Effects of Transit Signal Priority on Traffic Safety: Interrupted Time Series Analysis of Portland, Oregon, Implementations

Transit signal priority (TSP) has been implemented to transit systems in many cities of the United States. In evaluating TSP systems, more attention has been given to its operational effects than to its safety effects. Existing studies assessing safety effects of TSP reported mixed results, indicating that the safety effects of TSP vary in different contexts. In this study, TSP implementations in Portland, Oregon, were assessed using interrupted time series analysis (ITSA) on month-to-month changes in number of crashes from January 1995 to December 2010. Single-group and controlled ITSA were conducted for all crashes, property-damage-only crashes, fatal and injury crashes, pedestrian-involved crashes, and bike-involved crashes. Evaluation of the post-intervention period (2003 to 2010) showed a reduction in all crashes on street sections with TSP (-4.5 percent), comparing with the counterfactual estimations based on the control group data. The reduction in property-damage-only crashes (-10.0 percent) contributed the most to the overall reduction. Fatal and injury crashes leveled out after TSP implementation but did not change significantly comparing with the control group. Pedestrian and bike-involved crashes were found to increase in the post-intervention period with TSP, comparing with the control group. Potential reasons to these TSP effects on traffic safety were discussed.Comment: Published in Accident Analysis & Preventio

Large-scale pathway specific polygenic risk and transcriptomic community network analysis identifies novel functional pathways in Parkinson disease

Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson’s Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson’s disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal–lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done

Parkinson’s disease determinants, prediction and gene-environment interactions in the UK Biobank

Objective: To systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores. Methods: We identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene–environment interactions and compare predictive models for PD. Results: Strong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes. Interpretation: Here, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene–environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD

Optimising classification of Parkinson’s disease based on motor, olfactory, neuropsychiatric and sleep features

Olfactory loss, motor impairment, anxiety/depression, and REM-sleep behaviour disorder (RBD) are prodromal Parkinson’s disease (PD) features. PD risk prediction models typically dichotomize test results and apply likelihood ratios (LRs) to scores above and below cut-offs. We investigate whether LRs for specific test values could enhance classification between PD and controls. PD patient data on smell (UPSIT), possible RBD (RBD Screening Questionnaire), and anxiety/depression (LADS) were taken from the Tracking Parkinson’s study (n = 1046). For motor impairment (BRAIN test) in PD cases, published data were supplemented (n = 87). Control data (HADS for anxiety/depression) were taken from the PREDICT-PD pilot study (n = 1314). UPSIT, RBDSQ, and anxiety/depression data were analysed using logistic regression to determine which items were associated with PD. Gaussian distributions were fitted to BRAIN test scores. LRs were calculated from logistic regression models or score distributions. False-positive rates (FPRs) for specified detection rates (DRs) were calculated. Sixteen odours were associated with PD; LRs for this set ranged from 0.005 to 5511. Six RBDSQ and seven anxiety/depression questions were associated with PD; LRs ranged from 0.35 to 69 and from 0.002 to 402, respectively. BRAIN test LRs ranged from 0.16 to 1311. For a 70% DR, the FPR was 2.4% for the 16 odours, 4.6% for anxiety/depression, 16.0% for the BRAIN test, and 20.0% for the RBDSQ. Specific selections of (prodromal) PD marker features rather than dichotomized marker test results optimize PD classification. Such optimized classification models could improve the ability of algorithms to detect prodromal PD; however, prospective studies are needed to investigate their value for PD-prediction models

