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Background: Pressure is growing in North America for heavy-duty, long-haul trucking to reduce greenhouse gas (GHG) emissions, ultimately to zero. With freight volumes rising, improvement depends on zero-emissions technologies, e.g., battery electric vehicles (BEVs) and fuel cell electric vehicles (FCEVs). However, emissions reductions are constrained by technological and commercial realities. BEVs and FCEVs are expensive. Further, BEVs depend on existing electricity grids and FCEVs rely on steam–methane reforming (SMR) or electrolysis using existing grids to produce hydrogen. Methods: This study assembles publicly available data from reputable sources to estimate breakeven vehicle purchase prices under various conditions to match conventional (diesel) truck prices. It also estimates GHG emissions reductions. Results: BEVs face numerous obstacles, including (1) limited range; (2) heavy batteries and reduced cargo capacity; (3) long recharging time; and (4) uncertain hours-of-service (HOS) implications. On the other hand, FCEVs face two primary obstacles: (1) cost and availability of hydrogen and (2) cost of fuel cells. Conclusions: In estimating emissions reductions and economic feasibility of BEVs and FCEVs versus diesel trucks, the primary contributions of this study involve its consideration of vehicle prices, carbon taxes, and electricity grid capacity constraints and demand fees. As electricity grids reduce their emissions intensity, grid congestion and capacity constraints, opportunities arise for BEVs. On the other hand, rising electricity demand fees benefit FCEVs, with SMR-produced hydrogen a logical starting point. Further, carbon taxation appears to be less important than other factors in the transition to zero-emission trucking. [ABSTRACT FROM AUTHOR]

Background: Pressure is growing in North America for heavy-duty, long-haul trucking to reduce greenhouse gas (GHG) emissions, ultimately to zero. With freight volumes rising, improvement depends on zero-emissions technologies, e.g., battery electric vehicles (BEVs) and fuel cell electric vehicles (FCEVs). However, emissions reductions are constrained by technological and commercial realities. BEVs and FCEVs are expensive. Further, BEVs depend on existing electricity grids and FCEVs rely on steam–methane reforming (SMR) or electrolysis using existing grids to produce hydrogen. Methods: This study assembles publicly available data from reputable sources to estimate breakeven vehicle purchase prices under various conditions to match conventional (diesel) truck prices. It also estimates GHG emissions reductions. Results: BEVs face numerous obstacles, including (1) limited range; (2) heavy batteries and reduced cargo capacity; (3) long recharging time; and (4) uncertain hours-of-service (HOS) implications. On the other hand, FCEVs face two primary obstacles: (1) cost and availability of hydrogen and (2) cost of fuel cells. Conclusions: In estimating emissions reductions and economic feasibility of BEVs and FCEVs versus diesel trucks, the primary contributions of this study involve its consideration of vehicle prices, carbon taxes, and electricity grid capacity constraints and demand fees. As electricity grids reduce their emissions intensity, grid congestion and capacity constraints, opportunities arise for BEVs. On the other hand, rising electricity demand fees benefit FCEVs, with SMR-produced hydrogen a logical starting point. Further, carbon taxation appears to be less important than other factors in the transition to zero-emission trucking.

