Low-Stress Bicycling and Network Connectivity

For a bicycling network to attract the widest possible segment of the population, its most fundamental attribute should be low-stress connectivity, that is, providing routes between people’s origins and destinations that do not require cyclists to use links that exceed their tolerance for traffic stress, and that do not involve an undue level of detour. The objective of this study is to develop measures of low-stress connectivity that can be used to evaluate and guide bicycle network planning. We propose a set of criteria by which road segments can be classified into four levels of traffic stress (LTS). LTS 1 is suitable for children; LTS 2, based on Dutch bikeway design criteria, represents the traffic stress that most adults will tolerate; LTS 3 and 4 represent greater levels of stress. As a case study, every street in San Jose, California, was classified by LTS. Maps in which only bicycle-friendly links are displayed reveal a city divided into islands within which low-stress bicycling is possible, but separated from one another by barriers that can be crossed only by using high-stress links. Two points in the network are said to be connected at a given level of traffic stress if the subnetwork of links that do not exceed the specified level of stress connects them with a path whose length does not exceed a detour criterion (25% longer than the most direct path). For the network as a whole, we demonstrate two measures of connectivity that can be applied for a given level of traffic stress. One is “percent trips connected,” defined as the fraction of trips in the regional trip table that can be made without exceeding a specified level of stress and without excessive detour. This study used the home-to-work trip table, though in principle any trip table, including all trips, could be used. The second is “percent nodes connected,” a cruder measure that does not require a regional trip table, but measures the fraction of nodes in the street network (mostly street intersections) that are connected to each other. Because traffic analysis zones (TAZs) are too coarse a geographic unit for evaluating connectivity by bicycle, we also demonstrate a method of disaggregating the trip table from the TAZ level to census blocks. For any given TAZ, origins in the home-to-work trip table are allocated in proportion to population, while destinations are allocated based on land-use data. In the base case, the fraction of work trips up to six miles long that are connected at LTS 2 is 4.7%, providing a plausible explanation for the city’s low bicycling share. We show that this figure would almost triple if a proposed slate of improvements, totaling 32 miles in length but with strategically placed segments that provide low-stress connectivity across barriers, were implemented

Self-Organizing Signals: A Better Framework for Transit Signal Priority

Actuated traffic signal control logic has many advantages because of its responsiveness to traffic demands, short cycles, effective use of capacity leading to and recovering from oversaturation, and amenability to aggressive transit priority. Its main drawback has been its inability to provide good progression along arterials. However, the traditional way of providing progression along arterials, coordinated-actuated control with a common, fixed cycle length, has many drawbacks stemming from its long cycle lengths, inflexibility in recovering from priority interruptions, and ineffective use of capacity during periods of oversaturation. This research explores a new paradigm for traffic signal control, “self-organizing signals,” based on local actuated control but with some additional rules that create coordination mechanisms. The primary new rules proposed are for secondary extensions, in which the green may be held to serve an imminently arriving platoon, and dynamic coordination, in which small groups of closely spaced signals communicate with one another to cycle synchronously with the group’s critical intersection. Simulation tests in VISSIM performed on arterial corridors in Massachusetts and Arizona show overall delay reductions of up to 14% compared to an optimized coordinated-actuated scheme where there is no transit priority, and more than 30% in scenarios with temporary oversaturation. Tests also show that with self-organizing control, transit signal priority can be more effective than with coordinated-actuated control, reducing transit delay by about 60%, or 12 to 14 s per intersection with little impact on traffic delay.https://pdxscholar.library.pdx.edu/trec_seminar/1054/thumbnail.jp

Measuring low-stress connectivity in terms of bike-accessible jobs and potential bike-to-work trips: A case study evaluating alternative bike route alignments in northern Delaware

When road segments with high traffic stress are excluded, the remaining network of low-stress roads and trails can be fragmented, lacking connections between many origin-destination pairs or requiring onerous detour. Low-stress connectivity is a measure of the degree to which origins (for this study, homes) and destinations (jobs) can be connected using only low-stress links and without excessive detour. Revision 2.0 to Level of Traffic Stress criteria is introduced and applied to the road and trail network of northern Delaware. A propensity model is proposed to reflect people’s declining willingness to ride a bike with greater trip length and detour, accounting for the impact to health and other benefits of cycling. New connectivity measures are introduced that can be interpreted as the number of bike-accessible jobs and the potential number of bike-to-work trips, powerful measures for evaluating alternatives. These connectivity measures are applied in a case study evaluating alternative alignments for a bike route between Wilmington and Newark, Delaware’s two largest cities, separated by a distance of about 20 km through a largely suburban landscape. The case study explores the benefits of enhancing alternatives with branches that help connect to population and employment centers. We also find that the connectivity gain from constructing multiple alignments is greater than the sum of connectivity gains from individual alignments, indicating that complementarity between the alternatives, which are spaced roughly 5 km apart, overshadows any competition between them

Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury

Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions and potential repairing therapies. Experimental machine perfusion using porcine kidneys is a great way to investigate transplant-related IRI, but these experiments are costly and time-consuming. Therefore, an intermediate model to study IRI would be of great value. We developed a precision-cut kidney slice (PCKS) model that resembles ischemia-reperfusion and provides opportunities for studying multiple interventions simultaneously. Porcine kidneys were procured from a local slaughterhouse, exposed to 30 min of warm ischemia, and cold preserved. Subsequently, PCKS were prepared and incubated under various conditions. Adenosine triphosphate (ATP) levels and histological tissue integrity were assessed for renal viability and injury. Slicing did not influence tissue viability, and PCKS remained viable up to 72 h incubation with significantly increased ATP levels. Hypothermic and normothermic incubation led to significantly higher ATP levels than baseline. William’s medium E supplemented with Ciprofloxacin (and Amphotericin-B) provided the most beneficial condition for incubation of porcine PCKS. The porcine PCKS model can be used for studying transplant IR

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202