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Argininosuccinate lyase (ASL) is a key enzyme integral to the hepatic urea cycle which is required for ammonia detoxification, and the citrulline-nitric oxide (NO) cycle for NO production. ASL deficient patients present with argininosuccinic aciduria (ASA), an inherited metabolic disease with hyperammonaemia and a chronic systemic phenotype with neurocognitive impairment and chronic liver disease. ASL deficiency as an inherited model of systemic NO deficiency, shows enhanced nitrosative and oxidative stress. Here, we describe the dysregulation of glutathione biosynthesis and upstream cysteine utilization in ASL-deficient patients and mice using targeted metabolomics andin vivopositron emission tomography (PET) imaging using (S)-4-(3-18F-fluoropropyl)-L-glutamate ([18F]FSPG). Upregulation of cysteine metabolism contrasted with glutathione depletion and down-regulated antioxidant pathways.hASLmRNA encapsulated in lipid nanoparticles corrected and rescued the neonatal and adult Asl-deficient mouse phenotypes, respectively, enhancing ureagenesis and glutathione metabolism and ameliorating chronic liver disease. We further present [18F]FSPG PET as a novel non-invasive diagnostic tool to assess liver disease and therapeutic efficacy in ASA. These findings support clinical translation of mRNA therapy for ASA.

Using a uniquely hand-collected dataset, we examine how financial analysts react to expectations management in the post-Regulation Fair Disclosure (FD) period. We find evidence that management issues pessimistic public guidance to lower analysts’ expectations to a beatable level in the new regulatory environment. Majority of the analysts revised their forecasts downward immediately (in terms of days rather than weeks) after the issuance of a pessimistic public guidance. The magnitude of the downward revision is significantly greater for firms that beat the expectations through managerial guidance than firms that beat the expectations without guidance. In addition, firms that beat analysts’ expectations through pessimistic guidance are able to achieve a larger positive earnings surprise at the earnings announcement than the legitimate beaters.

The purpose was to determine differences by gender and over time in use of coping strategies by students following the 2008 mass shootings at Northern Illinois University. Students (N=336) complete...

PurposePrevious research has provided mixed evidence on the relative importance of three earnings thresholds that managers seek to achieve: avoiding losses, avoiding earnings declines and avoiding negative earnings surprises. The purpose of this paper is to investigate whether firm‐specific factors influence management's preferences for an earnings threshold.Design/methodology/approachLogit models are estimated to explore the relationships between firm‐characteristics and management's perceptions of the relative importance of each threshold.FindingsThis paper finds that: large firms, firms with high growth prospects and firms with high trading volume are more concerned with avoiding negative earnings surprises, while small firms, firms with low growth prospects and firms with low trading volume are more prone to avoid earnings declines and losses; for firms with high analyst forecast accuracy (relative to a random walk model forecast), avoiding negative earnings surprises is more important than avoiding earnings declines and losses; and firms with low analyst forecast dispersion focus more on avoiding negative earnings surprises and losses, while firms with high analyst forecast dispersion focus more on avoiding earnings declines. Overall, this paper shows that firm characteristics do affect management's perceptions of the relative importance of each threshold.Originality/valueThis study recognizes the cross‐sectional differences in the earnings threshold hierarchy. The results suggest that regulators and practitioners should focus on different thresholds for different types of firms when investigating the mechanisms used to achieve the thresholds.

To better understand and serve Asian-Americans, it is imperative for the family science related fields to take a leadership role in providing in-depth insight into Asian-American families. In this article we report a descriptive analysis of articles published in prominent family-based journals over a 14-year period (1992–2006) relative to their attention to Asian-American families. This study examines the types of research conducted and the knowledge that has been generated about Asian-American families. It also provides a framework for considering future culturally centered research with this population.

In this article, the authors draw from feminist, critical, and multicultural research traditions to identify fundamental assumptions for researching from a feminist-informed, critical, multicultural stance. Core considerations include amplifying marginalized voices, interrogating the politics of knowledge production, ensuring research benefits to those at the center of analysis, attending to culture and context, holding ourselves accountable as researchers for our own multicultural competence, and using diverse methodologies to support social equity. They offer examples of critical multicultural research and argue for the potential of this approach to contribute to a corrective research agenda in the field of family studies.