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The legacy of budgetary reform has been dismal Promising options, rooted in economic values, seem to fall short when confronted with political realities. Nevertheless, the search continues. The authors argue [...]

Publishing theoretical and empirical research in refereed journals is critical to the development of public administration. The journals allow for the research of old and new ideas in this diverse [...]

The state of capital budgeting theory is going through its growing pains. While traditional literature on capital budgeting is grounded in rational decision-making, Nunn (1990) has suggested that such an approach is too limited to be of significant value. New theories, he argues, need to reflect differences in capital demand and differences in approaches to local policy, thereby reflecting both the economically-rational and other components of capital budgeting. In this study, we examine the rigor of the traditional rational approach and the typology put forth by Nunn. Based on a broad cross-sectional analysis of municipal finance directors, we find that capital budgeting is more complex than usually presented. Yet contrary to the argument by Nunn, we also find that the process is restricted more to internal participants, with limited and targeted participation by the public and other external actors.

money over here, we'll offset it over here, we'll put this money in withholding, take it over here.' |Departments will~ be doing that all through the year.' Another indicated that [...]

Edited by Frans L. Leeuw, Ray C. Rist and Richard C. Sonnichsen, New Brunswick: Transaction Publishers, 1994. Hardcover, $34.95. Pp. 212. Private organizations rely on program review information to react [...]

Professionalism and Urban Reform: An Organizational Perspective on Municipal Finance Abstract: The uncertainty of intergovernmental grants-in-aid in the 1980s has made municipal professionalism an issue that deserves increasing attention. Defining [...]

Uveitis is a sight threatening intraocular inflammation accounting for approximately 10% of blindness worldwide. On the basis of aetiology, disease can be classified as infectious or non-infectious; and by anatomical localization of inflammation as anterior, posterior and panuveitis. Non-infectious uveitis is believed to be autoimmune in nature with Th1 and Th17 cells being identified as the prominent effector cell types. Numerous animal models of autoimmune uveitis were developed contributing to our understanding of this inflammatory condition. The classical peptide-induced experimental autoimmune uveoretinitis (EAU) model resembles human posterior uveitis due to the recurrent/relapsing nature of the disease; while the intraocular inflammation triggered by administration of bacterial lipopolisaccharide (endotoxin-induced uveitis, EIU) mimics closely anterior uveitis. The clinical need for novel, more targeted forms of anti-inflammatory therapy has emerged as currently available therapeutic strategies are associated with a number of adverse effects and intolerance in patients. This review summarises knowledge about existing mouse models of uveitis, discusses mechanisms driving intraocular inflammation and describes possible customised translational treatment strategies that can be potentially used in the clinic to prevent blindness in patients.

Sterile corneal inflammation induced by TLR7/8 and TLR9 agonists causes macrophage adherence to the corneal endothelium and giant macrophage formation in the connective tissue stroma. Macrophage adherence to the inner corneal surface and formation of MGCs in the stroma are common signs of chronic inflammation following corneal infection. To determine whether macrophage adherence (known clinically as KPs) and giant cell formation were specific to innate immune activation via particular TLR ligands, macrophage activation was examined in a murine model of TLR‐mediated corneal inflammation. The corneal epithelium was debrided and highly purified TLR ligands were topically applied once to the cornea of TLR7−/−, TLR9−/−, Cx3cr1gfp/+, CD11ceYFP, and IL‐4−/−mice. At 1 week post‐treatment macrophage activation and phenotype was evaluated in the cornea. Treatment with TLR2, TLR3, TLR4, and TLR5 ligands caused an increase in the number of activated stromal macrophages in the central cornea at 1 week post‐treatment. However, treatment with TLR9 ligand CpG‐ODN and the TLR7/8 ligand R848/Resiquimod led to an accumulation of macrophages on the corneal endothelium and formation of multinucleated giant macrophages in the corneal stroma. We suggest that giant cell formation, which is a characteristic feature of granuloma formation in many tissues, may be a unique feature of TLR9‐ and TLR7/8‐mediated macrophage activation.

