bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health Policy and the Politics of Evidence
Authors: Milewa Timothy , Barry Christine 
Published: September 2005

Abstract National decisions on the drugs, treatments and medical devices that should be funded through public expenditure are a fundamental element of health policy. But despite a political emphasis upon evidence‐based policy, the results of rigorous clinical trials and statistical modelling techniques rarely speak for themselves. So, does the pre‐eminence traditionally accorded to quantitative data in the medical field underpin policy decisions on a consistent basis? Or are more subtle, less transparent characteristics of context and interaction evident in the shaping of attendant decisions? This article considers these questions by drawing on a study of decision‐making in the National Institute for Health and Clinical Excellence (NICE)—an organization established by the British government in 1999 to decide whether selected health technologies should be made available throughout the National Health Service in England and Wales. In broad terms, the findings point to the primacy of arguments based on quantitatively oriented, experimentally derived data but also to a discursive hegemony of clinicians and health economists in mediating, including or debarring more qualitative, experientially based evidence. A more complex, dynamic understanding of policy governance in the field of health technology appraisal—founded on a discursive appropriation of the idea of the “common good”—goes some way to explaining the persistence of this hegemony despite an avowedly inclusive, plural approach to decision‐making.
Novel multifunctional neuroprotective iron chelator‐monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition
Authors: Zheng Hailin , Gal Shunit , Weiner Lev M. , Bar‐Am Orit , Warshawsky Abraham , Fridkin Mati , Youdim Moussa B. H. 
Published: September 2005

AbstractIron‐dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)‐B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinson's disease, Alzheimer's disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO‐B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO‐B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO‐B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron‐dependent lipid peroxidation in rat brain homogenates with IC50 values (12–16 µm), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 µm were able to attenuate cell death induced by serum deprivation and by 6‐hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti‐Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non‐selective MAO‐A and MAO‐B inhibitor (IC50 < 0.1 µm). However, HLA20 was more selective for MAO‐B but had poor MAO inhibition, with an IC50 value of 64.2 µm. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.
Purification of neuronal inclusions of patients with Huntington's disease reveals a broad range of N‐terminal fragments of expanded huntingtin and insoluble polymers
Authors: Hoffner Guylaine , Island Marie‐Laure , Djian Philippe 
Published: September 2005

AbstractHuntington's disease resulting from huntingtin containing an expanded polyglutamine is associated with aggregates largely confined to neuronal inclusions, and with neuronal death. Inclusions are thought to originate from discrete N‐terminal fragments of expanded huntingtin produced by specific endopeptidases. We have now purified the neuronal inclusions of Huntington's disease brain. When incubated in concentrated formic acid, purified inclusions release a polymer, an oligomer and a broad range of N‐terminal fragments of expanded huntingtin. The fragments and the polymeric forms are linked to each other by non‐covalent bonds as they are both released by formic acid, whereas the polymeric forms themselves are presumably stabilized by covalent bonds, as they are resistant to formic acid. We also demonstrate the presence in affected areas of the brain but not in unaffected areas of a broad range of soluble N‐terminal fragments of expanded huntingtin not yet associated with the inclusions and which are likely to be the precursors of the inclusions. Fragmentation of expanded huntingtin in Huntington's disease must result from the operation of multiple proteolytic activities with little specificity and not from that of a specific endopeptidase; subsequent aggregation of the fragments by covalent and non‐covalent bonds leads to the formation of the inclusions.
Characterization of the BM88 promoter and identification of an 88 bp fragment sufficient to drive neurone‐specific expression
Authors: Papadodima Olga , Sergaki Maritina , Hurel Catherine , Mamalaki Avgi , Matsas Rebecca 
Published: September 2005

