Development of a Multi-Class Bicyclist Route Choice Model Using Revealed Preference Data

Existing regional travel forecasting systems are not typically set up to forecast usage of bicycle infrastructure and are insensitive to bicyclists\u27 route preferences in general. We collected revealed preference, GPS data on 162 bicyclists over the course of several days and coded the resulting trips to a highly detailed bicycle network model. We then use these data to estimate bicyclist route choice models. As part of this research, we developed a sophisticated choice set generation algorithm based on multiple permutations of labeled path attributes, which seems to out-perform comparable implementations of other route choice set generation algorithms. The model was formulated as a Path-Size Logit model to account for overlapping route alternatives. The estimation results show compelling intuitive elasticities for route choice attributes, including the effects of distance and delay; avoiding high-volumes of vehicular traffic, stops and turns, and elevation gain; and preferences for certain bike infrastructure types, particularly at bridge crossings and off-street paths. Estimation results also support segmentation by commute versus non-commute trip types, but are less clear when it comes to gender. The final model will be implemented as part of the regional travel forecasting system for Portland, Oregon, U.S.A

Factors Influencing Bike Share Among Underserved Populations: Evidence from Three US Cities

There is evidence that lower-income and people of color (POC) in the U.S. do not use bike share as much as higher-income and white people. Using data from residents living near stations in New York, Chicago, and Philadelphia, our analysis examines reasons for these disparities. While smaller shares of POC are members (vs higher-income white people), large shares of POC are interested in bike share. Among POC, having positive attitudes about bicycling and having family and friends that use bike share are strong predictors of interest in bike share. POC are also motivated to use bike share for recreational reasons. Receiving information from interactive sources may be effective at increasing bike share use and interest, though it is not clear whether these efforts have affected POC. Cost is a barrier for people who have tried bike share and are interested in using it in the future but are not members

Usability and Reliability of Smart Glasses for Secondary Triage During Mass Casualty Incidents

Wearable smart glasses like Google Glass provide real-time video and image transmission to remote viewers. The use of Google Glass and other Augmented Reality (AR) platforms in mass casualty incidents (MCIs) can provide incident commanders and physicians at receiving hospitals real-time data regarding injuries sustained by victims at the scene. This real-time data is critical to allocation of hospital resources prior to receiving victims of a MCI. Remote physician participation in real-time MCI care prior to victims’ hospital arrival may improve triage, and direct emergency and critical care services to those most in need. We report the use of Google Glass among first responders to transmit real-time data from a simulated MCI to allow remote physicians to complete augmented secondary triage

Paramedic Pain Management Practice with Introduction of a Non-opiate Treatment Protocol

INTRODUCTION: There is concern about the initiation of opiates in healthcare settings due to the risk of future misuse. Although opiate medications have historically been at the core of prehospital pain management, several states are introducing non-opiate alternatives to prehospital care. Prior studies suggest that non-opiate analgesics are non-inferior to opiates for many acute complaints, yet there is little literature describing practice patterns of pain management in prehospital care. Our goal was to describe the practice patterns and attitudes of paramedics toward pain management after the introduction of non-opiates to a statewide protocol. METHODS: This study was two-armed. The first arm employed a pre/post retrospective chart review model examining medication administrations reported to the Massachusetts Ambulance Trip Information System between January 1, 2017-December 31, 2018. We abstracted instances of opiate and non-opiate utilizations along with patients\u27 clinical course. The second arm consisted of a survey administered to paramedics one year after implementation of non-opiates in the state protocol, which used binary questions and Likert scales to describe beliefs pertaining to prehospital analgesia. RESULTS: Pain medications were administered in 1.6% of emergency medical services incidents in 2017 and 1.7% of incidents in 2018. The rate of opiate analgesic use was reduced by 9.4% in 2018 compared to 2017 (90.6% vs 100.0%). The absolute reduction in opiate use in 2018 was 3.6%. Women were less likely (odds ratio [OR] = 0.78, 95% confidence interval [CI], 0.69-0.89) and trauma patients were more likely to receive opiates (OR = 2.36, CI, 1.96-2.84). Mean transport times were longer in opiate administration incidents (36.97 vs 29.35 minutes, t = 17.34, p \u3c 0.0001). We surveyed 100 paramedics (mean age 41.98, 84% male). Compositely, 85% of paramedics planned to use non-opiates and 35% reported having done so. Participants planning to use non-opiates were younger and less experienced. Participants indicated that concern about adverse effects, efficacy, and time to effect impacted their practice patterns. CONCLUSION: The introduction of non-opiate pain medication to state protocols led to reduced opiate administration. Men and trauma patients were more likely to receive opiates. Paramedics reported enthusiasm for non-opiate medications. Beliefs about non-opioid analgesics pertaining to adverse effects, onset time, and efficacy may influence their utilization

Augmented Reality Technology to Facilitate Proficiency in Emergency Medical Procedures

Background: Augmented reality (AR) conveys an experience during which the user’s real-time environment is enhanced by computer-generated perceptual information; it is being investigated as a solution to enhance medical education and clinical practice. There is little literature on its utility for teaching emergency procedures. Methods: A within-subjects trial was performed comparing traditional training to AR guidance for two emergency procedures. Lay-subjects and emergency medical technicians received video training and AR guidance for performing bag-valve-mask ventilation and needle-decompression. Subjects performed both procedures in a simulation setting after each training modality. Subject performance, acceptability and usability were analyzed. Results: There was no difference in procedural performance between lay or EMT subjects for AR training, and no difference in subject-reported usefulness between the AR and control training. Conclusion: AR mediated guidance for emergency medical procedures is feasible and efficacious. Subject performance after AR training was statistically undistinguishable from a didactic educational modality

NOS1AP is a novel molecular target and critical factor in TDP-43 pathology

Cappelli et al. reported that Nitric Oxide Synthase 1 Adaptor Protein is a co-regulated transcript of the TAR DNA-binding protein 43 kDa, reduced in amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients with TAR DNA-binding protein 43 kDa pathology. Overall, their results highlight Nitric Oxide Synthase 1 Adaptor Protein as a novel druggable disease-relevant gene in TAR DNA-binding protein 43 kDa-related proteinopathies.Many lines of evidence have highlighted the role played by heterogeneous nuclear ribonucleoproteins in amyotrophic lateral sclerosis. In this study, we have aimed to identify transcripts co-regulated by TAR DNA-binding protein 43 kDa and highly conserved heterogeneous nuclear ribonucleoproteins which have been previously shown to regulate TAR DNA-binding protein 43 kDa toxicity (deleted in azoospermia-associated protein 1, heterogeneous nuclear ribonucleoprotein -Q, -D, -K and -U). Using the transcriptome analyses, we have uncovered that Nitric Oxide Synthase 1 Adaptor Protein mRNA is a direct TAR DNA-binding protein 43 kDa target, and in flies, its modulation alone can rescue TAR DNA-binding protein 43 kDa pathology. In primary mouse cortical neurons, we show that TAR DNA-binding protein 43 kDa mediated downregulation of Nitric Oxide Synthase 1 Adaptor Protein expression strongly affects the NMDA-receptor signalling pathway. In human patients, the downregulation of Nitric Oxide Synthase 1 Adaptor Protein mRNA strongly correlates with TAR DNA-binding protein 43 kDa proteinopathy as measured by cryptic Stathmin-2 and Unc-13 homolog A cryptic exon inclusion. Overall, our results demonstrate that Nitric Oxide Synthase 1 Adaptor Protein may represent a novel disease-relevant gene, potentially suitable for the development of new therapeutic strategies

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

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

The Bacterial and Viral Complexity of Postinfectious Hydrocephalus in Uganda

Postinfectious hydrocephalus (PIH), often following neonatal sepsis, is the most common cause of pediatric hydrocephalus world-wide, yet the microbial pathogens remain uncharacterized. Characterization of the microbial agents causing PIH would lead to an emphasis shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention. We examined blood and CSF from 100 consecutive cases of PIH and control cases of non-postinfectious hydrocephalus (NPIH) in infants in Uganda. Genomic testing was undertaken for bacterial, fungal, and parasitic DNA, DNA and RNA sequencing for viral identification, and extensive bacterial culture recovery. We uncovered a major contribution to PIH from Paenibacillus , upon a background of frequent cytomegalovirus (CMV) infection. CMV was only found in CSF in PIH cases. A facultatively anaerobic isolate was recovered. Assembly of the genome revealed a strain of P. thiaminolyticus . In mice, this isolate designated strain Mbale , was lethal in contrast with the benign reference strain. These findings point to the value of an unbiased pan-microbial approach to characterize PIH in settings where the organisms remain unknown, and enables a pathway towards more optimal treatment and prevention of the proximate neonatal infections. One Sentence Summary We have discovered a novel strain of bacteria upon a frequent viral background underlying postinfectious hydrocephalus in Uganda

Paenibacillus infection with frequent viral coinfection contributes to postinfectious hydrocephalus in Ugandan infants

Postinfectious hydrocephalus (PIH), which often follows neonatal sepsis, is the most common cause of pediatric hydrocephalus worldwide, yet the microbial pathogens underlying this disease remain to be elucidated. Characterization of the microbial agents causing PIH would enable a shift from surgical palliation of cerebrospinal fluid (CSF) accumulation to prevention of the disease. Here, we examined blood and CSF samples collected from 100 consecutive infant cases of PIH and control cases comprising infants with non-postinfectious hydrocephalus in Uganda. Genomic sequencing of samples was undertaken to test for bacterial, fungal, and parasitic DNA; DNA and RNA sequencing was used to identify viruses; and bacterial culture recovery was used to identify potential causative organisms. We found that infection with the bacterium Paenibacillus, together with frequent cytomegalovirus (CMV) coinfection, was associated with PIH in our infant cohort. Assembly of the genome of a facultative anaerobic bacterial isolate recovered from cultures of CSF samples from PIH cases identified a strain of Paenibacillus thiaminolyticus. This strain, designated Mbale, was lethal when injected into mice in contrast to the benign reference Paenibacillus strain. These findings show that an unbiased pan-microbial approach enabled characterization of Paenibacillus in CSF samples from PIH cases, and point toward a pathway of more optimal treatment and prevention for PIH and other proximate neonatal infections