Soluble antigen traffics from the corneal surface to the draining lymph nodes without T cell activation, unless there is co‐delivery of a ‘danger’ signal. The transport of antigen to the secondary lymphoid tissue is a central component in the initiation of the adaptive immune response. The mechanism of antigen delivery to the DLN from the avascular cornea has not been fully explored. Previous studies in the mouse have shown that cell‐associated corneal antigen is delivered within 6 h to the eye draining SM DLN via DCs and macrophages. In this study, we used a system in which antigen and the processed p‐MHCII complexes derived from the antigen could be tracked in vivo. We report that soluble antigen applied to an abraded cornea in the mouse is transported rapidly (within 30 min) to the SM DLN, where a proportion is taken up by resident DCs and presented as p‐MHCII complexes, while the larger part is cleared by 8 h. At a later time, a second wave of antigen transport in migratory DCs enters the DLN and participates in further continued antigen presentation. With the use of an antigen‐specific TCR transgenic mouse system, we demonstrate that T cell activation does not occur during the early stages of soluble antigen delivery to LN, even though p‐MHCII complexes are generated. Antigen‐specific T cell activation occurs in the later, presumed cell‐associated phase but requires codelivery of a “danger” signal, such as the TLR ligand CpG. We suggest that the early delivery of soluble antigen is more likely to induce T cell nonresponsiveness (anergy) unless presented in the context of an innate‐immune cell activation (danger) signal.

Microglial cells are the resident macrophages of the central nervous system and participate in both innate and adaptive immune responses but can also lead to exacerbation of neurodegenerative pathologies after viral infections. Microglia in the outer layers of the retina and the subretinal space are thought to be involved in retinal diseases where low-grade chronic inflammation and oxidative stress play a role. This study investigated the effect of systemic infection with murine cytomegalovirus on the distribution and dynamics of retinal microglia cells. Systemic infection with murine cytomegalovirus elicited a significant increase in the number of microglia in the subretinal space and an accumulation of iris macrophages, along with morphological signs of activation. Interferon γ (IFN-γ)–deficient mice failed to induce changes in microglia distribution. Bone marrow chimera experiments confirmed that microglial cells in the subretinal space were not recruited from the circulating monocyte pool, but rather represented an accumulation of resident microglial cells from within the retina. Our results demonstrate that a systemic viral infection can lead to IFN-γ–mediated accumulation of microglia into the outer retinal layers and offer proof of concept that systemic viral infections alter the ocular microenvironment and therefore, may influence the course of diseases such as macular degeneration, diabetic retinopathy, or autoimmune uveitis, where low-grade inflammation is implicated.

We investigated the phenotype of cells involved in leukostasis in the early stages of streptozotocin-induced diabetes in mice by direct observation and by adoptive transfer of calcein-AM–labeled bone marrow–derived leukocytes from syngeneic mice. Retinal whole mounts, confocal microscopy, and flow cytometry ex vivoand scanning laser ophthalmoscopy in vivowere used. Leukostasis in vivoand ex vivoin retinal capillaries was increased after 2 weeks of diabetes (Hb A1c, 14.2 ± 1.2) when either donor or recipient mice were diabetic. Maximum leukostasis occurred when both donor and recipient were diabetic. CD11b+, but not Gr1+, cells were preferentially entrapped in retinal vessels (fivefold increase compared with nondiabetic mice). In diabetic mice, circulating CD11b+cells expressed high levels of CCR5 (P= 0.04), whereas spleen (P= 0.0001) and retinal (P= 0.05) cells expressed increased levels of the fractalkine chemokine receptor. Rosuvastatin treatment prevented leukostasis when both recipient and donor were treated but not when donor mice only were treated. This effect was blocked by treatment with mevalonate. We conclude that leukostasis in early diabetic retinopathy involves activated CCR5+CD11b+myeloid cells (presumed monocytes). However, leukostasis also requires diabetes-induced changes in the endothelium, because statin therapy prevented leukostasis only when recipient mice were treated. The up-regulation of the HMG-CoA reductase pathway in the endothelium is the major metabolic dysregulation promoting leukostasis.

A range of alternatives to human donor tissue for corneal transplantation are being developed to address the shortfall of good quality tissues as well as the clinical conditions for which allografting is contraindicated. Classical keratoprostheses, commonly referred to as artificial corneas, are being used clinically to replace minimal corneal function. However, they are used only as last resorts, as they are associated with significant complications, such as extrusion/rejection, glaucoma, and retinal detachment. The past few years have seen significant developments in technologies designed to replace part or the full thickness of damaged or diseased corneas with materials that encourage regeneration to different extents. This review describes selected examples of these corneal substitutes, which range from cell-based regenerative strategies to keratoprostheses with regenerative capabilities via tissue-engineered scaffolds pre-seeded with stem cells. It is unlikely that one corneal substitute will be best for all indications, but taken together, the various approaches may soon be able to supplement the supply of human donor corneas for transplantation or allow restoration of diseased or damaged corneas that cannot be treated by currently available techniques.