Translating genetic and preclinical findings into autism therapies

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations on cellular function leading to disease. Efforts to translate these findings into successful therapies have yet to bear fruit. We discuss how the valuable insight into the disorder provided by these new models can be used to better understand ASD and develop future clinical trials

The effects of “pulling levers” focused deterrence strategies on crime

A number of American police departments have been experimenting with new problem-oriented policing frameworks to prevent gang and group-involved violence generally known as the “pulling levers” focused deterrence strategies. Focused deterrence strategies honor core deterrence ideas, such as increasing risks faced by offenders, while finding new and creative ways of deploying traditional and non-traditional law enforcement tools to do so, such as directly communicating incentives and disincentives to targeted offenders. Pioneered in Boston to halt serious gang violence, the focused deterrence framework has been applied in many American cities through federally sponsored violence prevention programs. In its simplest form, the approach consists of selecting a particular crime problem, such as gang homicide; convening an interagency working group of law enforcement, social-service, and community-based practitioners; conducting research to identify key offenders, groups, and behavior patterns; framing a response to offenders and groups of offenders that uses a varied menu of sanctions (“pulling levers”) to stop them from continuing their violent behavior; focusing social services and community resources on targeted offenders and groups to match law enforcement prevention efforts; and directly and repeatedly communicating with offenders to make them understand why they are receiving this special attention. These new strategic approaches have been applied to a range of crime problems, such as overt drug markets and individual repeat offenders, and have shown promising results in the reduction of crime. Objectives: To synthesize the extant evaluation literature and assess the effects of pulling levers focused deterrence strategies on crime. Conclusions: We conclude that pulling levers focused deterrence strategies seem to be effective in reducing crime. However, we urge caution in interpreting these results because of the lack of more rigorous randomized controlled trials in the existing body of scientific evidence on this approach

Creative New York 2005

Examines the economic importance of New York's nonprofit arts, cultural organizations, and for-profit creative companies, and explores strategies for maintaining the city's arts preeminence in the face of intense competition from other cities

Current Perspectives in Autism Spectrum Disorder: From Genes to Therapy.

Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with high heritability and both phenotypic and genetic heterogeneity. To date, mutations in hundreds of genes have been associated to varying degrees with increased ASD risk. A better understanding of the functions of these genes and whether they fit together in functional groups or impact similar neuronal circuits is needed to develop rational treatment strategies. We will review current areas of emphasis in ASD research, starting from human genetics and exploring how mouse models of human mutations have helped identify specific molecular pathways (protein synthesis and degradation, chromatin remodeling, intracellular signaling), which are linked to alterations in circuit function and cognitive/social behavior. We will conclude by discussing how we can leverage the findings on molecular and cellular alterations found in ASD to develop therapies for neurodevelopmental disorders

On Crowd-verification of Biological Networks

Biological networks with a structured syntax are a powerful way of representing biological information generated from high density data; however, they can become unwieldy to manage as their size and complexity increase. This article presents a crowd-verification approach for the visualization and expansion of biological networks. Web-based graphical interfaces allow visualization of causal and correlative biological relationships represented using Biological Expression Language (BEL). Crowdsourcing principles enable participants to communally annotate these relationships based on literature evidences. Gamification principles are incorporated to further engage domain experts throughout biology to gather robust peer-reviewed information from which relationships can be identified and verified. The resulting network models will represent the current status of biological knowledge within the defined boundaries, here processes related to human lung disease. These models are amenable to computational analysis. For some period following conclusion of the challenge, the published models will remain available for continuous use and expansion by the scientific community