The need to recognise and account for the influence of working from home on commuting activity has never been so real as a result of the COVID-19 pandemic. Given a recognition that WFH activity ...during the pandemic has reduced the amount of commuting activity compared to pre-COVID-19, the inevitable question is raised as to what this might mean for some of the crucial inputs in the appraisal of transport initiatives. One critical value used in benefit-cost analysis is the value of time which converts time into monetary units in the calculation of user benefits. We are interested in whether reduced commuting activity is associated with higher or lower willing to pay to save time. We investigate this possibility with data from the Greater Sydney Metropolitan Area in late 2020 when working from home was at a high level. The findings of a higher average commuter VoT have major implications for the VoT used in transport appraisal given that time savings are the largest user benefit. We suggest a percentage adjustment required to align with the ‘new normal’ as currently known.
Aberrant accumulation of misfolded Cu, Zn superoxide dismutase (SOD1) is a hallmark of SOD1-associated amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disease. While recent ...discovery of nonnative trimeric SOD1-associated neurotoxicity has suggested a potential pathway for motor neuron impairment, it is yet unknown whether large, insoluble aggregates are cytotoxic. Here we designed SOD1 mutations that specifically stabilize either the fibrillar form or the trimeric state of SOD1. The designed mutants display elevated populations of fibrils or trimers correspondingly, as demonstrated by gel filtration chromatography and electron microscopy. The trimer-stabilizing mutant, G147P, promoted cell death, even more potently in comparison with the aggressive ALS-associated mutants A4V and G93A. In contrast, the fibril-stabilizing mutants, N53I and D101I, positively impacted the survival of motor neuron-like cells. Hence, we conclude the SOD1 oligomer and not the mature form of aggregated fibril is critical for the neurotoxic effects in the model of ALS. The formation of large aggregates is in competition with trimer formation, suggesting that aggregation may be a protective mechanism against formation of toxic oligomeric intermediates.
While there is a well-developed body of academic literature on how to procure public ground transport services and how to integrate those services, there is virtually no literature on how to do this ...in the context of regional air services. This paper aims to contribute to the area of strategic management of integrated transport based on the concept of mobility as a service. We show that customer-centric public transport integration (e.g. joint ticketing) with aviation as the highest priority can create business opportunities and competitive advantage for the ‘air-bus’ transport value chain. In the regional aviation context in particular, the door-to-door travel experience is of high importance given the potential competition from private car travel, except for island air services. Based on demand analysis and travel choice literature, we reveal that integrated planning and management efforts such as joint timetabling and joint pricing are most likely to have an impact on competitive advantage, demand (passenger numbers plus yields, measured in the customers’ willingness to pay) and hence the attractiveness and profitability of regional air services. We use stated choice experiments for flights from Sydney to regional New South Wales (NSW), Australia to establish the willingness to pay for integrated ground transport add-ons to scheduled regional air services.
Background
Condylar hyperplasia (CH) is a rare condition characterised by excessive unilateral growth of the mandibular condyle after cessation of growth on the contralateral side causing facial ...asymmetry, being more prevalent in the second and third decades.
Objective
The aim of this study was to determine the utility of vascular endothelial growth factor (VEGF‐A) as a diagnostic and prognostic factor in condylar hyperplasia, and to determine its potential viability as a therapeutic target.
Methods
This is a case–control study, where 17 mandibular condyles specimens were collected from 17 patients treated for active mandibular condyle hyperplasia and three unaffected human mandibular condyles from cadavers will serve as the control group. The samples were immunostained with VEGF‐A antibody and evaluated on both quantity and intensity of staining.
Results
VEGF‐A was qualitatively found to be greatly upregulated in patients with condylar hyperplasia.
Conclusion
VEGF‐A was qualitatively found to be upregulated in patients affected by CH, validating VEGF‐A as a potential diagnostic, prognostic and therapeutic target.
The presence of DAB staining, which only occurs within the chondrocytes of cartilaginous tissues, was used to establish the presence of VEGF‐A. When background staining was seen, it was infrequent and isolated to the lacunae and the chondrocytes that lived there. All CH samples showed this similar pattern of intense staining (Figure 1).
•The hypothetical nature of stated preference experiments can create biased results.•Mitigation is attempted by calibrating models based on the certainty of choice being made.•Unique stated and ...revealed preference experiment is used to assess mitigation.•Incorrect use of certainty calibration can induce greater levels of bias.•Jointly estimating choice and choice certainty significantly reduces hypothetical bias.
Stated choice experiments are a preeminent method for researchers and practitioners who seek to examine the behavior of consumers. However, the extent to which these experiments can replicate real markets continues to be debated in the literature, with particular reference to the potential for biased estimates as a result of the hypothetical nature of such experiments. In this paper, a first in the transportation literature, we compare stated choice responses to revealed preference behavior and examine three methods proposed in the literature for calibrating choice experiments via reported choice certainty. In doing so we provide evidence that the incorrect calibration of responses can produce stated choice results that are more biased than doing nothing at all, however we show that by jointly estimating choice and choice certainty there is a significant reduction in hypothetical bias such that stated choice responses more directly replicate real behavior.
ABSTRACT
Auditor credibility is important in the banking industry due to the opacity of bank assets and the use of financial statements by external parties to facilitate monitoring. Depositors ...monitor and discipline bank behavior, but they can also contribute to the spread of shocks from one bank to another. We argue that depositors perceive bank failure as an audit failure, which reduces their assessment of auditor credibility. We document that exposure to failure through the audit firm is associated with lower uninsured deposit growth following the failure, consistent with depositors perceiving failures as a negative signal of auditor credibility. We further document that this association is stronger when depositors perceive connection to failure to reflect a pervasive issue within the audit firm. Collectively, our results suggest that depositors consider accounting signals at other banks in assessing financial reporting credibility.
JEL Classifications: G21; M41; M42.
Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 ...family to be strikingly induced during the late stages of brain maturation. Brain maturation is associated with a transient, postnatal period of de novo non-CG (CH) DNA methylation mediated by DNMT3A. We examine whether an important function of miR-29 during brain maturation is to restrict the period of CH methylation via its targeting of Dnmt3a. Deletion of miR-29 in the brain, or knockin mutations preventing miR-29 to specifically target Dnmt3a, result in increased DNMT3A expression, higher CH methylation, and repression of genes associated with neuronal activity and neuropsychiatric disorders. These mouse models also develop neurological deficits and premature lethality. Our results identify an essential role for miR-29 in restricting CH methylation in the brain and illustrate the importance of CH methylation regulation for normal brain maturation.
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•miR-29 is markedly upregulated during postnatal brain maturation•miR-29 targets Dnmt3a to restrict its expression in vivo in the maturing brain•miR-29 regulates Dnmt3a and mCH to control the expression of synaptic genes•Failure of miR-29 to restrict Dnmt3a leads to neurobehavioral deficits
Non-canonical CH methylation mediated by DNMT3A during neuronal maturation has been recently shown to be critical for brain homeostasis. Swahari et al. identify a key player that is critical for regulating CH methylation: the microRNA miR-29. Failure of miR-29 to regulate the expression of Dnmt3a leads to severe neurobehavioral consequences.
The purpose of this study was to provide insight to the lived advocacy experiences of principals and school counselors who received state and/or national recognition for their work on behalf of ...lesbian, gay, bisexual, and transgender (LGBT) students. I identified three themes and related subthemes regarding the meaning derived across the participants' advocacy experiences on behalf of LGBT students. The first theme was "It began with me" with subtheme (a) knowing your school. The second theme was advocacy identity with subthemes (a) being a role model, and (b) taking a stand. The third theme was credibility and confidence with subtheme (a) giving back. These findings provide school counselors and principals with stories and practical examples from exemplary and dedicated professionals regarding how to create safer school environments for LGBT students.
Prior research emphasizes the centrality of audit offices in understanding auditing practices, and documents significant interoffice variation in audit outcomes based on industry expertise and office ...size. Our study examines how two city‐specific labor characteristics also affect audit offices and local audit markets: the city's average educational attainment, and the number of accountants in a city, which proxy for a city's human capital. Our argument draws on the urban economics literature and predicts that the level of human capital in a city is positively associated with an audit office's ability to conduct high‐quality audits. As expected, there is a positive association between audit quality (quality of audited earnings and accuracy of going‐concern reports) and average education level in the city in which the lead engagement office is located. This association is generally significant for both Big 4 and non‐Big 4 offices, but is relatively stronger for non‐Big 4 firms that are more tied to local labor markets. A company is also more likely to choose a non‐Big 4 auditor in cities with higher educational levels and relatively more accountants, and there is evidence of higher non‐Big 4 audit fees as a city's education level increases. Collectively, these results suggest that local labor characteristics affect audit offices, audit quality, and the ability of non‐Big 4 auditors to compete with Big 4 auditors in the audits of public companies.
Audits des sociétés cotées et caractéristiques de la main‐d’œuvre propres à la ville
Les études antérieures sont axées sur la centralité des bureaux d'audit dans la compréhension des méthodes d'audit et font état, preuves à l'appui, de variations importantes des résultats de l'audit entre les bureaux, selon les compétences sectorielles et la taille des bureaux. Les auteurs se penchent ici sur la façon dont deux caractéristiques de la main‐d’œuvre propres à la ville influent également sur les bureaux d'audit et les marchés d'audit régionaux : le niveau de scolarité moyen et l'effectif comptable de la ville, indicateurs servant de variables de substitution au capital humain de la ville. Les auteurs fondent leur argumentation sur la documentation en économie urbaine et posent l'hypothèse selon laquelle le niveau de capital humain d'une ville serait en relation positive avec la capacité d'un bureau d'audit de mener des audits de qualité supérieure. Leur analyse confirme l'existence d'un lien positif entre la qualité de l'audit (qualité des résultats audités et exactitude des rapports sur la continuité de l'exploitation) et le niveau de scolarité moyen de la ville où se trouve le bureau responsable de la mission. Ce lien est généralement significatif tant pour les bureaux des Quatre Grands cabinets que pour les bureaux des cabinets n'appartenant pas à ce groupe, mais il est relativement plus marqué dans le cas des cabinets ne faisant pas partie des Quatre Grands qui sont liés de plus près aux marchés du travail régionaux. Une société est également davantage susceptible de choisir un auditeur n'appartenant pas aux Quatre Grands dans les villes où le niveau de scolarité est plus élevé et où l'effectif comptable est relativement plus grand, et certaines données révèlent que les honoraires d'audit des cabinets n'appartenant pas aux Quatre Grands augmentent avec la hausse du niveau de scolarité d'une ville. Dans leur ensemble, ces résultats semblent indiquer que les caractéristiques de la main‐d’œuvre régionale influent sur les bureaux d'audit, sur la qualité de l'audit et sur la capacité des auditeurs n'appartenant pas aux Quatre Grands de rivaliser avec les auditeurs des Quatre Grands dans les audits des sociétés cotées.
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