Testing and Evaluation of MASH TL-3 Transition Between Guardrail and Portable Concrete Barriers

Three full-scale vehicle crash tests were conducted according to the Manual for Assessing Safety Hardware (MASH) Test Level 3 (TL-3) safety performance criteria on a transition between the Midwest Guardrail System (MGS) and a portable concrete barrier (PCB) system. The transition system utilized for test nos. MGSPCB-1 through MGSPCB-3 consisted of a standard MGS that overlapped a series of F- shape PCB segments that approached the MGS at a 15H:1V flare. In the overlapped portion of the barrier systems, uniquely-designed blockout holders and a specialized W-beam end shoe mounting bracket were used to connect the systems. In test no. MGSPCB-1, a 5,079-lb (2,304-kg) pickup truck impacted the barrier at 63.2 mph (101.8 km/h) and 25.3 degrees. The barrier captured and redirected the 2270P vehicle, and the vehicle decelerations were within the recommended occupant risk limits. In test no. MGSPCB-2, a 2,601-lb (1,180-kg) car impacted the barrier at 65.1 mph (104.8 km/h) and 24.0 degrees. The barrier captured and redirected the 1100C vehicle, and the vehicle decelerations were within the recommended occupant risk limits. In test no. MGSPCB-3, a 5,177-lb (2,348-kg) pickup truck impacted the barrier at 63.1 mph (101.5 km/h) and 24.6 degrees. For this test, the system was impacted in the reverse direction. The barrier captured and redirected the 2270P vehicle, and the vehicle decelerations were within the recommended occupant risk limits. Based on the results of these successful crash tests, it is believed that the transition design detailed herein represents the first MASH TL- 3 crashworthy transition between the MGS and PCBs

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia

Correction to: Nature Genetics https://doi.org/10.1038/s41588-022-01192-y. Published online 20 October 2022. In the version of this article originally published, a paragraph was omitted in the Methods section, reading “Genomic control. Top SNPs are reported from the more conservative GWAS results adjusted for genomic control (Fig. 1, Extended Data Figs. 1–4, and Supplementary Tables 1, 2, 9 and 10), whereas downstream analyses (including gene-set analysis, enrichment and heritability partitioning, genetic correlations, polygenic prediction, candidate gene replication) are based on GWAS results without genomic control.” The paragraph has now been included in the HTML and PDF versions of the article

Genome-wide association study of {REM} sleep behavior disorder identifies polygenic risk and brain expression effects

AbstractRapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Midwest Guardrail System (MGS) with an Omitted Post

The objective of this research study was to evaluate the MGS (31” tall W-beam guardrail) with an omitted post according to the safety performance criteria provided in MASH. A single full-scale crash test was conducted with the 2270P pickup truck in accordance with MASH test no. 3-11. The small car test, test no. 3-10, was deemed unnecessary as the pickup truck test would result in higher rail loads, a greater propensity for rail rupture, and a greater risk of failure. The test installation utilized standard 6-ft (1.8-m) long steel guardrail posts with 12-in. (305-mm) deep blockouts. A single post was omitted near the center of the 175-ft (53.3-m) long installation. Test no. MGSMP-1 resulted in the guardrail capturing and smoothly redirecting the 2270P vehicle. The vehicle remained upright, and all vehicle decelerations were within the recommended occupant risk limits. As such, the MGS with an omitted post satisfied the TL-3 safety performance criteria found in MASH. Following the full-scale crash testing, implementation guidance and recommendations were provided regarding the omission of a post within various MGS configurations, including MGS adjacent to 2:1 fill slopes, MGS on 8:1 approach slopes, MGS in combination with curbs, wood post MGS, non-blocked MGS, terminals and anchorages, MGS stiffness transition to thrie beam approach guardrail transitions, and MGS long-span systems

Cable-to-Post Attachments for Use in Non-Proprietary High-Tension Cable Median Barrier – Phase II

