We prove a number of general theorems about CZK, the class of problems possessing computational zero knowledge proofs. Our results are unconditional, in contrast to most previous works on CZK which rely on the assumption that one-way functions exist. We establish several new characterizations of CZK, and use these characterizations to prove results such as: 1) Honest-verifier CZK equals general CZK. 2) Public-coin CZK equals private-coin CZK. 3) CZK is closed under union (and more generally, "monotone formula closure"). 4) CZK with imperfect completeness equals CZK with perfect completeness. 5) Any problem in CZK /spl cap/ NP can be proven in computational zero knowledge by a BPP/sup NP/ prover. 6) CZK with black-box simulators equals CZK with general, non-black-box simulators. The above equalities refer to the resulting class of problems (and do not necessarily preserve other efficiency measures such as round complexity). Our approach is to combine the conditional techniques previously used in the study of CZK with the unconditional techniques developed in the study of SZK, the class of problems possessing statistical zero knowledge proofs. To enable this combination, we prove that every problem in CZK can be decomposed into a problem in SZK together with a set of instances from which a one-way function can be constructed.
The French health-care system is almost totally under the supervision of the government, which defines the general orientation of health policy. For example, a health-care policy for cancer treatment will be developed in France within the next 5 years. The government organizes the initial formation of all categories of health professionals and so controls the number of professionals in each category. In France, 4500 medical students graduate each year. Demographic problems at the present time are caused by the quota for all medical professions. The government also ensures that the number and location of hospitals are adequate for the needs of the French population. It supervises public hospitals and the management of private clinics, with the objective of providing a consistent standard of care in all health-care structures. The government also proposes the health budget for parliament's approval. In 1996, in line with the concept of decentralization, which means ‘to think globally but act locally’, regional agencies for hospital care were created in each administrative region. They are responsible for the strategic and economic supervision of hospitals, and for the organization of regional health care. However, they have no authority with regard to ambulatory care, thus creating a gap between hospital and ambulatory care in France, which represents a great obstacle to the coordination of care for disabled and elderly people. The French health-care system is a mixed system, being both etatic and liberal. There is a collective health insurance program in place based on incomes; the premium payments are automatically deducted from salaries. The rate is determined each year by the government for an equilibrated budget. Patients have completely free access to all medical care, including hospitals and choice of practitioners. They can have as many consultations and hospitalizations as they want. Furthermore, public and private health structures coexist. Sixty-five percent of hospitals are public and 35% are private. Ambulatory care structures are mainly private (95%). Therefore, although the French system is complex, comprising etatic and private organizations, it functions well. Furthermore, freedom and heterogeneity are probably the main guarantees of quality of health care in France, even if the cost is high and constantly increasing. In France, the number of available hospital beds for acute care (short-stay units), rehabilitation, long-term care and psychiatry is high (Table 1). The rates per 1000 people are the highest in Europe. However, the number of beds for disabled geriatric patients is low: 400 000 beds in retirement homes and 68 000 beds in long-term care units. There is a very long queue to get into such establishments. For psychiatric institutions, there are a total of 6430 beds. The number of health professionals is quite high (Table 2), but they are growing older and demographic problems will arise in the next 10 years. To finance the health-care system, including ambulatory and hospital care, a budget is approved by parliament annually. Ten percent of the gross domestic product (GDP) is devoted to the health-care system (130bn euros), including public hospitals, private hospitals, ambulatory care organizations and pharmacies (Table 3). The budget is being constantly increased. Patients can get a refund of the total cost of health care. For example, refunds for hospitalization costs are between 80% and 100%. For ambulatory care, refunds are between 70% and 100% and for drugs, between 35% and 100%. Health care is free for the homeless and poor people (100% refund). There is a list of 30 severe diseases, including Alzheimer's disease (AD), for which patients are entitled to a 100% refund. Last year, the treatment of AD was listed as a national priority and the government established a care program for the disease. Two main initiatives were proposed. The first one is diagnosis, particularly early diagnosis, as only half of the patients are diagnosed in France. In regard to this, the program proposed the development of memory clinics and regional expert centers. The second initiative is to provide better care for people with AD. This covers ethical issues, the possibility of family caregivers benefiting from some help, financial aid, and