Accounting for Endogeneity in Maintenance Decisions and Overlay Thickness in a Pavement-Roughness Deterioration Model

Pavement deterioration models are an important part of any pavement management system. Many of these models suffer from endogeneity bias because of the inclusion of independent variables correlated with unobserved factors, which are captured by the model's error terms. Examples of such endogenous variables include pavement overlay thickness and maintenance and rehabilitation activities, both of which are not randomly chosen but are in fact decision variables selected by pavement engineers based on field conditions. Inclusion of these variables in a pavement deterioration model can result in biased and inconsistent model parameter estimates, leading to incorrect insights. Previous research has shown that continuous endogenous variables, such as pavement overlay thickness, can be corrected using auxiliary models to replace the endogenous variable with an instrumented variable that has lower correlation with the unobserved error term. Discrete endogenous variables, such as the type of maintenance and rehabilitation activities, have been accounted for by modeling the likelihood of each potential outcome and developing individual deterioration models for each of the potential responses. This paper proposes an alternative approach to accommodate discrete endogenous variables-the selectivity correction method-that allows a single model to incorporate the impacts of all discrete choices. This approach is applied to develop a pavement-roughness progression model that incorporates both continuous and discrete endogenous variables using field data from Washington State. The result is a roughness progression model with consistent parameter estimates, which have more realistic values than those obtained in previous studies that used the same data

HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells

Seasonal influenza virus infections cause 290,000–650,000 deaths annually and severe morbidity in 3–5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases

Simultaneous equation penalized likelihood estimation of vehicle accident injury severity

A bivariate system of equations is developed to model ordinal polychotomous dependent variables within a simultaneous additive regression framework. The functional form of the covariate effects is assumed fairly flexible with appropriate smoothers used to account for non‐linearities and spatial variability in the data. Non‐Gaussian error dependence structures are dealt with by means of copulas whose association parameter is also specified in terms of a generic additive predictor. The framework is employed to study the effects of several risk factors on the levels of injury sustained by individuals in two‐vehicle accidents in France. The use of the methodology proposed is motivated by the presence of common unobservables that may affect the interrelationships between the parties involved in the same crash and by the possible heterogeneity in individuals’ characteristics and accident dynamics. Better calibrated estimates are obtained and misspecification reduced via an enhanced model specification

T Cells Recognizing a Peptide Contaminant Undetectable by Mass Spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP206-214 using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP206-214. If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results

Modeling offenses among motorcyclists involved in crashes in Spain

In relative terms, Spanish motorcyclists are more likely to be involved in crashes than other drivers and this tendency is constantly increasing. The objective of this study is to identify the factors that are related to being an offender in motorcycle accidents. A binary logit model is used to differentiate between offender and non-offender motorcyclists. A motorcyclist was considered to be offender when she had committed at least one traffic offense at the moment previous to the crash. The analysis is based on the official accident database of the Spanish general directorate of traffic (DGT) for the 2003-2008 time period. A number of explanatory variables including motorcyclist characteristics and environmental factors have been evaluated. The results suggest that inexperienced, older females, not using helmets, absent-minded and non-fatigued riders are more likely to be offenders. Moreover, riding during the night, on weekends, for leisure purposes and along roads in perfect condition, mainly on curves, predict offenses among motorcyclists. The findings of this study are expected to be useful in developing traffic policy decisions in order to improve motorcyclist safety

Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

BACKGROUND: Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. METHODS: The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. RESULTS: Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). CONCLUSIONS: The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models

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Assessing the importance of car meanings and attitudes in consumer evaluations of electric vehicles

This paper reports findings from a research study which assesses the importance of attitudinal constructs related to general car attitudes and the meanings attached to car ownership over evaluations of electric vehicles (EVs). The data are assessed using principal component analysis to evaluate the structure of the underlying attitudinal constructs. The identified constructs are then entered into a hierarchical regression analysis which uses either positive or negative evaluations of the instrumental capabilities of EVs as the dependent variable. Results show that attitudinal constructs offer additional predictive power over socioeconomic characteristics and that the symbolic and emotive meanings of car ownership are as, if not more, effective in explaining the assessment of EV instrumental capability as compared to issues of cost and environmental concern. Additionally, the more important an individual considers their car to be in their everyday life, the more negative their evaluations are of EVs whilst individuals who claim to be knowledgeable about cars in general and EVs in particular have a lower propensity for negative EV attitudes. However, positive and negative EV attitudes are related to different attitudinal constructs suggesting that it is possible for someone to hold both negative and positive assessments at the same time