Knowledge Mobilization Leads to Social Innovation

Building the capacity for KMb will benefit universities and communities. Through knowledge brokers, resources, and clear language research summaries, the KMb Unit at York is working to maximize the social, cultural, and economic impact of research.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

The Promise of Johannesburg: Fisheries and the World Summit on Sustainable Development

This article briefly examines the world fish crisis and the factors that drive overuse of ocean resources. It identifies some of the major trends in ocean fishing that have led to over-exploitation and briefly reviews the weaknesses of international fishery arrangements that led to WSSD. It describes and evaluates the outcomes of the WSSD and suggests some measures that can and must be taken to the address the crisis facing world ocean fish stocks

A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status Epilepticus in a Resource-Limited Setting

Introduction: Pediatric convulsive status epilepticus (CSE) which is refractory to first-line benzodiazepines is a significant clinical challenge, especially within resource-limited countries. Parenteral phenobarbital is widely used in Africa as second-line agent for pediatric CSE, however evidence to support its use is limited.Purpose: This study aimed to compare the use of parenteral phenobarbital against parenteral phenytoin as a second-line agent in the management of pediatric CSE.Methodology: An open-labeled single-center randomized parallel clinical trial was undertaken which included all children (between ages of 1 month and 15 years) who presented with CSE. Children were allocated to receive either parenteral phenobarbital or parenteral phenytoin if they did not respond to first-line benzodiazepines. An intention-to-treat analysis was performed with the investigators blinded to the treatment arms. The primary outcome measure was the success of terminating CSE. Secondary outcomes included the need for admission to the pediatric intensive care unit (PICU) and breakthrough seizures during the admission. In addition, local epidemiological data was collected on the burden of pediatric CSE.Results: Between 2015 and 2018, 193 episodes of CSE from 111 children were enrolled in the study of which 144 met the study requirements. Forty-two percent had a prior history of epilepsy mostly from structural brain pathology (53%). The most common presentation was generalized CSE (65%) caused by acute injuries or infections of the central nervous system (59%), with 19% of children having febrile status epilepticus. Thirty-five percent of children required second-line management. More patients who received parenteral phenobarbital were at a significantly reduced risk of failing second-line treatment compared to those who received parenteral phenytoin (RR = 0.3, p = 0.0003). Phenobarbital also terminated refractory CSE faster (p < 0.0001). Furthermore, patients who received parenteral phenobarbital were less likely to need admission to the PICU. There was no difference between the two groups in the number of breakthrough seizures that occurred during admission.Conclusion: Overall this study supports anecdotal evidence that phenobarbital is a safe and effective second-line treatment for the management of pediatric CSE. These results advocate for parenteral phenobarbital to remain available to health care providers managing pediatric CSE in resource-limited settings.Attachments: CONSORT 2010 checklistTrial registration: NCT03650270Full trial protocol available:https://clinicaltrials.gov/ct2/show/NCT03650270?recrs=e&type=Intr&cond=Status+Epilepticus&age=0&rank=

Trials of large group teaching in Malaysian private universities: a cross sectional study of teaching medicine and other disciplines

<p>Abstract</p> <p>Background</p> <p>This is a pilot cross sectional study using both quantitative and qualitative approach towards tutors teaching large classes in private universities in the Klang Valley (comprising Kuala Lumpur, its suburbs, adjoining towns in the State of Selangor) and the State of Negeri Sembilan, Malaysia. The general aim of this study is to determine the difficulties faced by tutors when teaching large group of students and to outline appropriate recommendations in overcoming them.</p> <p>Findings</p> <p>Thirty-two academics from six private universities from different faculties such as Medical Sciences, Business, Information Technology, and Engineering disciplines participated in this study. SPSS software was used to analyse the data. The results in general indicate that the conventional instructor-student approach has its shortcoming and requires changes. Interestingly, tutors from Medicine and IT less often faced difficulties and had positive experience in teaching large group of students.</p> <p>Conclusion</p> <p>However several suggestions were proposed to overcome these difficulties ranging from breaking into smaller classes, adopting innovative teaching, use of interactive learning methods incorporating interactive assessment and creative technology which enhanced students learning. Furthermore the study provides insights on the trials of large group teaching which are clearly identified to help tutors realise its impact on teaching. The suggestions to overcome these difficulties and to maximize student learning can serve as a guideline for tutors who face these challenges.</p

The Promise of Johannesburg: Fisheries and the World Summit on Sustainable Development

This article briefly examines the world fish crisis and the factors that drive overuse of ocean resources. It identifies some of the major trends in ocean fishing that have led to over-exploitation and briefly reviews the weaknesses of international fishery arrangements that led to WSSD. It describes and evaluates the outcomes of the WSSD and suggests some measures that can and must be taken to the address the crisis facing world ocean fish stocks

Knowledge mobilisation builds local research collaborations for social innovation

