Toll-managed lane pioneers: Lessons from five US states

Toll-managed lanes have become an increasingly popular technique among transportation policymakers for managing congestion on existing highways and, in some cases, financing the construction of new lanes in congested urban corridors. Although growing in popularity, the adoption of these facilities is concentrated in five states: Texas, California, Colorado, Minnesota, and Florida. This paper examines the adoption and utilization of toll-managed lanes in these pioneer states. Using archival, case-based research, our analysis suggests that the adoption of toll-managed lanes was driven by a combination of factors, including rapid population growth, near or above average growth in vehicle miles traveled (VMT), and insufficient gas tax funding for transportation investments. Implementation was also generally similar across states but some of the pioneers delegated the management of their toll-managed lane programs to special regional highway authorities while others used state highway agencies

Toll-Managed Lanes: Benefit-Cost Analyses of Seven Projects. Year 25 Final Report

Toll managed lanes are expressway lanes where tolls are used--often in combination with preferred access for high occupancy vehicles and other special traffic management techniques-- to improve the highway’s capacity, speed or reliability. Such lanes, and particularly a variant called High Occupancy Toll (HOT) lanes, have become popular with transportation policymakers as a way of maintaining free-flowing traffic on existing lanes while also, in some cases, financing the construction of new lanes in congested urban areas. This study examines whether toll-managed lanes are as beneficial as they are popular. The heart of the analysis is the application of a simplified social benefit-cost analysis to seven projects. In brief, the results suggest that toll-managed lanes, while promising, are not a surefire strategy for managing congestion. Only two of the seven projects have benefit-cost ratios above 1.0 using our base case assumptions about the value of travel time saved and the discount rate, although three others approach or exceed 1.0 with more optimistic but plausible assumptions. The most successful generate not only a significant savings of around 4 to 5 minutes per trip for motorists who switch to the managed lane but also smaller per-trip savings for the large majority of motorists who continue to use the general-purpose lanes. It is important to acknowledge, however, that these calculations depend upon some uncertain assumptions about the value of travel time savings and improved reliability

Investigation of gene-environment interactions in relation to tic severity

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies

Molecular mechanisms of vaspin action: from adipose tissue to skin and bone, from blood vessels to the brain

Visceral adipose tissue derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that  were specifically expressed or overexpressed in the intra abdominal or visceral adipose tissue  (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral  obesity, insulin resistance, hyperinsulinemia and ‐glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type  2 diabetes.  The follow-up study reporting the cloning, expression and functional characterization of  vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs. This review will give an update on mechanistic and structural aspects of vaspin with a focus on its serpin function, the physiology and regulation of vaspin expression, and will summarize the latest on vaspin function in various tissues such as the different adipose tissue depots as well as the vasculature, skin, bone and the brain

Adopting a high-polyphenolic diet is associated with an improved glucose profile: prospective analysis within the PREDIMED-plus trial

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks

Background For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). Objective To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). Methods Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). Results A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. Conclusions In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations