Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus

<p>Abstract</p> <p>Background</p> <p>Sublethal doses of whole brain irradiation (WBI) are commonly administered therapeutically and frequently result in late delayed radiation injuries, manifesting as severe and irreversible cognitive impairment. Neural progenitors within the subgranular zone (SGZ) of the dentate gyrus are among the most radiosensitive cell types in the adult brain and are known to participate in hippocampal plasticity and normal cognitive function. These progenitors and the specialized SZG microenvironment required for neuronal differentiation are the source of neurogenic potential in the adult dentate gyrus, and provide a continuous supply of immature neurons which may then migrate into the adjacent granule cell layer to become mature granule cell neurons. The extreme radiosensitivity of these progenitors and the SGZ microenvironment suggests the hippocampus as a prime target for radiation-induced cognitive impairment. The brain renin-angiotensin system (RAS) has previously been implicated as a potent modulator of neurogenesis within the SGZ and selective RAS inhibitors have been implicated as mitigators of radiation brain injury. Here we investigate the angiotensin converting enzyme (ACE) inhibitor, ramipril, as a mitigator of radiation injury in this context.</p> <p>Methods</p> <p>Adult male Fisher 344 rats received WBI at doses of 10 Gy and 15 Gy. Ramipril was administered beginning 24 hours post-WBI and maintained continuously for 12 weeks.</p> <p>Results</p> <p>Ramipril produced small but significant reductions in the deleterious effects of radiation on progenitor proliferation and neuronal differentiation in the rat dentate gyrus following 10 Gy-WBI, but was not effective following 15 Gy-WBI. Ramipril also reduced the basal rate of neurogenesis within the SGZ in unirradiated control rats.</p> <p>Conclusions</p> <p>Our results indicate that chronic ACE inhibition with ramipril, initiated 24 hours post-irradiation, may reduce apoptosis among SGZ progenitors and/or inflammatory disruption of neurogenic signaling within SGZ microenvironment, and suggest that angiotensin II may participate in maintaining the basal rate of granule cell neurogenesis.</p

On complex interpolation and spectral continuity

Let $[X_0,X_1]_t$, 0 ≤ t ≤ 1, be Banach spaces obtained via complex interpolation. With suitable hypotheses, linear operators T that act boundedly on both $X_0$ and $X_1$ will act boundedly on each $[X_0,X_1]_t$. Let $T_t$ denote such an operator when considered on $[X_0,X_1]_t$, and $σ(T_t)$ denote its spectrum. We are motivated by the question of whether or not the map $t → σ(T_t)$ is continuous on (0,1); this question remains open. In this paper, we study continuity of two related maps: $t → (σ(T_t))^∧$ (polynomially convex hull) and $t → ∂_e(σ(T_t))$ (boundary of the polynomially convex hull). We show that the first of these maps is always upper semicontinuous, and the second is always lower semicontinuous. Using an example from [5], we now have definitive information: $t → (σ(T_t))^∧$ is upper semicontinuous but not necessarily continuous, and $t → ∂_e(σ(T_t))$ is lower semicontinuous but not necessarily continuous

Health Insurance Exchanges

Examining committee: Colleen ChrisingerThe United States’ health care sector is increasingly overwhelmed by the high number of uninsured Americans combined with the ever-rising cost of service provision. Over the last thirty years both federal and state budgets have felt the strain, forcing policymakers and legislators to develop new methods to address the market failure. The Patient Protection and Affordable Care Act (PPACA) of 2010 is one such method. As a groundbreaking piece of health care reform, PPACA strives to increase health care affordability and accessibility for all Americans in both the short and long-term. PPACA has enabled the federal government to institute regulations for states, insurance carriers, businesses and the uninsured as way to increase coverage and control costs. PPACA includes a program for insurance provision called a health insurance exchange (HIX), which all states are required to implement by 2014. The purpose of an HIX is to create an insurance market for individuals and small businesses by grouping them into combined risk pools, and to increase accessibility and coverage to the uninsured population. Given these reforms, the Congressional Budget Office and the Joint Committee on Taxation predict that nearly 32 million people will gain coverage in the non-group market by 2016. Of those, they expect that 23 million will obtain insurance through an HIX (Congressional Budget Office, 2010). Health care reform is not a new phenomenon; in fact, it gained considerable national attention in the early 1990s. Eight states created and implemented health purchasing cooperatives (HPC), the predecessors to current day HIXs, in an attempt to control for the same problems faced today. While deemed largely unsuccessful when evaluated on factors such as market share, new products, price, competitive effect on the market and reduction in the uninsured, HPCs did increase price competition and coverage options for small businesses. However, little research exists that highlights the necessary components for state success based on historical and current reform programs; even less exists on the strategies states should undertake to ensure long-term sustainability and participation. This report analyzes the structural design and methods of implementing an HIX on Oregon’s small business health insurance market from the perspective of insurance carriers. To do so, this research conducts an in-depth study of five state health insurance pooling programs to identify best practices and better understand important features and characteristics that should be considered in the development of Oregon’s HIX. The historical case studies of HPCs in California, Connecticut and Florida are compared with current examples of health insurance exchanges in Massachusetts and Utah. The successes and challenges of HPCs, and the preliminary outcomes of current HIXs, provide valuable lessons for design and implementation strategies. Six indicators for carrier participation guided the analysis: risk adjustment; affordability; accessibility; implementation and administration; agent and broker participation; and marketing strategies. State-specific findings are filtered through the six indicators and then compared with PPACA regulations that mitigate many of the hurdles they faced. The report concludes with practical recommendations for Oregon as it continues planning the implementation of an HIX. Special consideration is given to demographic and market trends in Oregon such as recent unemployment rates and coverage demographics. Additionally, Oregon’s health care reform history as well as Senate Bill 99, which outlines the state’s first steps in HIX development, help inform the likelihood of implementation and political feasibility. After a careful analysis of existing literature, historic and current case studies, and pertinent legislation the authors recommend that Oregon: 1) Establish standard measures for risk assessment amongst insurance carriers inside and outside the HIX; 2) Limit the authorization of young adult plans to the HIX only; 3) Define the role of agents and brokers; and 4) Establish a marketing plan for HIX implementation. This report contributes to the discussion of HIX development by analyzing case studies using an insurance carrier lens and identifying features of success and failure to support effective implementation. Should policymakers utilize this report in the development of organizational structures and strategies for implementation, the authors expect greater long-run sustainability and carrier participation

Nevada Indians in California

This report details visits by Northern Paiutes to central and western California as early as 1846 and continuing through the beginning of the twentieth century. That these visits were not necessarily economically motivated makes this behavior seem somewhat unique in western native history