AbstractBM88 is a neurone‐specific protein implicated in cell cycle exit and differentiation of neuronal precursors. It is widely expressed in terminally differentiated neurones but also in neuronal progenitors, albeit in lower levels. Thus BM88 expression shows a tight correlation with the progression of progenitor cells towards neuronal differentiation. Here we report the genomic organization and proximal promoter characterization of the human and mouse BM88 genes. Both promoters lie in a CpG island, are TATA‐less and have multiple transcription start sites. Deletion analysis performed on the human BM88 gene revealed an 88 bp minimal promoter fragment that is preferentially active in neural cells. Importantly, this minimal promoter is sufficient to confer specific transcriptional activity in primary neurones, but not in glial cells. Within the promoter region there are four functional Sp1‐binding sites. Simultaneous mutations to all four Sp1 sites results in complete loss of promoter activity. Transactivation experiments revealed that Sp1 directly activates the BM88 promoter while activation also occurs in the presence of neurogenin‐1. Characterization of the promoter elements that control neurone‐specific and developmental expression of BM88 should contribute to the elucidation of the transcriptional networks that regulate the transition from a proliferative neural progenitor to a post‐mitotic neurone.
Regulation of intracellular cyclic GMP levels in olfactory sensory neurons
Authors: Moon Cheil , Simpson Phyllis J. , Tu Yajun , Cho Helen , Ronnett Gabriele V. 
Published: September 2005

AbstractCyclic AMP is the primary second messenger mediating odorant signal transduction in mammals. A number of studies indicate that cyclic GMP is also involved in a variety of other olfactory signal transduction processes, including adaptation, neuronal development, and long‐term cellular responses in the setting of odorant stimulation. However, the mechanisms that control the production and degradation of cGMP in olfactory sensory neurons (OSNs) remain unclear. Here, we investigate these mechanisms using primary cultures of OSNs. We demonstrate that odorants increase cGMP levels in intact OSNs in vitro. Different from the rapid and transient cAMP responses to odorants, the cGMP elevation is both delayed and sustained. Inhibition of soluble guanylyl cyclase and heme oxygenase blocks these odorant‐induced cGMP increases, whereas inhibition of cGMP PDEs (phosphodiesterases) increases this response. cGMP PDE activity is increased by odorant stimulation, and is sensitive to both ambient calcium and cAMP concentrations. Calcium stimulates cGMP PDE activity, whereas cAMP and protein kinase A appears to inhibit it. These data demonstrate a mechanism by which odorant stimulation may regulate cGMP levels through the modulation of cAMP and calcium level in OSNs. Such interactions between odorants and second messenger systems may be important to the integration of immediate and long‐term responses in the setting odorant stimulation.
Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease
Authors: Van Raamsdonk Jeremy M. , Pearson Jacqueline , Bailey Craig D. C. , Rogers Daniel A. , Johnson Gail V. W. , Hayden Michael R. , Leavitt Blair R. 
Published: September 2005

AbstractHuntington disease (HD) is an adult onset neurodegenerative disorder characterized by selective atrophy and cell loss within the striatum. There is currently no treatment that can prevent the striatal neuropathology. Transglutaminase (TG) activity is increased in HD patients, is associated with cell death, and has been suggested to contribute to striatal neuronal loss in HD. This work assesses the therapeutic potential of cystamine, an inhibitor of TG activity with additional potentially beneficial effects. Specifically, we examine the effect of cystamine on striatal neuronal loss in the YAC128 mouse model of HD. We demonstrate here for the first time that YAC128 mice show a forebrain‐specific increase in TG activity compared with wild‐type (WT) littermates which is decreased by oral delivery of cystamine. Treatment of symptomatic YAC128 mice with cystamine starting at 7 months prevented striatal neuronal loss. Cystamine treatment also ameliorated the striatal volume loss and striatal neuronal atrophy observed in these animals, but was unable to prevent motor dysfunction or the down‐regulation of dopamine and cyclic adenosine monophsophate‐regulated phosphoprotein (DARPP‐32) expression in the striatum. While the exact mechanism responsible for the beneficial effects of cystamine in YAC128 mice is uncertain, our findings suggest that cystamine is neuroprotective and may be beneficial in the treatment of HD.
Aquaporin‐4 gene deletion in mice increases focal edema associated with staphylococcal brain abscess
Authors: Bloch Orin , Papadopoulos Marios C. , Manley Geoffrey T. , Verkman A. S. 
Published: September 2005

AbstractBrain abscess is associated with local vasogenic edema, which leads to increased intracranial pressure and significant morbidity. Aquaporin‐4 (AQP4) is a water channel expressed in astroglia at the blood–brain and brain–CSF barriers. To investigate the role of AQP4 in brain abscess‐associated edema, live Staphylococcus aureus (105 colony‐forming units) was injected into the striatum to create a focal abscess. Wild‐type and AQP4‐deficient mice had comparable immune responses as measured by brain abscess volume (∼ 3.7 mm3 at 3 days), bacterial count and cytokine levels in brain homogenates. Blood–brain barrier permeability was increased comparably in both groups as assessed by extravasation of Evans blue dye. However, at 3 days the AQP4 null mice had significantly higher intracranial pressure (mean ± SEM 27 ± 2 vs. 17 ± 2 mmHg; p < 0.001) and brain water content (81.0 ± 0.3 vs. 79.3 ± 0.5 % water by weight in the abscess‐containing hemisphere; p < 0.01) than wild‐type mice. Reactive astrogliosis was found throughout the abscess‐containing hemisphere; however, only a subset of astrocytes in the peri‐abscess region of wild‐type mice had increased AQP4 immunoreactivity. Our findings demonstrate a protective effect of AQP4 on brain swelling in bacterial abscess, suggesting that AQP4 induction may reduce vasogenic edema associated with cerebral infection.
Rizatriptan 10‐mg Wafer Versus Usual Nontriptan Therapy for Migraine: Analysis of Return to Function and Patient Preference
Authors: Pascual Julio , García‐Moncó Carlos , Roig Carles , Yusta Izquierdo Antonio , López‐Gil Arturo ,   on behalf of the eMAX Study Group
Published: September 2005

Background.—More than half of patients with migraine suffer moderate to severe functional disability during migraine attacks.Objective.—To compare effects on functional disability at 2 hours after treating a migraine with rizatriptan 10‐mg wafer versus usual nontriptan therapy for triptan‐naïve patients with migraine.Design.—Open‐label, prospective, two‐attack study conducted at 111 neurology clinics.Methods.—Adult patients with migraine treated two migraine attacks, the first with their usual nontriptan therapy (nonsteroidal anti‐inflammatory drugs, 57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 10‐mg wafer. Patients recorded pain intensity and functional disability at the start, and functional disability at 2 hours, as well as the time of return to normal function.Results.—A total of 1353 patients, 76% of them female, completed the study and were considered evaluable. During first and second migraine attacks, 55% and 63% of patients, respectively, reported severe disability or requiring bed rest. At 2 hours after treatment, the likelihood of experiencing any disability was more than five times greater after usual nontriptan therapy than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to 6.94; P < .001). Rizatriptan was twice as likely to return patients to normal function than usual nontriptan therapy after adjusting for confounding factors (adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all time points up to 6 hours, the speed of return to normal function was 52% faster after rizatriptan therapy (P < .001). Significantly more patients preferred rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most common reasons cited for preference for rizatriptan were faster relief of headache pain and faster return to normal function.Conclusions.—Patients in this study were more likely to experience a return to normal function at 2 hours after receiving rizatriptan than after their usual nontriptan therapy for migraine. The results of this study, using patient‐oriented, clinically relevant endpoints such as functional disability and preference, will help to guide practitioners in making recommendations for acute migraine treatment.
Lumiracoxib Is Effective in the Treatment of Episodic Tension‐Type Headache
Authors: Packman Elias , Packman Barry , Thurston Helen , Tseng Lillian 
Published: September 2005

Objective.—To evaluate the efficacy of single doses of lumiracoxib, the most selective cyclo‐oxygenase (COX)‐2 inhibitor, in the treatment of episodic tension‐type headache (ETTH), with particular emphasis on time to onset of analgesia.Background.—ETTH is the most frequently occurring type of headache with an annual prevalence rate of up to 40%. Some patients with ETTH do not respond to currently available therapies, thus an effective analgesic is needed that provides a rapid onset of analgesia alongside significant pain relief. Lumiracoxib is the most selective COX‐2 inhibitor developed for the treatment of acute and chronic pain.Methods.—In this single‐center, randomized, double‐blind, double‐dummy, placebo‐controlled, parallel‐group study, patients with ETTH were randomly assigned to receive single‐dose lumiracoxib (200 or 400 mg, n = 60 in each group) or placebo (n = 30) within 1 hour of an ETTH. Efficacy was assessed over a 3‐hour period, the primary efficacy variable being the time to onset of analgesia. Other efficacy variables included summed pain intensity difference from 0 to 3 hours after dosing, time‐specific pain intensity difference, time‐specific pain relief, time‐specific pain relief intensity difference, total pain relief over 0 to 3 hours, patient's global evaluation of treatment effect, the proportion of patients who achieved onset of analgesia by 1 hour and time to rescue medication intake. Safety was assessed by monitoring and recording of all adverse events (AEs).Results.—The median time to onset of analgesia was significantly faster for lumiracoxib 200 mg (47 minutes; 95% confidence interval [CI]: 41, 52) and lumiracoxib 400 mg (41 minutes; 95% CI: 36, 48) than for placebo (>3 hours; both P < .001). Both doses of lumiracoxib were significantly superior to placebo for all secondary efficacy variables. There were no AEs recorded in any treatment group.Conclusions.—Single 200 or 400 mg doses of lumiracoxib provided rapid and effective relief from the acute pain associated with ETTH.
LITERATURE REVIEW
Authors: James Judson L. 
Published: September 2005

SETTIING HATIOMALJPRJORITIES: A REVIEW ESSAY Charles L. Schultze, Setting National Priorities: The 1971 BudgetCharles L. Schultze, Edward R. Fried, Alice M. Rivlin, and Nancy H. Teeters, Setting National Priorities: The 1972 BudgetCharles L. Schultze, Edward R. Fried, Alice H. Rivlin, and Nancy H. Teeters, Setting Rational Priorities: The 1973 BudgetEdward R. Fried, Alice M. Rivlin, Charles L. Schultze, and Nancy H. Teeters, Setting National Priorities: The 1974 BudgetBarry M. Blechman, Edward M. Gramlich, and Robert W. Hartman, Setting National Priorities: The 1975 BudgetBarry M. Blechman, Edward M. Gramlich, and Robert W. Hartman, Setting Rational Priorities: The 1976 Budget RECENT RELEVANT LITERATURE Thomas H. Tietenberg and Pierre Toureille, Energy Planning and Policy: The Political Economy of Project IndependenceStanley D. Bachrack, The Committee of one Million: “China Lobby” Politics 1953–1971Otis L. Graham, Toward a Planned Society: From Roosevelt to NixonJudith Innes DeNuefville, Social Indicators and Public Policy: Interactive Processes of Design and ApplicationCole Blasier, The Hovering Giant: U.S. Response to Revolutionary Change in Latin AmericaRichard L. Siegel and Leonard B. Weinberg, Comparing Public Policies; United States, Soviet Union, and EuropeRichard D. Bingham, The Adoption of Innovation by Local GovernmentHenry J, Pratt, The Gray Lobby BOOK NOTES Marc Karnis Landy, The Politics of Environmental Reform: Controlling Kentucky Strip MiningAllen C. Ornstein and Steven I. Miller, eds., Policy Issues in EducationColm A. O'Muircheartaigh and Clive Payne, eds., Exploring Data StructuresColm A. O'Muircheartaigh and clive Payne, eds., Model FittingRechard A. Posner, Antitrust Law: An Economic PerspectiveLawrence L. Whetten, ed., The Future of Soviet Military Power THE PROS AND CONS OF SYSTEMS ANALYSIS IN POLICY STUDIES A BIBLIOGRAPHY OF SPECIFIC PROBLEM AREAS WITHIN POLICY STUDIES
A Review, Comparison, and Evaluation of Some State & Local Data Handbooks
Authors: James Judson L. 
Published: September 2005

Bureau of the Census, 1972 Census of GovernmentsBureau of the Census, Local Government Finances in Selected Metropolitan Areas and Large Counties: 1974–75Bureau of the Census, City Government Finances in 1974–75International City Management Association, The Municipal Year‐book, 1977Paul Albright, ed., The Book of the States, 1976–77
Historical Experience
Authors: Medelski George 
Published: September 2005

ABSTRACTThe theory of long cycles is a set of propositions about the behavior of the global political system. It has its roots in a tradition of “oceanic” thought and it may be contrasted with two more conventional models of world politics, the states‐system model and the imperial model. The theory offers a basis for strategic analysis and for the derivation of policy implications: The United States is seen as successor to a line of world powers; this world role calls for a defensive strategy that would avoid the “imperial presumption”; on past experience another global war is not imminent in the present phase of the long cycle; the major immediate problem is the nationalist phase of the cycle; but the long‐term problem confronting the global system is the decay of its political structure.
STATE COMPLIANCE WITH WORKMEN'S COMPENSATION RECOMMENDATIONS
Authors: Thompson Joel A. 
Published: September 2005

ABSTRACTThe Occupational Safety and Health Act of 1970 established the National Commission on State Workmen's Compensation Laws. The National Commission was directed to “undertake a comprehensive study and evaluation of State workmen's compensation laws in order to determine if such laws provide an adequate, prompt, and equitable system of compensation”. In 1972 the Commission issued its report, and “criticized many aspects of state workmen's compensation programs”. In its report the Commission made eighty–four recommendations for a “moder” workmen's compensation program and designated nineteen of these as “essential”. This research traces state progress in complying with each of these nineteen essential recommendations. Between 1972 and 1977 many states made significant improvements in their workmen's compensation programs and overall there was a 34 percent increase in compliance during this period. Higher levels of compliance were found to be related to two factors: changes in industrial diversification and the involvement and activity of vitally concerned interest groups.
The Odd Compartmentalization: Public Opinion, Aggregate Data, and Policy Analysis*
Authors: Obler Jeffrey 
Published: September 2005

ABSTRACTThis article examines some of the assumptions that underlie the use of aggregate data for policy analysis, In particular, it explores the consequences of the assumption of antagonistic attitudes between “haves” and “have nots” on social welfare policies. Use of public opinion data demonstrates the low salience of regressiveness of taxation and thereby calls into question the validity of a common indice in aggregate analysis. The use of this and related examples is intended to demonstrate the value of supplementing aggregate data analysis of public policy with direct evidence about public attitudes toward those policies.
The Politics of Termination: Concepts and Process
Authors: Bothun Douglas , Comer John C. 
Published: September 2005

ABSTRACTThis article clarifies some of the theoretical issues relevant to the concept of termination of public policies. It distinguishes between functional and structural termination, considering the first to reflect an end to policy or program activities, the second to reflect an end to institutional arrangements that have responsibility for policies or programs. Their Interrelationship is analyzed. The authors find that few programs or policies are terminated; fewer bureaus, agencies, or departments are eliminated. In fact, efforts at termination occasionally lead to an expansion of resources. An application of these concepts and this framework in the case of community health care in Nebraska demonstrates their potential utility for understanding termination.
Executive Policy‐Making Authority and Using Zero‐Base Budgeting for Allocating Resources
Authors: Gordon Lawrence A. , Schick Allen 
Published: September 2005

ABSTRACTThe objective of this article is to examine how executive policy‐making authority is affected by allocating public resources via zero‐base budgeting (ZBB). After reviewing the concept and rationale of ZBB, the article compares incremental policy‐making with scientific policy‐making. This review and comparison are then used to draw implications of using ZBB. Ultimately the article argues that ZBB will result in greater policy‐making authority in the hands of senior management of the executive branch at the expense of the legislative agencies and bureaus. Thus, government's responsiveness toward the particularistic interests of individuals and groups will be reduced as a result of using ZBB.
HOUSING ALLOWANCES AND DEMAND ORIENTED HOUSING SUBSIDIES
Authors: Quigley John M. 
Published: September 2005

ABSTRACTIt is estimated that the Federal government will spend more than $170 million on the Experimental Housing Allowance Program (EHAP). So far more then $50 million has been spent on EHAP research alone. This paper indicates some of the analytical issues in evaluation and suggests that housing allowance policies have ample historical precedent.