Regulation of Chemical Risks: Lessons for Reform of the Toxic Substances Control Act from Canada and the European Union

The purpose of this Article is to compare the regulatory systems in Canada and the EU, and use comparative insights to draw some lessons that may be of interest to U.S. policy makers engaged in TSCA reform. CEPA and REACH are seen by stakeholders as state of the art in chemicals assessment and management, and thus the U.S. may draw useful insights from them. Indeed, the European Union and Canada have each been urging other countries to join in a globalization of the REACH or Canadian programs, respectively. Regardless of what TSCA reformers choose to learn from the Canadian and European experiences, a secondary objective of the Article is to provide comparative information that may be of interest to reformers in Canada, Europe, or other countries and regions where chemical risk management is under consideration for reform. Thus, the Article\u27s long-term value extends beyond the current U.S. debate over TSCA reform. The Article is organized in three Parts. In Part I, we describe the scope of our analysis, our research methods, and our analytical approach. In Parts II and III, we compare CEPA and REACH across two significant dimensions: (1) prioritization of existing chemicals for assessment and regulation; and (2) placement of the burdens to produce data and demonstrate safety of specific chemical uses. We conclude by summarizing the possible lessons for TSCA reform and highlighting some future research needs

Exact Asymptotic Results for Persistence in the Sinai Model with Arbitrary Drift

We obtain exact asymptotic results for the disorder averaged persistence of a Brownian particle moving in a biased Sinai landscape. We employ a new method that maps the problem of computing the persistence to the problem of finding the energy spectrum of a single particle quantum Hamiltonian, which can be subsequently found. Our method allows us analytical access to arbitrary values of the drift (bias), thus going beyond the previous methods which provide results only in the limit of vanishing drift. We show that on varying the drift, the persistence displays a variety of rich asymptotic behaviors including, in particular, interesting qualitative changes at some special values of the drift.Comment: 17 pages, two eps figures (included

Geochemical analysis of bulk marine sediment by Inductively Coupled Plasma–Atomic Emission Spectroscopy on board the JOIDES Resolution

Geochemical analyses on board the JOIDES Resolution have been enhanced with the addition of a Jobin-Yvon Ultrace inductively coupled plasma-atomic emission spectrometer (ICP-AES) as an upgrade from the previous X-ray fluorescence facility. During Leg 199, we sought to both challenge and utilize the capabilities of the ICP-AES in order to provide an extensive bulk-sediment geochemical database during the cruise. These near real-time analyses were then used to help characterize the recovered sedimentary sequences, calculate mass accumulation rates of the different sedimentary components, and assist with cruise and postcruise sampling requests. The general procedures, sample preparation techniques, and basic protocol for ICP-AES analyses on board ship are outlined by Murray et al. (2000) in Ocean Drilling Program Tech Note, 29. We expand on those concepts and offer suggestions for ICP-AES methodology, calibration by standard reference materials, data reduction procedures, and challenges that are specific to the analysis of bulk-sediment samples. During Leg 199, we employed an extensive bulk-sediment analytical program of ~600 samples of varying lithologies, thereby providing several opportunities for refinement of techniques. We also discuss some difficulties and challenges that were faced and suggest how to alleviate such occurrences for sedimentary chemical analyses during future legs

Inhibiting efferocytosis reverses macrophage-mediated immunosuppression in the leukemia microenvironment

Background: Previous studies show that the spleen and bone marrow can serve as leukemia microenvironments in which macrophages play a significant role in immune evasion and chemoresistance. We hypothesized that the macrophage driven tolerogenic process of efferocytosis is a major contributor to the immunosuppressive leukemia microenvironment and that this was driven by aberrant phosphatidylserine expression from cell turnover and cell membrane dysregulation. Methods: Since MerTK is the prototypic efferocytosis receptor, we assessed whether the MerTK inhibitor MRX2843, which is currently in clinical trials, would reverse immune evasion and enhance immune-mediated clearance of leukemia cells. Results: We found that inhibition of MerTK decreased leukemia-associated macrophage expression of M2 markers PD-L1, PD-L2, Tim-3, CD163 and Arginase-1 compared to vehicle-treated controls. Additionally, MerTK inhibition led to M1 macrophage repolarization including elevated CD86 and HLA-DR expression, and increased production of T cell activating cytokines, including IFN-β, IL-18, and IL-1β through activation of NF-κB. Collectively, this macrophage repolarization had downstream effects on T cells within the leukemia microenvironment, including decreased PD-1+Tim-3+ and LAG3+ checkpoint expression, and increased CD69+CD107a+ expression. Discussion: These results demonstrate that MerTK inhibition using MRX2843 altered the leukemia microenvironment from tumor-permissive toward immune responsiveness to leukemia and culminated in improved immune-mediated clearance of AML

Of Research reviews and practice guides: Translating rapidly growing research on adolescent literacy into updated practice recommendations.

The demand for evidence-based instructional practices has driven a large supply of research on adolescent literacy. Documenting this supply, Baye, Inns, Lake, and Slavin’s 2019 article in Reading Research Quarterly synthesized far more studies, with far more rigorous methodology, than had ever been collected before. What does this mean for practice? Inspired by this article, I investigated how this synthesis compared with the 2008 U.S. Institute of Education Sciences practice guide for adolescent literacy. I also include two contemporary documents for context: Herrera, Truckenmiller, and Foorman’s (2016) review and the U.K. Education Endowment Foundation’s 2019 practice guide for secondary schools. I first examine how these documents define adolescent, reading, and evidence, and propose more inclusive definitions. I then compare their respective evidence bases, finding that the quality and quantity of evidence have dramatically changed. Only one of the 34 studies in the 2008 U.S. practice guide met Baye et al.’s inclusion criteria in 2019, and the average sample size in Baye et al.’s studies was 22 times as large as those in the 2008 U.S. practice guide. I also examine the potential implications for a new practice guide’s instructional recommendations and comment on the expansion of research in technology, disciplinary literacy, and writing—topics scarcely covered in the 2008 U.S. practice guide but which have been extensively researched since then. Finally, I call for revision of the U.S. practice guide and the establishment of standing committees on adolescent literacy to help educators translate the latest research findings into updated practices

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy

COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

Vaccine-associated enhanced respiratory disease (VAERD) was previously observed in some preclinical models of SARS and MERS coronavirus vaccines. We used the SARS-CoV-2 MA10 mouse model of acute lung injury to evaluate the immune response and potential for immunopathology in animals vaccinated with research-grade mRNA-1273. Whole-inactivated virus or heat-denatured spike protein subunit vaccines with alum designed to elicit low-potency antibodies and Th2-skewed CD4+ T cells resulted in reduced viral titers and weight loss postchallenge, but more severe pathological changes in the lung compared to saline-immunized animals. In contrast, a protective dose of mRNA-1273 induced favorable humoral and cellular immune responses that protected from viral replication in the upper and lower respiratory tract upon challenge. A subprotective dose of mRNA-1273 reduced viral replication and limited histopathological manifestations compared to animals given saline. Overall, our findings demonstrate an immunological signature associated with antiviral protection without disease enhancement following vaccination with mRNA-1273

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences