16 research outputs found
Adapting to Leadership in Offshore Schools: A Case Study of Sino-Nova Scotian Schools
A mixed-methods study including 22 Sino-Nova Scotian school principals in China has established that preparation for leadership in that context requires the consideration of many salient factors. While many North American standards of leadership are an important foundation, effective communication within the multidimensional system is of paramount importance. It was also found that, in order to administer a successful program, principals needed to build stronger social support systems for their teachers and further create a community of practice that included cultural sensitivity and understanding
Preparing Instructional Leaders: Evaluating a Regional Program to Gauge Perceived Effectiveness
An instructional leadership program (ILP) has offered education and support to three cohorts of educational leaders in Nova Scotia, Canada, amounting to approximately 130 participants. Quantitative and qualitative feedback from a convenience sample (n = 90) suggests that the ILP offers an extremely useful practical program; in fact, 95 percent of the sample indicates advances in the categories of professional growth, improved instructional leadership, and tangible progress in administrative effectiveness. Systemic and school environment trends have dictated that educational leaders need a skill set that positions them to respond more aptly to issues of poverty, socioemotional health, and mental health while attending to improved community building both within the school and in the greater public. This study uses surveys, interviews, and focus groups to identify emerging and impending challenges
Education Research in the Canadian Context
This special issue of the International Journal of Education Policy & Leadership (IJEPL), Research in the Canadian Context, marks a significant milestone for the journal. Throughout our twelve-year history, we have sought to publish the best research in leadership, policy, and research use, allowing authors to decide the topics by dint of their research. While this model still serves as the foundation for IJEPL content, we decided to give researchers a chance to engage in deeper conversations by introducing special issues. In our first special issue, researchers discuss their work within the scope of education policy, leadership, and research use within the Canadian context. While many aspects of leadership, teaching, and learning can be seen as similar across contexts, there are also issues of particular concern within national, regional, provincial, or local spheres, particularly when looking at policy and system changes. The researchers featured in this issue provide an important look into education in Canada.PolicyIn the policy realm, Sue Winton and Lauren Jervis examine a 22-year campaign to change special education assessment policy in Ontario, examining how discourses dominant in the province enabled the government to leave the issue unresolved for decades. Issues of access and equity play out within a neoliberal context focused on individualism, meritocracy, and the reduced funding of public services. While Winton and Jervis highlight the tension between policy goals and ideological contexts, Jean-Vianney Auclair considers the place of policy dialogues within governmental frames, and the challenge of engaging in broadly applicable work within vertically structured governmental agencies. One often-touted way to move beyondResearch useWithin the scope of research use, Sarah L. Patten examines how socioeconomic status (SES) is defined and measured in Canada, the challenges in defining SES, and potential solutions specific to the Canadian context. In looking at knowledge mobilization, Joelle Rodway considers how formal coaches and informal social networks nserve to connect research, policy, and practice in Ontario’s Child and Youth Mental Health program.LeadershipTurning to leadership, contributing researchers explored the challenges involved in staff development, administrator preparation, and student outcomes. Keith Walker and Benjamin Kutsyuruba explore how educational administrators can support early career teachers to increase retention, and the somewhat haphazard policies and supports in place across Canada to bring administrators and new teachers together. Gregory Rodney MacKinnon, David Young, Sophie Paish, and Sue LeBel look at how one program in Nova Scotia conceptualizes professional growth, instructional leadership, and administrative effectiveness and the emerging needs of administrators to respond to issues of poverty, socioemotional health, and mental health, while also building community. This complex environment may mean expanding leadership preparation to include a broader consideration of well-being and community. Finally, Victoria Handford and Kenneth Leithwood look at the role school leaders play in improving student achievement in British Columbia, and the school district characteristics associated with improving student achievement.Taken together, the research in this special issue touches on many of the challenges in policy development, application, and leadership practice, and the myriad ways that research can be used to address these challenges. We hope you enjoy this first special issue of IJEPL
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia
Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Signaling, Bidding and the Final Price in the Online Auction Platform Almost Without Information Asymmetry: An Empirical Study on China's Largest B2C Marketplace
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60-80%(1), much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factorSP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.11Nsciescopu