The Theory of Travel Decision-Making: A Conceptual Framework of Active Travel Behavior

We present a unifying conceptual framework of active travel behavior called the theory of travel decision-making. It integrates seminal travel-related concepts from economics, geography, and psychology with active travel behavior theories and empirical research. The framework abstracts an individual’s thought process around short-term travel decisions and explains the roles of activities, built environment factors, socio-demographics, attitudes and perceptions, and habit. Our primary objective is to inform travel behavior research by meeting the need for a theoretical framework capable of guiding studies on active transportation. The framework could also support active transportation planning and analysis methods by informing the development of travel forecasting tools that better represent the unique influences on walking and bicycling. This presentation summarizes the theoretical foundations of active travel behavior; presents and describes the conceptual framework and its components in detail; notes research needs; and assesses the contributions of the framework to active travel behavior theory, research, and practice.https://pdxscholar.library.pdx.edu/trec_seminar/1083/thumbnail.jp

Cycling by Choice or Necessity? Exploring the Gender Gap in Bicycling in Oregon

In Oregon, as elsewhere in the US, a greater percentage of men bicycle than women. This study illuminates the gender gap in bicycling by exploring differences in bicycling among women and men in Oregon. A one-day statewide travel survey of over 30,000 adults was examined. Comparisons between individual, household, and trip and activity characteristics for people grouped by gender (women vs. men) and bicycling (made a bicycle trip or normally commuted by bicycle vs. did not bicycle) were assessed using chi-squared tests of independence. Many significant differences were found. In particular, women living alone, not working, without a high-school degree, without a driver license, and living in low-income households or zero-vehicle households were less likely to bicycle than other women. Men with similar characteristics did not exhibit the same trends and sometimes were even more likely to bicycle. These findings are consistent with a perspective that women who bicycle are more likely to do so by choice, whereas women with fewer means are less likely to turn to bicycling than their male counterparts. In addition, there was partial support for the idea that women’s roles and responsibilities (for household maintenance and escorting, but not necessarily the presence of children) may contribute to this deficit. The study’s results begin to suggest a rethinking of bicycle-promoting policies and interventions to better target certain women, although further research is needed to more fully understand bicycling’s gender gap.https://pdxscholar.library.pdx.edu/trec_seminar/1085/thumbnail.jp

Development of a Pedestrian Demand Estimation Tool: a Destination Choice Model

There is growing support for improvements to the quality of the walking environment, including more investments to promote pedestrian travel. Planners, engineers, and others seek improved tools to estimate pedestrian demand that are sensitive to environmental and demographic factors at the appropriate scale in order to aid policy-relevant issues like air quality, public health, and smart allocation of infrastructure and other resources. Further, in the travel demand forecasting realm, tools of this kind are difficult to implement due to the use of spatial scales of analysis that are oriented towards motorized modes, vast data requirements, and computer processing limitations. To address these issues, a two-phase project between Portland State University and Oregon Metro is underway to develop a robust pedestrian planning method for use in regional travel demand models. The first phase, completed in 2013, utilizes a tool that predicts the number of walking trips generated with spatial acuity, based on a new measure of the pedestrian environment and a micro-level unit of analysis. Currently, phase two is building upon this tool to predict the distribution of walking trips, connecting the origins predicted in phase one to destinations. This presentation will focus on phase two, which is one of the first studies to focus on destination choices among pedestrians separately from other modes. The approach can be extended to identify the spatial extent of potential pedestrian paths to these destinations. Ultimately, the products developed from the research can estimate various aspects of pedestrian demand – trip generation, trip distribution, and areas of potential pedestrian activity. These tools will add to the analytical methods available for transportation modeling, pedestrian and safety analysis, health assessments, and other pedestrian planning applications

Development of a Pedestrian Demand Estimation Tool: a Destination Choice Model

There is growing support for improvements to the quality of the walking environment, including more investments to promote pedestrian travel. Planners, engineers, and others seek improved tools to estimate pedestrian demand that are sensitive to environmental and demographic factors at the appropriate scale in order to aid policy-relevant issues like air quality, public health, and smart allocation of infrastructure and other resources. Further, in the travel demand forecasting realm, tools of this kind are difficult to implement due to the use of spatial scales of analysis that are oriented towards motorized modes, vast data requirements, and computer processing limitations. To address these issues, a two-phase project between Portland State University and Oregon Metro is underway to develop a robust pedestrian planning method for use in regional travel demand models. The first phase, completed in 2013, utilizes a tool that predicts the number of walking trips generated with spatial acuity, based on a new measure of the pedestrian environment and a micro-level unit of analysis. Currently, phase two is building upon this tool to predict the distribution of walking trips, connecting the origins predicted in phase one to destinations. This presentation will focus on phase two, which is one of the first studies to focus on destination choices among pedestrians separately from other modes. The approach can be extended to identify the spatial extent of potential pedestrian paths to these destinations. Ultimately, the products developed from the research can estimate various aspects of pedestrian demand – trip generation, trip distribution, and areas of potential pedestrian activity. These tools will add to the analytical methods available for transportation modeling, pedestrian and safety analysis, health assessments, and other pedestrian planning applications

Extracellular Vesicles from Caveolin-Enriched Microdomains Regulate Hyaluronan-Mediated Sustained Vascular Integrity

Defects in vascular integrity are an initiating factor in several disease processes. We have previously reported that high molecular weight hyaluronan (HMW-HA), a major glycosaminoglycan in the body, promotes rapid signal transduction in human pulmonary microvascular endothelial cells (HPMVEC) leading to barrier enhancement. In contrast, low molecular weight hyaluronan (LMW-HA), produced in disease states by hyaluronidases and reactive oxygen species (ROS), induces HPMVEC barrier disruption. However, the mechanism(s) of sustained barrier regulation by HA are poorly defined. Our results indicate that long-term (6–24 hours) exposure of HMW-HA induced release of a novel type of extracellular vesicle from HLMVEC called enlargeosomes (characterized by AHNAK expression) while LMW-HA long-term exposure promoted release of exosomes (characterized by CD9, CD63, and CD81 expression). These effects were blocked by inhibiting caveolin-enriched microdomain (CEM) formation. Further, inhibiting enlargeosome release by annexin II siRNA attenuated the sustained barrier enhancing effects of HMW-HA. Finally, exposure of isolated enlargeosomes to HPMVEC monolayers generated barrier enhancement while exosomes led to barrier disruption. Taken together, these results suggest that differential release of extracellular vesicles from CEM modulate the sustained HPMVEC barrier regulation by HMW-HA and LMW-HA. HMW-HA-induced specialized enlargeosomes can be a potential therapeutic strategy for diseases involving impaired vascular integrity

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once