Cultivating a Culture of Innovative University Engagement for Local Entrepreneurship Development in Rural and Distressed Regions

Abstract Universities are commonly considered to be primary drivers of new innovations, and thus supportive of high-growth knowledge spillover businesses (Audretsch & Lehmann, 2005).  Even the university atmosphere and its embrace of idea exchange can be considered archetypical of a healthy entrepreneurial ecosystem through which innovators act and interact regularly.  However, even with these behavioral advantages on their side, many universities remain focused on developing innovations as outputs of their scholarly efforts, rather than concentrating on the processes of innovation within the university itself.  This is particularly true when it comes to the development of social and community innovations, through which universities can serve as central catalysts of innovation beyond the university borders.  This article presents an alternative perspective of university-based innovation, suggesting that universities must first innovate upon their own culture and institutional structure, revising the role played by the university in the public space.  We suggest that university faculty and staff must step outside their roles and, quite often, allow their academic expertise to take a subordinate role to citizen-driven entrepreneurial expertise in the surrounding community.  Several principles for enhancing this conversation and negotiation between citizen and expert knowledge are presented here, along with ways that universities can embrace public scholarship to fundamentally alter the relationship between experts and citizens.  The article illustrates how to transition from an expert-driven model toward a citizen-expert co-creation model of innovation and entrepreneurship, and draws upon a multiple case study in the U.S. states of Maine, Pennsylvania, and Wisconsin to offer empirical support from the perspective of entrepreneurs.  Our findings are then applied toward envisioning the publicly-engaged university as a potential driver and co-creator in the development of local knowledge and entrepreneurial ventures, especially in lagging and rural regions

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Identifying genetic risk factors for highly heterogeneous disorders such as epilepsy remains challenging. Here we present, to our knowledge, the largest whole-exome sequencing study of epilepsy to date, with more than 54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies and generalized and focal epilepsies, whereas most other gene discoveries are subtype specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single-nucleotide/short insertion and deletion variants, copy number variants and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies