Development and Evaluation of Therapeutics in the Setting of Radiation Injury

The possibility of an incident involving radiation exposure is at the forefront of public attention in the current global environment. With a greater number of entities possessing nuclear weapons and increased demand for nuclear power, the concern for uncontained exposure to radiation is increasing. In light of these developments, the need for treatments that may be easily stored and administered to large numbers of people who have been exposed to high doses of total body irradiation (TBI) is more urgent than ever before. Our goal was to identify and develop novel, drug-like small molecules that would exhibit radiomitigating activity for use in Acute Radiation Syndrome (ARS). Hot water extracts of Cat’s Claw containing quinic acid have been shown to possess activity in increasing circulating white blood cells as well as promoting DNA repair. Our group previously synthesized and evaluated a series of quinic acid derivatives. Quinic acid derivative KZ-41 was identified and described as highly water soluble and orally available. We have, therefore, identified a novel quinic acid derivative, KZ-41, as our initial lead molecule for evaluation, characterization, and development in the setting of ARS. Initial efficacy was tested in vivo by evaluating the impact KZ-41 had on the primary endpoint of mortality in lethally irradiated C57BL/6 mice 30 days after exposure. To investigate the potential mechanisms related to the enhanced survival following TBI, we investigated the effect of KZ-41 on parameters important to initial wound healing. We developed an imaging model to specifically investigate the effect of KZ-41 on clotting following TBI and vascular injury. This model also allowed us to gain insight into “combined injury” which is also of critical importance when discussing the “real-life” implications of ARS. . To further evaluate mechanisms of effect, we developed an in vitro model using human monocytes (U937) cells. Using the in vitro model developed, we characterized the effect KZ-41 had on intrinsic and extrinsic apoptotic cell death, focusing on the impact in the “bystander effect” model. We also utilized the in vitro model to identify potential more potent analogues and next-generation compounds. Initial pre-clinical pharmacokinetic characterization of a next-generation compound was also conducted. We have shown KZ-41 to be effective in improving survival of lethally irradiated mice, enhancing the critical wound healing events of initial thrombus formation and in restoring vascular flow in combined injury. In an in vitro bystander effect model, KZ-41 can mitigate apoptosis when administered after the radiation event. Initial, identification, and pharmacokinetic characterization of a potent next-generation compound for use in ARS is also described herein

Teaching Music Theory and History with Collaborative Awareness

The disciplines of music history and music theory are integrally linked: One cannot be studied without the other. Courses in these disciplines are at the core of many undergraduate music degree programs, and upon completing a graduate degree in music at Andrews University, students are expected to demonstrate the ability to synthesize their knowledge in both disciplines. The path towards successfully teaching these skills of synthesis involves awareness and collaboration between teachers in both disciplines, and it involves active inclusion of students’ own choices and goals in the music they study

Merger negotiations with stock market feedback

Merger negotiations routinely occur amidst economically significant a target stock price runups. Since the source of the runup is unobservable (is it a target stand-alone value change and/or deal anticipation?), feeding the runup back into the offer price risks "paying twice" for the target shares. We present a novel structural empirical analysis of this runup feedback hypothesis. We show that rational deal anticipation implies a nonlinear relationship between the runup and the offer price markup (offer price minus runup). Our large-sample tests confirm the existence of this nonlinearity and reject the feedback hypothesis for the portion of the runup not driven by the market return over the runup period. Also, rational bidding implies that bidder takeover gains are increasing in target runups, which our evidence supports. Bidder toehold acquisitions in the runup period are shown to fuel target runups, but lower rather than raise offer premiums. We conclude that the parties to merger negotiations interpret market-adjusted target runups as reflecting deal anticipation.Merger negotiations; stock market feedback

Problems without Ceilings: How Mentors and Novices Frame and Work on Problems-of-Practice

Support for new forms of teaching expertise with rigorous and equitable outcomes for student learning is a particular challenge when communities of actors working together do not share a similar language or vision of teaching practice. For this project we coordinated activities in and outside of secondary science classrooms for Cooperating Teachers (CTs) and their Pre-Service Teachers (PSTs) to inquire into a set of research-based teaching practices and tools. Using frame analysis we contrast three problems of practice addressed by 23 dyads: problems of developing novice teachers, problems of improving teaching, and problems of improving student learning. The last frame, improving student learning, required actors to share and cocreate knowledge with members outside of their dyads. To do this, groups of dyads formed new or repurposed existing social networks to share tools and work on problems “without ceilings,” meaning those that fueled on-going lines of inquiry. We describe ways in which knowledge became shared, actors assumed new roles, and new types of tools, activities, and forms of discourse emerged for contextualizing collective work. This study suggests a need for a systems-level approach to teacher education that focuses on institutional networks of shared tools, practices, and deliberate socio-professional routines for improving practice

The impact of food and nutrition on health and chronic disease: from birth to death

This panel will discuss the importance of nutrition during each life stage, beginning with birth and moving up through aging

Merger Negotiations with Stock Market Feedback

Do preoffer target stock price runups increase bidder takeover costs? We present model-based tests of this issue assuming runups are caused by signals that inform investors about potential takeover synergies. Rational deal anticipation implies a relation between target runups and markups (offer value minus runup) that is greater than minus one-for-one and inherently nonlinear. If merger negotiations force bidders to raise the offer with the runup—a costly feedback loop where bidders pay twice for anticipated target synergies—markups become strictly increasing in runups. Large-sample tests support rational deal anticipation in runups while rejecting the costly feedback loop

The responsiveness of the uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL)

Abstract Background A number of noninvasive alternatives to hysterectomy have become available as treatments for uterine fibroids. These alternative therapies, however, may not relieve all symptoms. Consequently, the need for patient-reported outcomes to assess symptom reduction of uterine fibroids has become increasingly important to evaluate the clinical success of patients who choose these alternative therapies. The purpose of the study was to examine the responsiveness of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) with treatment of uterine fibroids. Methods The responsiveness of the UFS-QOL was assessed as a post-hoc analysis of patients treated with MRI-guided focused ultrasound thermal ablation (MRgFUS) for uterine fibroids. The UFS-QOL and SF-36 were completed at baseline and months 1, 3, and 6. Patient perceived overall treatment effect (OTE) was assessed at month 3, while satisfaction with treatment was collected at month 6. The responsiveness of the UFS-QOL was examined using effect sizes and change scores by patient-reported overall treatment effect and satisfaction. Results A total of 102 women with complete UFS-QOL data were included in the analysis; the mean age was 45 years and 79% were Caucasian. From baseline to 6 months, significant improvements were observed in UFS-QOL Symptom Severity and all Health-Related Quality of Life (HRQL) subscale scores (p Conclusion The UFS-QOL is responsive to treatment for uterine fibroids and is a useful outcome measure for uterine-sparing uterine fibroid treatments.</p

Drawings as Imaginative Expressions of Philosophical Ideas in a Grade 2 South African literacy classroom

This article reports on a philosophy for children (P4C) literacy project in a South African foundation phase classroom that introduces an important new focus in the P4C classroom: the visualisation of philosophical ideas provoked by the picture book The Big Ugly Monster and the Little Stone Rabbit (2004) by Chris Wormell, giving voice to young children’s own imaginative ideas and beliefs (in this case about death). This research shows how a particular use of the community of philosophical enquiry pedagogy combined with the making of drawings necessitates a rethinking of what ‘voice’ means. We conclude that the children’s drawings bring something new into existence, thereby offering unique material and discursive opportunities for all children, including those who otherwise might not have expressed their ideas