AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma

A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts. Co-mutation analysis identified co-occurring driver combinations such as B2m-Nf1, Mll3-Nf1 and Zc3h13-Rb1, which were subsequently validated using AAV minipools. Distinct from Nf1-mutant tumors, Rb1-mutant tumors are undifferentiated and aberrantly express homeobox gene clusters. The addition of Zc3h13 or Pten mutations altered the gene expression profiles of Rb1 mutants, rendering them more resistant to temozolomide. Our study provides a functional landscape of gliomagenesis suppressors in vivo

Getting Proactive with Police Proactivity: the Benefits of Computer-Aided Dispatch for Directing Police Resources to Areas of Need

Sherman et al. [Sherman, L. W., Williams, S., Ariel, B., et al. (2014). ‘An Integrated Theory of Hot Spots Patrol Strategy Implementing Prevention by Scaling up and Feeding Back.’ Journal of Contemporary Criminal Justice 30(2): 95–122.] argue that crime reductions associated with hot spot policing can be maximized by carefully managing the dosage of supplemental resources delivered. Fully achieving this goal in prior studies has been difficult due to resistance by officers, the use of atypical strategies for directing patrols to target locations, and insufficient attention to the measurement of treatment dosages. This has led to calls for process research examining the implementation of hot spot policing in law enforcement agencies. The current study represents one such effort. The computer-aided dispatch (CAD) system for a large US police department was pre-programmed with 16,200 supplemental community engagement patrols that were communicated to officers similar to emergency calls for service generated by the public. An interdisciplinary team comprised sworn officers, crime analysts, and academics designed and evaluated the intervention using an experimental design. The team found that the vast majority of patrols were delivered as scheduled (n = 12,965; 80.0%) and that planned dosage ratios between treatment conditions were achieved. Advantages of using CAD for proactive policing initiatives and benefits of police–academic partnerships are discussed

Social bias in the policing of illicit drug users in the UK and

This paper uses data from the Global Drug Survey to test the hypothesis that there is social bias in the policing of drug users, in the form of stop and search for drugs. The Global Drug Survey is a self-report, internet survey. In 2012, it included a non-random sample of illicit drug users in the UK (n=5,919) and Australia (n=5,707). We discuss previous research on social bias in policing. We argue that an intersectional approach is necessary in order to analyse patterns of stop and search for drugs across drug users who have various social statuses. In order to analyse the influence of various patterns of drug use, we create an inductive typology of a wide range of drug use types and temporalities, using latent class analysis. We use these latent classes, frequency of past month drug use and indicators of drug dependency alongside sociodemographic variables in binary logistic regression analyses of the odds of reporting being stopped and searched for drugs in the past year. We use these models to test both consensus and conflict perspectives on the policing of drug users. We find support for both perspectives in both countries. Patterns of drug use do significantly predict the odds of sampled drug users reporting police stop and search, as expected by the consensus perspective. But drug users who were younger, male and of less advantaged social status (as measured by education in the UK sample, and by minority ethnicity, income and unemployment in the Australian sample) also had significantly higher odds of reporting stop and search. This supports the conflict perspective on policing and our hypothesis that there is evidence of social bias in the policing of drug users in the Global Drug Survey sample