humans. Its association with altered 5-HT1A expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene × environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT1A heteroreceptors, and rs6295-induced upregulation of 5-HT1A autoreceptors. Targeted therapeutics to inhibit 5-HT1A autoreceptor expression and induce 5-HT1A heteroreceptor expression may ameliorate treatment of anxiety and major depression. © 2012 The Royal Society.

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