the creation of social day-care centers. Hospital care for people with AD is totally paid for by the social security system. Various options are available: short-stay units, rehabilitation units, and day hospitals (of which there are too few) for diagnosis and rehabilitation. Furthermore, people with AD are generally not very welcome in traditional short-stay and rehabilitation units, and it is very difficult to get them a place in such units. Memory clinics are being developed and regional expert centers will be created next year to assist in the early diagnosis of the disease. An expert center must meet specific defined criteria. It must have a multidisciplinary team (neurologists, geriatricians, psychiatrists, and neuropsychologists) and a day hospital for disease diagnosis (capable of handling at least 100 new patients a year). It must also be a source of expertise in research, possess postgraduate knowledge about dementia, and be the centre of a network including general practitioners, ambulatory neurologists and memory clinics of the first degree. Ambulatory care for people with AD is provided by neurologists and psychiatrists (both in insufficient numbers), and by general practitioners, who are not accurately trained for dementia care. Very few geriatricians are included in ambulatory care. Nurses, orthophonists, and physiotherapists are also involved, but again, they are insufficient in number. In other words, social day-care centers should be developed. Social support for patients is financed by a new prestation, the ‘APA’ (personalized prestation for the promotion of autonomy). This prestation was defined in 2002. The amount of the prestation is calculated according to the loss of autonomy. Patients are classified into six groups upon evaluation of their autonomy. It is possible for patients to buy the time of professional social workers and caregivers. The highest level of financial aid they can obtain is 1200 euros per month. Today, 50% of patients are being looked after only by family caregivers. Nursing homes are currently evolving in France. Retirement homes and long-term care units now belong to a single category. The total living expenses comprise three parts: food and housing costs are borne by the patients (through family or social aid); nursing costs are covered by the APA prestation and patients (or their families); and the total cost of medical care is covered by social security (100%). In conclusion, the French health-care system is quite unique since it involves both etatic and liberal organizations. It is an excellent system for patients because of low medical costs, but it requires a high cost of maintenance.
In America free public education is a constitutional value. Yet, although free public education
for all is a constitutional value, America's public schools remain ravaged by savage
inequalities, many of which are the direct result of significant financial disparities. Given
the obvious conflict between the constitutional value of free public education for all and the
funding parities created by the States' school finance systems, it is not surprising that the
courts have been asked to intervene and vindicate the constitutional value of free public
education for all by declaring that the current system of financing the schools is
unconstitutional. However, a judicial solution to the problem has proved as elusive as a
legislative or executive solution. Paradoxically, a major reason for the States' failure to adequately finance the
achievement - the constitutional value of quality education for all - is the existence of other
constitutional values. In other words, there are values within the American constitutional
system that make it extremely difficult to achieve another constitutional value. This article
explains how two American constitutional values - judicial restraint and decentralization -
work together to prevent adequate funding of another constitutional value - a quality education
for all.
European patents on a number of therapeutic biopharmaceutical agents will expire in 2004 and 2005. These agents and others recently past patent expiry include recombinant human growth hormone, alpha and gamma interferons, streptokinase, interleukin (IL)-2, insulin, glucerase, plasminogen activator, granulocyte colony-stimulating factor, and erythropoietin. Patent expiry for these products opens the door for the development and marketing of generic versions of these drugs, also known as biosimilars or follow-on biologics. The successful introduction of biosimilars into the pharmaceutical market will depend on the establishment of regulatory guidelines that have been adapted for approval of these generic biopharmaceutical agents. Recombinant therapeutic proteins differ significantly from classic small drug molecules, such as diazepam and prednisone, in their size, molecular heterogeneity and complexity, and methods of manufacture. In contrast with classic drugs, it is currently impossible to fully predict the biological characteristics of therapeutic proteins using physicochemical methods. For these reasons, guidelines for demonstrating bioequivalence of biosimilars with approved innovative products must be specially tailored to the characteristics of these molecules. The criteria for regulatory approval of biosimilars differ from those used to evaluate follow-on versions of classic drugs. During the revision of European (EU) legislation concerning medicinal products, the controversial regulatory and patent issues for marketing of biosimilars led to revamping of the regulations by the European Parliament in May of 2004 [1,2]. The revised regulations