Aims/hypothesisOxylipins are lipid mediators derived from polyunsaturated fatty acids. Some oxylipins are proinflammatory (e.g. those derived from arachidonic acid [ARA]), others are pro-resolving of inflammation (e.g. those derived from α-linolenic acid [ALA], docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) and others may be both (e.g. those derived from linoleic acid [LA]). The goal of this study was to examine whether oxylipins are associated with incident type 1 diabetes.MethodsWe conducted a nested case-control analysis in the Diabetes Autoimmunity Study in the Young (DAISY), a prospective cohort study of children at risk of type 1 diabetes. Plasma levels of 14 ARA-derived oxylipins, ten LA-derived oxylipins, six ALA-derived oxylipins, four DHA-derived oxylipins and two EPA-related oxylipins were measured by ultra-HPLC-MS/MS at multiple timepoints related to autoantibody seroconversion in 72 type 1 diabetes cases and 71 control participants, which were frequency matched on age at autoantibody seroconversion (of the case), ethnicity and sample availability. Linear mixed models were used to obtain an age-adjusted mean of each oxylipin prior to type 1 diabetes. Age-adjusted mean oxylipins were tested for association with type 1 diabetes using logistic regression, adjusting for the high risk HLA genotype HLA-DR3/4,DQB1*0302. We also performed principal component analysis of the oxylipins and tested principal components (PCs) for association with type 1 diabetes. Finally, to investigate potential critical timepoints, we examined the association of oxylipins measured before and after autoantibody seroconversion (of the cases) using PCs of the oxylipins at those visits.ResultsThe ARA-related oxylipin 5-HETE was associated with increased type 1 diabetes risk. Five LA-related oxylipins, two ALA-related oxylipins and one DHA-related oxylipin were associated with decreased type 1 diabetes risk. A profile of elevated LA- and ALA-related oxylipins (PC1) was associated with decreased type 1 diabetes risk (OR 0.61; 95% CI 0.40, 0.94). A profile of elevated ARA-related oxylipins (PC2) was associated with increased diabetes risk (OR 1.53; 95% CI 1.03, 2.29). A critical timepoint analysis showed type 1 diabetes was associated with a high ARA-related oxylipin profile at post-autoantibody-seroconversion but not pre-seroconversion.Conclusions/interpretationThe protective association of higher LA- and ALA-related oxylipins demonstrates the importance of both inflammation promotion and resolution in type 1 diabetes. Proinflammatory ARA-related oxylipins may play an important role once the autoimmune process has begun.

BackgroundDNA methylation studies in Parkinson's disease (PD) thus far have focused on disease susceptibility but not progression.ObjectiveIn this epigenome-wide association study (EWAS), we aim to identify methylation markers associated with faster cognitive decline or motor progression in PD.MethodsWe included 232 PD patients from the Parkinson's Environment and Gene follow-up study who provided blood samples at enrolment. Information on cognitive and motor function was collected using the Mini-Mental State Examination (MMSE) and Unified Parkinson's Disease Rating Scale (UPDRS). For EWAS analyses, we used a robust measure of correlation: biweight midcorrelations, t-tests, and Cox proportional hazard models. We also conducted weighted correlation network analysis (WGCNA) to identify CpG modules associated with cognitive decline or motor progression in PD.ResultsAmong 197 individuals of European ancestry, with our EWAS approach we identified 7 genome-wide significant CpGs associated with a MMSE 4-point decline and 8 CpGs associated with faster motor progression (i.e., rate of UPDRS increase ≥5-point/year). The most interesting CpGs for cognitive decline include cg17445913 in KCNB1 (cor = 0.36, p = 6.85×10-7) and cg02920897 in DLEU2 (cor = 0.34, p = 3.23×10-6), while for motor progression it was cg01754178 in PTPRN2 (cor = - 0.34, p = 2.07×10-6). In WGCNA, motor progression related modules were enriched for genes related to neuronal synaptic functions, Wnt signaling pathway, and mitochondrial apoptosis.ConclusionsOur study provides the first epigenetic evidence that differential methylation in genes previously identified as being associated with cognitive impairment, neuronal synaptic function, Wnt signaling pathway, and mitochondrial apoptosis is associated with cognitive and motor progression in PD.

The contributions of coding mutations to tumorigenesis are relatively well known; however, little is known about somatic alterations in noncoding DNA. Here we describe GECCO (Genomic Enrichment Computational Clustering Operation) to analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas (PDAs) and identify commonly mutated regulatory regions. We find recurrent noncoding mutations to be enriched in PDA pathways, including axon guidance and cell adhesion, and newly identified processes, including transcription and homeobox genes. We identified mutations in protein binding sites correlating with differential expression of proximal genes and experimentally validated effects of mutations on expression. We developed an expression modulation score that quantifies the strength of gene regulation imposed by each class of regulatory elements, and found the strongest elements were most frequently mutated, suggesting a selective advantage. Our detailed single-cancer analysis of noncoding alterations identifies regulatory mutations as candidates for diagnostic and prognostic markers, and suggests new mechanisms for tumor evolution.

ObjectiveTo evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH: is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score