The objective of this study was to reevaluate and improve the existing cable-to-post attachment hardware that is utilized in the non-proprietary cable barrier being developed at MwRSF. The study focused on redesigning the bolted, tabbed bracket (V10) to eliminate the bolt, reduce the number of components per bracket, eliminate the need for tools during installation, and reduce the number of small parts. Three attachment concepts were selected for evaluation through dynamic testing: (1) the key plate attachment; (2) the wire lock pin attachment; and (3) the pinned back attachment. Each attachment prototype was subjected to two vertical and two lateral dynamic component tests to evaluate the release loads and fracture mechanisms of the brackets. Test results were compared to previous tests on the bolted tabbed bracket (V10). None of the three bracket attachment designs were found to satisfy all of the design criteria for an alternative bracket. The lack of fixity in the connection between the brackets and the post led to a variable position of the tabs within the keyway which frequently caused unsatisfactory release loads. Therefore, none of the three alternative attachment brackets were recommended for use within the prototype non-proprietary cable barrier

A bilingual, Internet-based, targeted advertising campaign for prostate cancer clinical trials: Assessing the feasibility, acceptability, and efficacy of a novel recruitment strategy

Background: To address limitations in recruitment and enrollment of diverse, low-literacy patients into prostate cancer clinical trials, we evaluated the feasibility, acceptability, and efficacy of an English and Spanish, Internet-based, multilevel recruitment intervention. Methods: Intervention components included (1) a low-literacy, bilingual, automated, Internet-based clinical trial matching tool; (2) a bilingual nurse who assisted individuals with questions and enrollment; and (3) a targeted, Internet-based advertising campaign. We evaluated (a) completion of matching tool, (b) expression of interest in a clinical trial, (c) number of patients who matched to clinical trials at a single institution, (d) discussion of risks and benefits of clinical trials (via follow-up interviews), and (e) effect of the advertising on completing the matching tool. Feasibility, acceptability, and preliminary estimates of efficacy were measured through user engagement with the matching tool and subsequent qualitative interviews with these same users. Results: During the 28-week study period, 523 users provided demographic information, 263 were identified with prostate cancer, 192 (73%) matched to at least one clinical trial, and 29 (15.1%) of those who matched provided contact information. During the study period, 17 prostate cancer clinical trials were available for matching. We completed follow-up interviews with 14 of the 29 men who provided contact information. Of the 14, 85.7% discussed the risks and benefits of clinical trials with their physician, and 35.7% enrolled in a clinical trial. The Internet-based advertising campaign resulted in an increased number of matching tool completions. Conclusions: Our study demonstrates that an Internet-based clinical trial matching tool that is advertised using a targeted Internet-based campaign can provide an effective means to reach diverse, low-literacy patients. When implemented at scale and over a longer duration, such interventions may help increase trial participation among underrepresented populations. Keywords: Internet recruitment, Clinical trials participation, Prostate cancer, Underserved population

A bilingual, Internet-based, targeted advertising campaign for prostate cancer clinical trials: Assessing the feasibility, acceptability, and efficacy of a novel recruitment strategy.

BackgroundTo address limitations in recruitment and enrollment of diverse, low-literacy patients into prostate cancer clinical trials, we evaluated the feasibility, acceptability, and efficacy of an English and Spanish, Internet-based, multilevel recruitment intervention.MethodsIntervention components included (1) a low-literacy, bilingual, automated, Internet-based clinical trial matching tool; (2) a bilingual nurse who assisted individuals with questions and enrollment; and (3) a targeted, Internet-based advertising campaign. We evaluated (a) completion of matching tool, (b) expression of interest in a clinical trial, (c) number of patients who matched to clinical trials at a single institution, (d) discussion of risks and benefits of clinical trials (via follow-up interviews), and (e) effect of the advertising on completing the matching tool. Feasibility, acceptability, and preliminary estimates of efficacy were measured through user engagement with the matching tool and subsequent qualitative interviews with these same users.ResultsDuring the 28-week study period, 523 users provided demographic information, 263 were identified with prostate cancer, 192 (73%) matched to at least one clinical trial, and 29 (15.1%) of those who matched provided contact information. During the study period, 17 prostate cancer clinical trials were available for matching. We completed follow-up interviews with 14 of the 29 men who provided contact information. Of the 14, 85.7% discussed the risks and benefits of clinical trials with their physician, and 35.7% enrolled in a clinical trial. The Internet-based advertising campaign resulted in an increased number of matching tool completions.ConclusionsOur study demonstrates that an Internet-based clinical trial matching tool that is advertised using a targeted Internet-based campaign can provide an effective means to reach diverse, low-literacy patients. When implemented at scale and over a longer duration, such interventions may help increase trial participation among underrepresented populations