provide a clearer and more expedient route for developing and testing generic products within the period of protected data exclusivity (8 years for the reference product), and guidance regarding when generics may be sold following expiration of the reference product patent. There is much at stake in establishing regulatory guidelines for approval of biosimilars in terms of the total potential market for these products (approximately US $20 billion, or 24 billion Euros, by 2005) [3]. In addition to the standard demonstration of safety and efficacy, development and marketing approval of biosimilars are complicated by several factors, including: the technically complex methods required to manufacture and characterize biopharmaceutical proteins; susceptibility of these proteins to physical and chemical degradation during and after manufacture; and the observed immunogenicity of several approved biologics such as recombinant streptokinase [4], interferon-beta [5], GM-CSF [6], hirudin, interleukin (IL)-2 [7] and, more recently, epoetin alfa [8], which can lead to neutralization of these biologic agents and lack of efficacy or sometimes severe, adverse reactions. Immunologic safety will be an increasingly important criterion for evaluating the safety of biosimilars, especially in light of the recently observed increase in cases of antibody (Ab)-mediated pure red cell aplasia (PRCA) [9,10]. These cases have been associated primarily with subcutaneous (SC) administration of epoetin alpha (Eprex®, Ortho Biologics LLC, Manati, Puerto Rico), which was reformulated in 1998. Establishing proper and comprehensive guidelines for biosimilars is further complicated by the absence of clear-cut criteria and methods for determining their potential immunogenicity. Preclinical in vitro or in vivo surrogate markers of immunogenicity are not always available or representative of immune responses in patients [11]. Therefore, the definitions for bioequivalence of biosimilars with approved products will likely differ from definitions used for bioequivalence of classic drugs [12,13]. The pharmaceutical and biotechnology industries have different viewpoints from generic drug manufacturers on what is required for evaluating the safety and efficacy of biosimilars for regulatory approval [14,15]. Innovator companies explain that the complexities of manufacture and process validation, the intrinsic heterogeneity of biopharmaceutic products, and the potential immunogenicity of products manufactured by different processes preclude reliance on in vitro surrogates of activity alone for evaluating substitutability of biosimilars [14]. For these reasons, innovator companies maintain that full-fledged clinical trials are required to demonstrate the substitutability and safety/efficacy of biosimilar products. In contrast, manufacturers of biogeneric products argue that surrogate in vitro or in vivo assays that mimic the absorption kinetics and dose–response of reference drugs may be sufficient to demonstrate bioequivalence of biosimilars. These assays can be performed in the absence of large, controlled clinical studies, which are required for approval of pioneer drugs [10,15]. The situation with demonstrating immunologic safety is more problematic, especially with products with a low incidence of immunogenicity. The European Committee for Human Medicinal Products (CHMP) states that the potential immunogenicity of biosimilar products should be evaluated at the preclinical and clinical stages using validated state-of-art techniques, including animal models, physicochemical methods, and computer algorithms [12,16]. However, the lack of standardization of assays for detecting Abs against therapeutic proteins is a major hurdle because of differences in procedure and calibration, assay sensitivity, and other factors [16]. For example, the potential immunogenicity of erythropoiesis-stimulating agents (ESAs), including epoetin, is confounded by the undefined mechanism of the Ab response to these recombinant proteins, with respect to contributing product characteristics or any predisposing patient factors. There is a need for an appropriate in vivo model to fully evaluate the immunogenicity of new ESAs or biosimilars because of the potential development of an immunopathology such as Ab-mediated PRCA [10]. Such a deleterious consequence of treatment underscores the need to unequivocally demonstrate immunologic safety for ESAs and their biosimilars in addition to the classic parameters of safety, efficacy, and bioequivalence [11]. The ultimate proof of immunologic safety of ESAs and other therapeutic proteins will come from results of clinical studies and post marketing analyses [10]. In conclusion, the development of Ab-mediated PRCA in patients receiving reformulated erythropoietin underscores the problems associated with maintaining safety and efficacy of approved products following changes in manufacture. Alterations in protein structure or stability can result in serious reactions in patients or loss of therapeutic efficacy. For these reasons, rigorous criteria must be established by the medical, manufacturing, and regulatory communities to protect patients from adverse immune responses to therapeutic recombinant proteins, in general, and biosimilars in particular. These same criteria will also help to establish standards of manufacture and process validation that can be used by all biopharmaceutical manufacturers. Ultimately, these criteria will ensure the safety and efficacy of biosimilars while reducing the potential for immune neutralization of therapeutic proteins or severe treatment-related complications.