Knowledge mobilisationUniversities seek to maximise the impact of their research by investing in technology commercialisation services but universities fail to support the various impacts of non-commercial research. This paper describes the experience of York University (Toronto, Canada) in developing the institutional capacity to support knowledge mobilisation to maximise the impacts of research from the social sciences and humanities. York works in partnership with local research users to provide enhanced access to research through dedicated support for research collaborations. Grounded in theories of knowledge transfer and exchange, and illustrated with examples, this paper demonstrates how investments in knowledge mobilisation create value for the institution, researchers, graduate students and research partners

Studies of the MYM-type zinc finger protein ZMYM3

RNase H2 is a trimeric ribonuclease that specifically degrades the RNA moiety of DNARNA hybrids. Mutations in RNase H2 result in Aicardi–Goutières syndrome (AGS), a rare inflammatory disorder notable for being a ‘mendelian mimic’ of congenital viral brain infection. Some AGS-associated mutations in the RNase H2B subunit do not affect the catalytic activity of the RNase H2 *in vitro* and are clustered together on the surface of the complex, suggesting a possible role for these residues in mediating important interactions of RNase H2. I set out to identify binding partner(s) of RNase H2B whose binding is impaired by this cluster of mutations, by screening for interactors of FLAG-tagged wild-type and mutant RNase H2B in HEK293T cells. In this work, I identify several members of a putative chromatin-silencing complex as novel RNase H2B binding partners whose binding is impaired by each mutation in this cluster, including: HDAC2, a histone deacetylase, LSD1, a histone demethylase, CoREST, a co-repressor of transcription, TFII-I, a transcription factor, and ZMYM3, an MYM-type zinc finger protein of unknown function. By making several truncation mutants of ZMYM3, I show that a C-terminal region containing a ‘PXP’ repeat motif mediates its interaction with RNase H2, and that the PXP-containing proteins ZMYM2 and ZMYM4 interact with RNase H2, whereas the PXP-null proteins ZMYM1 and ZMYM6 do not. By systematic truncation of the zinc fingers of ZMYM3 I also demonstrate that the first zinc finger mediates its interaction with TFII-I, while the eighth and ninth zinc fingers are each sufficient for its interaction with LDS1, HDAC2 and CoREST. These interaction sites implicate ZMYM3 as a novel type of scaffold protein mediating interactions between deacetylase, demethylase and RNase H-type enzymes. To better understand the function of ZMYM3, I generate a ZMYM3 knock-out mouse embryonic stem cell line, and show that ZMYM3 is not required for cell viability or DNA repair, and is not cell-cycle regulated. Given the association of ZMYM3 with various regulators of transcription, I hypothesised that ZMYM3 might be involved in regulating a set of transcripts through these associations. To test this, I compare the transcriptomes of ZMYM3 knock-out and wild-type mouse embryonic stem cell lines by RNA-Seq. While deletion of ZMYM3 has no effect on transcription globally in this context, ZMYM3-null cells express lower levels of the primary transcript of microRNA 142, a specific target of the AGS-associated dsRNA deaminase ADAR1. To better understand the *in vivo* function of ZMYM3, an ES cell line with a ZMYM3 exon flanked by loxP sites is generated, to allow the conditional deletion of ZMYM3 in a whole organism. The association of deacetylase, demethylase and RNase H-type enzymes raises the possibility that histone modification and degradation of DNA-RNA hybrids may be coordinated, and is therefore of potential importance for the field of chromatin biology. As the roles of these associations remain unknown, several functional models of these interactions are proposed, with a discussion of the possible reasons why disruption of these interactions may result in Aicardi–Goutières syndrome

Aicardi-Goutières Syndrome associated mutations of RNase H2B impair its interaction with ZMYM3 and the CoREST histone-modifying complex.

DNA-RNA hybrids arise in all cell types, and are removed by multiple enzymes, including the trimeric ribonuclease, RNase H2. Mutations in human RNase H2 result in Aicardi-Goutières syndrome (AGS), an inflammatory brain disorder notable for being a Mendelian mimic of congenital viral infection. Previous studies have shown that several AGS-associated mutations of the RNase H2B subunit do not affect trimer stability or catalytic activity and are clustered on the surface of the complex, leading us to speculate that these mutations might impair important interactions of RNase H2 with so far unidentified proteins. In this study, we show that AGS mutations in this cluster impair the interaction of RNase H2 with several members of the CoREST chromatin-silencing complex that include the histone deacetylase HDAC2 and the demethylase KDM1A, the transcriptional regulators RCOR1 and GTFII-I as well as ZMYM3, an MYM-type zinc finger protein. We also show that the interaction is mediated by the zinc finger protein ZMYM3, suggesting that ZMYM3 acts as a novel type of scaffold protein coordinating interactions between deacetylase, demethylase and RNase H type enzymes, raising the question of whether coordination between histone modifications and the degradation of RNA-DNA hybrids may be required to prevent inflammation in humans