The impact of COVID-19 on access to Parkinson’s disease medication

Background: Many countries have implemented drastic measures to fight the COVID‐19 pandemic. Restrictions and diversion of resources may have negatively affected patients with Parkinson's disease (PD). Our aim was to examine whether COVID‐19 had an impact on access to PD medication by region and income. Methods: This study was conducted as part of a survey sent to members of the Movement Disorders Society focusing on access to PD medication globally. Results: Of 346 responses, 157 (45.4%) agreed that COVID‐19 had affected access to PD medication, while 189 (54.6%) disagreed. 22.8% of high‐income and 88.9% of low‐income countries' respondents agreed that access to PD medication was affected by COVID‐19. 59% of all ‘yes' respondents reported increased disability of patients as an impact. Conclusions: Access to PD medication is likely to have been affected by COVID‐19 and result in deterioration of patients' symptomatic control. Resource‐poor countries appear to be disproportionately affected compared to more affluent countries. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Type 2 diabetes as a determinant of Parkinson's disease risk and progression

Background: Type 2 diabetes (T2DM) and Parkinson's disease (PD) are prevalent diseases that affect an aging population. Previous systematic reviews and meta-analyses have explored the relationship between diabetes and the risk of PD, but the results have been conflicting. Objective: The objective was to investigate T2DM as a determinant of PD through a meta-analysis of observational and genetic summary data. Methods: A systematic review and meta-analysis of observational studies was undertaken by searching 6 databases. We selected the highest-quality studies investigating the association of T2DM with PD risk and progression. We then used Mendelian randomization (MR) to investigate the causal effects of genetic liability toward T2DM on PD risk and progression, using summary data derived from genome-wide association studies. Results: In the observational part of the study, pooled effect estimates showed that T2DM was associated with an increased risk of PD (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07–1.36), and there was some evidence that T2DM was associated with faster progression of motor symptoms (standardized mean difference [SMD] 0.55, 95% CI 0.39–0.72) and cognitive decline (SMD −0.92, 95% CI −1.50 to −0.34). Using MR, we found supportive evidence for a causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR 1.08, 95% CI 1.02–1.14; P = 0.010) and some evidence of an effect on motor progression (IVW OR 1.10, 95% CI 1.01–1.20; P = 0.032) but not on cognitive progression. Conclusions: Using meta-analyses of traditional observational studies and genetic data, we observed convincing evidence for an effect of T2DM on PD risk and new evidence to support a role in PD progression

A Taste of Progress: The Temperance Movement and its influence on Food and Drink and the Urban Landscape at the time of the International Exhibitions in the Australian Colonies

International Exhibitions were very much part of the cultural scene in the second half of the nineteenth century. They provided nations with opportunities to demonstrate their artistic, industrial and agricultural innovations and ingenuity and to encourage trade relations. The Australian colonies joined the fray and staged eight International Exhibitions in the latter half of the nineteenth century, three of which were significant—Sydney in 1879 and two in Melbourne in 1880 and 1888. Food and drink played a crucial role in the lived experience for visitors to the Exhibitions and warrants more attention. In particular, the exhibitions in the Australian colonies occurred at a time when the prohibition of alcohol was seriously debated in Australia. To accommodate and feed inter-colonial and international visitors to the Exhibitions, wealthy members of the temperance movement (a worldwide lobby group) that reached a highpoint in the latter part of the nineteenth century, constructed ‘coffee palaces’ on a grand scale. These majestic alcohol-free hotels were seen as an alternative to licensed hotels. They became an integral part of Australia’s urban, social and cultural landscape as the push to control alcohol consumption gathered momentum. However, at the same time as the temperance movement gained momentum so too did Australia’s burgeoning wine industry.Some commentators such as the Reverend John Ignatius Bleasedale (1822-84), encouraged Victorians to be “a healthy, sober, jolly, wine-drinking population”, and in New South Wales, the colonial government in an attempt to wean people away from spirits enabled the establishment of many a “Colonial Wine Shop” (Walsh). At the Exhibitions, the Australian wine industry was to be accommodated and encouraged at all costs. The apparent contradiction between the ideology of temperance and the economics of intemperance appears to have been bridged quite successfully at the time of the Exhibitions.Food and drink served at the Exhibitions and coffee palaces stood as a powerful semiotic device for communicating and maintaining conceptions of identity, history, traditions and progress, and of inclusion and exclusion—it served to bind individuals to society as well as expressing power relations and struggles