What is best strategy to reach the Millennium Development Goal of basic education for all will depend on the specific country context.This paper introduces an input-output method to estimate the financial inputs required to achieve the MDG for primary education and an additional target of enhancing access to secondary education. 1As such the approach followed here is not new, but the innovative element is combining educational demand and supply variables considering both cost dimensions and quality of services as measured among others through test scores (outcomes), quality of school inputs and the nature of delivery of services (privatepublic, centralized or decentralized).We take the following analytical steps: (i) define a production function for specific education outputs (enrolment), (ii) isolate the main determinants of such output (considering both demand and supply factors); (iii) estimate costs per unit of producing such output, and -based on estimated elasticity's and unit costs ensuing from the education production function -(iv) calculate the financing needs of reaching key education goals.We find that determinants of access to schooling are significantly different for urban and rural and for poor and non-poor children.Furthermore, the determinants also differ when referring to access to primary or secondary education.Quality of school inputs does matter in all cases though to varying degree.Particularly, class size, shares of trained teachers and greater school autonomy (in hiring teachers and managing schools) are relevant.Quality of education outcomes, i.e. test scores, while very poor in Ecuador does not seem to influence school enrolment.The upshot is that with a more cost-effective use of resources for primary education, the MDG target of 100% of net primary school enrolment in urban areas is within reach in a period of 4 to 5 years at virtually no additional budgetary cost.Meeting the target for the rural population seems more complicated.In secondary education, important progress can be made to reach a target of 70% net enrolment (with important expected positive externalities for economic growth) by enhancing the share of trained teachers, expand coverage of school demand subsidies and improve class infrastructure.This target is within reach for the poor and non-poor urban population by 2007 at an estimated additional cost of 1 Vos is with the Institute of Social Studies (ISS), The Hague and the Free University Amsterdam.Ponce is with FLACSO-Ecuador and is also a PhD candidate at ISS.
OBJECTIVE: To assess the equity and fairness of the Mexican health system reform that occurred in the late 1990's. MATERIAL AND METHODS: The Mexican reform process was evaluated using the benchmark-system designed by Daniels et al. This benchmark system was adapted to the Mexican setting by adding specific indicators. A documentary review of the Mexican reform process was conducted to score its performance for each benchmark. RESULTS: Except for housing and nutrition components, the reform included few actions related to health determinants. For health care, the main reform initiatives were those related to extending the coverage of essential health services and decentralizing health care provision to the states. Reform initiatives included few activities related to fair financing, tiering, emphasis on second and third level care, accountability, and transparency. CONCLUSIONS: The late nineties reform of the Mexican health system had some positive effect on access of the poor to health care and administrative efficiency, but little impact on fair financing, quality of care, and democratic governance. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
For a variety of reasons, many developing countries especially since the 1990s have embarked on programmes of democratic decentralization that are aimed at creating local self-governing systems that are democratic, relatively autonomous and effective in delivering services.Finding independent sources of financing for these emerging, locally based organs of governance has been one of the central challenges that confront these efforts in most countries.The literature suggests that sources of independent local government revenue are few in poor countries.As a result, most countries design decentralization programmes that depend heavily on intergovernmental transfers from national to local governments.Given widespread poverty that exists in most developing countries, this is a crucial strategy.However, the problem is that many central governments are engulfed in a systemic financial crisis and are desperately exploring strategies for reducing their expenditure commitments.One outcome is that revenue transfers are often irregular or fall much below the levels of expenditure decentralization, leading to serious fiscal gaps at the local level.Even where transfers are adequate and reliable, a fiscal regime which compels local actors to depend so heavily on central financial arrangements for practically all of their expenditure requirements undermines the development of lateral (local state-citizen) rather than vertical (central-local state) relations within the state, with serious implications for public participation and effective accountability.In the meantime, cities of developing countries continue to grow phenomenally in a way that makes conventional strategies for financing urban infrastructures unsustainable.Many analysts view this rapid urbanization as fatally aggravating the problem of urban/local governance.This paper suggests a different and more positive view.It reviews the literature which concedes that property taxation remains largely untapped and might indeed be progressive in developing countries.This literature highlights mainly the technical constraints to progress-assessment, valuation and collection.In contrast, this paper contends that the tax suffers from a combination of political and technical factors where the latter are dependent not independent variables.The paper undertakes an analysis of the key stakeholders in implementing successful property taxation policies based on research conducted in four countries-India, Nigeria, Republic of South Africa and Zimbabwe in the early 1990s.The paper suggests that willingness, opportunity and capacity remain critical factors and demonstrates how opposition to the tax can be overcome by strategic partnerships between central and local governments, public and private and domestic and external actors.
This paper examines the concept and practice of community participation in World Bank-supported health sector reforms in Asia, and how far such participation has strengthened accountability with regard to provision of sexual and reproductive health (SRH) services. It argues that the envisaged scope of community participation within a majority of reforms in Asia has been limited to programme management and service delivery, and it is occurring within the boundaries of priorities that are defined through non-participatory processes. Setting up of community health structures, decentralization and community financing are three important strategies used for promoting participation and accountability within reforms. The scant evidence on the impact of these strategies suggests that marginalized groups and sexual and reproductive rights based groups are poorly represented in the forums for participation, and that hierarchies of power between and amongst health personnel and the public play out in these forums. Community financing has not lead to enhanced service accountability. As a result of the above limitations, community participation in health sector reforms has rarely strengthened accountability with respect to provision of comprehensive SRH services. In this context, rights (including sexual and reproductive) based groups and researchers need to engage with design, monitoring and evaluation of health sector reforms, both from inside as participants and outside as pressure groups. Participation contracts enhancing powers of civil society representatives, quotas for participation (for women, other marginalized groups and rights-based organizations), and investment in capacity building of these stakeholders on leadership and sexual reproductive rights and health are pre-requisites if participation is to lead to health and SRH service accountability. Community participation and service accountability hence requires more and not less investment of resources by the state.
We study two group theoretic problems, GROUP INTERSECTION and DOUBLE COSET MEMBERSHIP, in the setting of black-box groups, where DOUBLE COSET MEMBERSHIP generalizes a set of problems, including GROUP MEMBERSHIP, GROUP FACTORIZATION, and COSET INTERSECTION. No polynomial-time classical algorithms are known for these problems. We show that for solvable groups, there exist efficient quantum algorithms for GROUP INTERSECTION if one of the underlying solvable groups has a smoothly solvable commutator subgroup, and for DOUBLE COSET MEMBERSHIP if one of the underlying solvable groups is smoothly solvable. We also study the decision versions of STABILIZER and ORBIT COSET, which generalizes GROUP INTERSECTION and DOUBLE COSET MEMBERSHIP, respectively. We show that they reduce to ORBIT COSET under certain conditions. Finally, we show that DOUBLE COSET MEMBERSHIP and DOUBLE COSET NONMEMBERSHIP have zero knowledge proof systems.
Each year, up to three million deaths due to malaria and close to five billion episodes of clinical illness possibly meriting antimalarial therapy occur throughout the world, with Africa having more than 90% of this burden. Almost 3% of disability adjusted life years are due to malaria mortality globally, 10% in Africa. New information is presented in this supplement on malaria-related perinatal mortality, occurrence of human immunodeficiency virus in pregnancy, undernutrition, and neurologic, cognitive, and developmental sequelae. The entomologic determinants of transmission and uses of modeling for program planning and disease prediction and prevention are discussed. New data are presented from the Democratic Republic of the Congo, Tanzania, Ethiopia, and Zimbabwe on the increasing urban malaria problem and on epidemic malaria. Between 6% and 28% of the malaria burden may occur in cities, which comprise less than 2% of the African surface. Macroeconomic projections show that the costs are far greater than the costs of individual cases, with a substantial deleterious impact of malaria on schooling of patients, external investments into endemic countries, and tourism. Poor populations are at greatest risk; 58% of the cases occur in the poorest 20% of the world's population and these patients receive the worst care and have catastrophic economic consequences from their illness. This social vulnerability requires better understanding for improving deployment, access, quality, and use of effective interventions. Studies from Ghana and elsewhere indicate that for every patient with febrile illness assumed to be malaria seen in health facilities, 4-5 episodes occur in the community. Effective actions for malaria control mandate rational public policies; market forces, which often drive sales and use of drugs and other interventions, are unlikely to guarantee their use. Artemisinin-based combination therapy (ACT) for malaria is rapidly gaining acceptance as an effective approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria vaccine becomes deployed, consideration must be given to disease burden, cost-effectiveness, financing, delivery systems, and approval by regulatory agencies. Key to evaluation of vaccine effectiveness will be collection and prompt analysis of epidemiologic information. Training of persons in every aspect of malaria research and control is essential for programs to succeed. The Multilateral Initiative on Malaria (MIM) is actively promoting research capacity strengthening and has established networks of institutions and scientists throughout the African continent, most of whom are now linked by modern information-sharing networks. Evidence over the past century is that successful control malaria programs have been linked to strong research activities. To ensure effective coordination and cooperation between the growing number of research and control coalitions forming in support of malaria activities, an umbrella group is needed. With continued support for scientists and control workers globally, particularly in low-income malarious countries, the long-deferred dream of malaria elimination can become a reality.
For the surveillance of transmissible spongiform encephalopathies (TSEs) in animals and humans, the discrimination of different TSE strains causing scrapie, BSE, or Creutzfeldt-Jakob disease constitutes a substantial challenge. We addressed this problem by Fourier transform-infrared (FT-IR) spectroscopy of pathological prion protein PrP27–30. Different isolates of hamster-adapted scrapie (263K, 22A-H, and ME7-H) and BSE (BSE-H) were passaged in Syrian hamsters. Two of these agents, 22A-H and ME7-H, caused TSEs with indistinguishable clinical symptoms, neuropathological changes, and electrophoretic mobilities and glycosylation patterns of PrP27–30. However, FT-IR spectroscopy revealed that PrP27–30 of all four isolates featured different characteristics in the secondary structure, allowing a clear distinction between the passaged TSE agents. FT-IR analysis showed that phenotypic information is mirrored in β-sheet and other secondary structure elements of PrP27–30, also in cases where immunobiochemical typing failed to detect structural differences. If the findings of this study hold true for nonexperimental TSEs in animals and humans, FT-IR characterization of PrP27–30 may provide a versatile tool for molecular strain typing without antibodies and without restrictions to specific TSEs or mammalian species. For the surveillance of transmissible spongiform encephalopathies (TSEs) in animals and humans, the discrimination of different TSE strains causing scrapie, BSE, or Creutzfeldt-Jakob disease constitutes a substantial challenge. We addressed this problem by Fourier transform-infrared (FT-IR) spectroscopy of pathological prion protein PrP27–30. Different isolates of hamster-adapted scrapie (263K, 22A-H, and ME7-H) and BSE (BSE-H) were passaged in Syrian hamsters. Two of these agents, 22A-H and ME7-H, caused TSEs with indistinguishable clinical symptoms, neuropathological changes, and electrophoretic mobilities and glycosylation patterns of PrP27–30. However, FT-IR spectroscopy revealed that PrP27–30 of all four isolates featured different characteristics in the secondary structure, allowing a clear distinction between the passaged TSE agents. FT-IR analysis showed that phenotypic information is mirrored in β-sheet and other secondary structure elements of PrP27–30, also in cases where immunobiochemical typing failed to detect structural differences. If the findings of this study hold true for nonexperimental TSEs in animals and humans, FT-IR characterization of PrP27–30 may provide a versatile tool for molecular strain typing without antibodies and without restrictions to specific TSEs or mammalian species. Transmissible spongiform encephalopathies (TSEs) 1The abbreviations used are: TSE, transmissible spongiform encephalopathy; BSE, bovine spongiform encephalopathy; FT-IR, Fourier-transform infrared; mAb, monoclonal antibody; TBS, Tris-buffered saline; BE, brain equivalents; TME, transmissible mink encephalopathy; dpi, days postinfection. such as scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans are invariably fatal neurodegenerative disorders of the central nervous system. After the initial reports on the emergence of BSE and variant Creutzfeldt-Jakob disease, in 1986 and 1996, respectively, compelling evidence has gradually accumulated that the latter can most likely be attributed to transmissions, presumably via contaminated food, of BSE agent from cattle to man (1Bruce M.E. Will R.G. Ironside J.W. McConnell I. Drummond D. Suttie A. McCardle L. Chree A. Hope J. Birkett C. Cousens S. Fraser H. Bostock C.J. Nature. 1997; 389: 498-501Crossref PubMed Scopus (1727) Google Scholar, 2Cousens S.N. Linsell L. Smith P.G. Chandrakumar M. Wilesmith J.W. Knight R.S.G. Zeidler M. Stewart G. Will R.G. Lancet. 1999; 353: 18-21Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 3Hill A.F. Desbruslais M. Joiner S. Sidle K.C. Gowland I. Collinge J. Doey L.J. Lantos P. Nature. 1997; 389: 448-526Crossref PubMed Scopus (1208) Google Scholar, 4Scott M.R. Will R. Ironside J. Nguyen H.O.B. Tremblay P. DeARmond S.J. Prusiner S.B. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 15137-15142Crossref PubMed Scopus (462) Google Scholar). Therefore, effective infection control measures for the containment and repression of BSE have become a matter of crucial importance to public health. According to the present state of knowledge, the countermeasures implemented in response to the BSE epidemic are expected to minimize or even eliminate the risk of new primary variant Creutzfeldt-Jakob disease infections of humans directly originating from bovines (5Bradley R. Rabenau H.F. Cinatl J. Doerr H.W. Prions: A Challenge for Science, Medicine, and the Public Health System. S. Karger AG, Basel, Switzerland2004: 146-185Google Scholar). However, further challenges in the area of infection control arise from the hypothetical risk that the BSE agent might have spread via contaminated feed such as meat and bone meal to sheep (5Bradley R. Rabenau H.F. Cinatl J. Doerr H.W. Prions: A Challenge for Science, Medicine, and the Public Health System. S. Karger AG, Basel, Switzerland2004: 146-185Google Scholar) and that BSE, like scrapie, might now be sustained in the ovine population. The clinical symptoms of scrapie, which has been endemic in sheep for centuries without any apparent association with human disease, cannot be reliably distinguished from those exhibited by experimentally challenged BSE-infected ovines. “While it is possible to demonstrate the presence of a TSE by several laboratory techniques using microscopy, electron microscopy, or immunological methods which detect the abnormal form of the prion protein, distinguishing between one strain of scrapie and another, and between BSE and scrapie, is not straightforward” (6, Spongiform Encephalopathy Advisory Committee (1999) http://www.seac.gov.uk/publicats/sub-rep.pdf,Google Scholar). So far, reliable differentiation of BSE and scrapie in sheep has required time-consuming and expensive strain-typing in mice using lesion profiles (7Fraser H. Dickinson A.G. J. Comp. Pathol. 1973; 83: 29-40Crossref PubMed Scopus (279) Google Scholar). Therefore, the development of new methods for an inexpensive, robust, and rapid discrimination between BSE and scrapie constitutes a topical challenge in the surveillance of ovine TSEs addressed in a variety of studies (8Baron T.G. Madec J.Y. Calavas D. J. Clin. Microbiol. 1999; 37: 3701-3704Crossref PubMed Google Scholar, 9Hope J. Wood S.C. Birkett C.R. Chong A. Bruce M.E. Cairns D. Goldmann W. Hunter N. Bostock C.J. J. Gen. Virol. 1999; 80: 1-4Crossref PubMed Scopus (145) Google Scholar). During the past few years, considerable progress has been achieved in this field of TSE research, predominantly by using immunobiochemical techniques (10Kuczius T. Groschup M.H. Mol. Med. 1999; 5: 406-418Crossref PubMed Google Scholar, 11Stack M.J. Chaplin M.J. Clark J. Acta Neuropathol. 2002; 104: 279-286Crossref PubMed Scopus (182) Google Scholar, 12Lezmi S. Martin S. Simon S. Comoy E. Bencsik A. Deslys J.P. Grassi J. Jeffrey M. Baron T. J. 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Therefore, the of the of the prion the secondary structure the of as for the phenotypic characteristics of TSE During the past few it has been that several different TSE strains can be distinguished by immunobiochemical typing of the electrophoretic mobilities and glycosylation characteristics of in the J. Sidle K.C. J. Ironside J. A.F. Nature. PubMed Scopus Google Scholar, P. R. Capellari S. Ghetti B. M. Gambetti P. PubMed Scopus Google Scholar, P. Capellari S. Gambetti P. N. P. T. J. Giese A. Kretzschmar H. Nature. 1997; PubMed Scopus Google Scholar, Chong A. Birkett C.R. Wood S.C. Hope J. Nature. 1997; PubMed Scopus Google Scholar). strains of hamster-adapted transmissible mink encephalopathy and the of PrP27–30 from and by with exhibited different apparent molecular of and J. Virol. PubMed Google Scholar). evidence for the presence of in and most be for by in the of the prion protein that were from with an with these a has further evidence that from and as as from other hamster-adapted TSE strains have in the structure of J. H. D. H. M. Prusiner S.B. Med. PubMed Scopus Google Scholar). Fourier transform-infrared (FT-IR) spectroscopy used to directly the structure of prion with different TSE the were and substantially by that from and in different β-sheet B. G.J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). as as to phenotypic information of TSE agents or mirrored in the secondary structure of FT-IR structural of or PrP27–30, a that in the secondary structure of the protein, as a tool for the molecular typing and differentiation of TSE agents. this the in this to in laboratory animals TSE agents that TSEs and the challenge of distinguishing isolates that can be by the clinical symptoms or neuropathological by the immunobiochemical of For this Syrian were as animals as have the between different TSE strains and and of such isolates in the it is possible to reliably and other TSE agents by FT-IR structural characterization of PrP27–30 from the the on an that FT-IR of PrP27–30 potentially a for the differentiation of TSE agents, those that are or even to by a variety of approaches for strain the animals used in our study have information this may be of a that the rapid and reliable discrimination of strains in nonexperimental TSEs of animals and humans. 