An Additive Model of Engagement: Considering The Role of Front-End Criminal Justice Agencies in Treatment Provisions [Interim Report: Year Two]

This report provides the initial findings of Year 2 of a multi year project to understand the effects of successive drug policy efforts in Oregon, with special focus given to Ballot Measure 110 (M110). This report uses criminal justice metrics (e.g., arrests and drug court participation) and treatment resource information (e.g., number of individuals served through M110 monies) to better understand how individuals are connecting with services in Oregon, and the role that the criminal justice system can play as one component of a larger network. Related Reports: Key Points in Preparation for Oregon Legislative Session (2024): Examining the Multifaceted Impacts of Drug Decriminalization on Public Safety, Law Enforcement, and Prosecutorial Discretion (December 2023) Impacts of Successive Drug Legislation Shifts: Qualitative Observations from Oregon Law Enforcement [Interim Report: Year On

Key Points in Preparation for Oregon Legislative Session (2024): Examining the Multifaceted Impacts of Drug Decriminalization on Public Safety, Law Enforcement, and Prosecutorial Discretion

These findings are part of a 3-year study to examine the impacts of possession of PCS law changes on: (1) law enforcement discretion, (2) prosecutorial decision-making, (3) courts/sentencing, and (4) public safety. The key findings, unless noted, represent statewide trends and impacts. Prior to M110, other statewide changes in policy, law, and historical events such as the COVID-19 lockdown/court backlog and public defense crisis also had important impacts on enforcement, prosecution/sentencing, and public safety outcomes. As such, data collected during the early implementation of M110 is not likely a reliable predictor of its ultimate impact. The data reported on below is through 1 – 2 years post-M110. Although it sheds light on important questions, it is too early to draw any definitive conclusions about long-term impacts of M110. Link to Year One Report: https://archives.pdx.edu/ds/psu/4011

Public Perceptions Regarding the Use of Force by Police in Portland, Oregon

The current study sought to assess public perceptions regarding the frequency of force used by Portland police and determine whether these beliefs are consistent with officially recorded data on force used by officers in recent years

Impacts of Successive Drug Legislation Shifts: Qualitative Observations from Oregon Law Enforcement [Interim Report: Year One]

This report provides the initial findings of Year 1 of a multi year project to understand the effects of successive drug policy efforts in Oregon, with special focus given to Ballot Measure 110 (M110)

Whole Exome Sequencing Identifies Rare Protein-Coding Variants in Behçet's Disease

Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent. METHODS: Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches. RESULTS: Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein-damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10(-4) and P = 5.16 × 10(-4) , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni-corrected P = 5.63 × 10(-14) , P = 7.29 × 10(-6) , P = 1.15 × 10(-5) , and P = 6.40 × 10(-3) , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant. CONCLUSION: We used whole exome sequencing in BD for the first time and identified 2 rare putative protein-damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD

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

Leveraging Genetic Findings for Precision Medicine in Vasculitis

Vasculitides are a heterogeneous group of low frequent disorders, mainly characterized by the inflammation of blood vessels that narrows or occlude the lumen and limits the blood flow, leading eventually to significant tissue and organ damage. These disorders are classified depending on the size of the affected blood vessels in large, medium, and small vessel vasculitis. Currently, it is known that these syndromes show a complex etiology in which both environmental and genetic factors play a major role in their development. So far, these conditions are not curable and the therapeutic approaches are mainly symptomatic. Moreover, a percentage of the patients do not adequately respond to standard treatments. Over the last years, numerous genetic studies have been carried out to identify susceptibility loci and biological pathways involved in vasculitis pathogenesis as well as potential genetic predictors of treatment response. The ultimate goal of these studies is to identify new therapeutic targets and to improve the use of existing drugs to achieve more effective treatments. This review will focus on the main advances made in the field of genetics and pharmacogenetics of vasculitis and their potential application for ameliorating long-term outcomes in patient management and in the development of precision medicine.This work was supported by the following grants: PI18/00040 from Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Economy, Industry, and Competitiveness) and the Cooperative Research Thematic Network (RETICS) programme (RD16/0012/0013 and RD16/0012/0009) (RIER), from ISCIII (Spanish Ministry of Economy, Industry and Competitiveness)

Post-translational modifications and mass spectrometry detection

In this review, we provide a comprehensive bibliographic overview of the role of mass spectrometry and the recent technical developments in the detection of post-translational modifications (PTMs). We briefly describe the principles of mass spectrometry for detecting PTMs and the protein and peptide enrichment strategies for PTM analysis, including phosphorylation, acetylation and oxidation. This review presents a bibliographic overview of the scientific achievements and the recent technical development in the detection of PTMs is provided. In order to ascertain the state of the art in mass spectrometry and proteomics methodologies for the study of PTMs, we analyzed all the PTM data introduced in the Universal Protein Resource (UniProt) and the literature published in the last three years. The evolution of curated data in UniProt for proteins annotated as being post-translationally modified is also analyzed. Additionally, we have undertaken a careful analysis of the research articles published in the years 2010 to 2012 reporting the detection of PTMs in biological samples by mass spectrometry. © 2013 Elsevier Inc