Dextran sulfate sodium colitis facilitates murine colonization by Shiga toxin-producing E. coli: a novel model for the study of Shiga toxicosis

Shiga toxin-producing E. coli (STEC) are globally relevant bacterial pathogens responsible for epidemic outbreaks of hemorrhagic diarrhea with variable progression to potentially fatal systemic Shiga toxicosis. Predictive clinical biomarkers and targeted therapeutic interventions for systemic Shiga toxicosis in diagnosed STEC patients are not available, and the impact of Shiga toxin production on STEC colonization and survival remain unclear. Improved murine models of STEC infection are needed to address knowledge gaps surrounding the gastrointestinal effects of Shiga toxins, as previously published models utilize ablation of host defense responses or microbiota depletion to facilitate colonization and are poorly suited for study of the effects of Shiga toxins on host responses. Dextran sulfate sodium (DSS) colitis in rodents has been associated with outgrowths of commensal E. coli in the literature, suggesting that DSS colitis could open a gastrointestinal niche usable by pathogenic STEC. This DSS colitis-based approach successfully induced susceptibility to robust colonization by two clinical isolate STEC strains in standard C57BL/6 mice. Studies using a Shiga-like toxin 2 (STX2)-producing clinical isolate STEC strain and its paired isogenic STX2 deletion strain (STEC(ΔSTX2)) revealed that STX2 was associated with delayed gastrointestinal clearance of STEC and concurrent reduction in colonic interleukin 23 (IL-23) axis transcripts known to be critical for pathogen clearance in other gastrointestinal pathogen models. In vivo reductions in IL-23 axis transcripts in the DSS+STEC model were supported by decreased IL-23 protein secretion by human macrophage-like cells during Shiga intoxication in vitro. Increased morbidity during STX2-producing STEC infection was associated with renal injury consistent with murine systemic Shiga toxicosis characterized by elevations in renal transcripts of molecular injury markers and histologically apparent renal tubular injury in a subset of mice. The dissertation research establishes a novel model of DSS colitis-facilitated murine STEC infection that recapitulates progression to systemic Shiga toxicosis in a subset of infected mice and demonstrates a clear STEC survival benefit associated with STX2 production. Shiga toxin-induced suppression of IL-23 axis signaling is a novel finding facilitated by the DSS+STEC model, demonstrating its utility for future delineation of the impacts of Shiga toxins on gastrointestinal host responses to STEC

Rights-Based Theories of Accident Law

This article shows that extant rights-based theories of accident law contain a gaping hole. They inadequately address the following question: What justifies using community standards to assign accident costs in tort law? In the United States, the jury determines negligence for accidental harm by asking whether the defendant met the objective reasonable person standard. However, what determines the content of the reasonable person standard is enigmatic. Some tort theorists say that the content is filled out by juries using cost benefit analysis while others say that juries apply community norms and conventions. I demonstrate that what is missing from this exchange is a theory that adequately justifies using a particular way of filling out the content of the objective reasonable person standard. Rights-based theories are particularly guilty of ignoring what I call the central normative concern. That concern is what criterion should determine the amount of precaution an individual must use to avoid being justifiably assigned others’ accident costs. To identify this problem I focus on rights-based theories of accident law. After showing how several rights-based theories of accident law inadequately address the central normative concern, I briefly outline a theory of assigning accident costs that has the potential for offering the best answer to the central normative concern. The most important aspect of this theory, called democratic community standard theory, is that it provides a justification for using community standards to adjudicate tort claims. This justification employs Kantian political theory based on how free and equal individuals would choose to assign accident costs

Managing an Instrumented Protective Systems Program for a Petrochemical Facility

Presentatio

The Democratic Standard Of Care In Tort Law

Social life is inherently risky. Who should bear the costs of accidental harm? That issue has been traditionally addressed in tort legal doctrine under the concept of breach of the negligence standard of care. Trial courts provide juries with instructions that, put roughly, direct the jury to decide whether the defendant’s conduct fell below what a reasonably prudent person would have done if in the defendant’s circumstances. Without further judicial direction on that issue, the jury effectively has excessive discretion in rendering a verdict. Such discretion, opens the door for at least two kinds of potential injustice. Juries could treat like cases differently, and juries can easily ignore or fail to give due consideration to a society’s diverse, irreconcilable, and competing conceptions of the good as to what constitutes reasonable prudence. To mitigate such, I have created “democratic standard theory.” I claim that a theory based on the overarching moral and political commitments of the Kantian tradition can only specify what constitutes negligent breach if it incorporates, as facts, the actual values of the individuals subject to the risk at issue. Since individuals’ comprehensive conceptions of the good conflict, majority rule, constrained by constitutional essentials, should determine what constitutes breach of the negligence standard of care. Thus, in each dispute over negligence in tort, democratic standard theory sets the stakes of negligent risk, especially the costs of accidental harm, in accordance with the values of as many as possible of the individuals locally affected by the particular kind of act at issue

Strategic planning : a case study of behavioral influences in the administrative decisions of middle managers in small independent colleges.

The purpose of this research has been to study the influences of strategic planning on the administrative decisions of middle managers at small independent colleges. The problem was examined and analyzed using a conceptual model which considers institutional history, culture, and leadership. A descriptive research technique, the case study, was used. The design of this study included the relationships between effective strategic planning and the role of middle managers in this institutional planning process. Bentley College was selected as the case study site because it recently introduced an institutional strategic planning process and because it is regarded as a well managed institution. Data sources included institutional archival records, contemporary institutional correspondence and documents, and key-informant interviews. The influence of strategic planning on the managerial behavior of middle managers at this particular institution affected their roles, decision making, and unit planning. Patterns did emerge and the findings are summarized below. 1. Middle managers were involved in all aspects of strategic planning, except the determination of future direction. 2. Strategic planning facilitated increased involvement of middle managers in the institutional decision making process. 3. The strategic planning process facilitated an increased understanding among middle managers of each others unit priorities and goals. 4. Strategic planning facilitated increased unit planning. The findings of this study pertain to one particular independent small college. Although the results of this study do not have significant predictive value, they do provide a better understanding of the middle managers role in strategic planning