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H. and M. in of brain in from a BSE in a from the were between and days to fatal disease with clinical symptoms of transmissible spongiform of brain in from a were hamsters. symptoms between and in For the present all were on the of ME7-H, and 22A-H in our which showed of and days as the of disease, respectively, and on a of with an of in further not of ME7-H, and 22A-H the in our hamsters. were for clinical symptoms and by the of After the were and further as were in for with for to in for and After in an were in from the were and in for The of as (7Fraser H. Dickinson A.G. J. Comp. Pathol. 1973; 83: 29-40Crossref PubMed Scopus (279) Google Scholar). of S. N. W. D. Giese A. Groschup M.H. Kretzschmar H.A. J. Pathol. Full Text Full Text PDF PubMed Scopus Google Scholar) of brain as M. Bruce M. H. Kretzschmar H.A. M. J. Virol. PubMed Scopus Google Scholar). were in for with for to in for and using a brain After in an were in were on and for For to S. N. W. D. Giese A. Groschup M.H. Kretzschmar H.A. J. Pathol. Full Text Full Text PDF PubMed Scopus Google Scholar), were in TBS, with and with in a and for were in in in and with R. M. R. H. J. Virol. PubMed Google After with the secondary for were with and to the The were for using a For brain were in of to with secondary of of brain in TBS, were with of and of and for M. E. S. H. P. P. J. Gen. Virol. PubMed Scopus Google Scholar). The by of in and and for of the to of brain were in a Nature. PubMed Scopus Google Scholar) or in and using the The were with in for and with in bovine in After in and for with the secondary in bovine in a for used After the in TBS, to using a of and as The of and in each were by for a of the glycosylation were in for each with from four animals with 22A-H, and the of to Different of brain in from with the four different TSE strains the of were in to of and were with as a of for After the by and for were to and with as FT-IR of and prion protein PrP27–30 from the of Syrian the of disease, using a by H. M. M. Simon D. I. M. Ironside J.W. 1997; PubMed Scopus Google Scholar) with some were used of as each of the that required of new were used of by in of in to of the protein with from the The in of to with and and and of brain and in a using a for The and the protein were For of the protein were with of and for The protein by with as M. E. S. H. P. P. J. Gen. Virol. PubMed Scopus Google Scholar). The of the protein by and as M. E. S. H. P. P. J. Gen. Virol. PubMed Scopus Google Scholar), and PrP27–30 also by using as The of protein in the in the of FT-IR of PrP27–30 were with a FT-IR applied for a and a of used an of For each spectrum were and FT-IR were and between and the with to The FT-IR were in the of an FT-IR with a For FT-IR of in the protein from and using a for in of in to a protein to of from the of the were used to for from the protein The of PrP27–30 were from in with a of were to an from in one of which a with a PrP27–30 from of ME7-H, 22A-H, and were each For and the were between and to of the were using a the study on approaches for the characterization and discrimination of TSE agents in would also be for a strain differentiation field such as the or techniques such as strain typing by lesion in mice (7Fraser H. Dickinson A.G. J. Comp. Pathol. 1973; 83: 29-40Crossref PubMed Scopus (279) Google Scholar, M.E. Med. PubMed Scopus Google Scholar) as and the for and with scrapie showed and of animals were and in by and which and and from a animals challenged with or 22A-H scrapie agent exhibited with and scrapie and animals were and not by or and to from a of or as in scrapie were not but the animals showed of with were also to and in a and However, in to the and apparent to by and as in and 22A-H scrapie, exhibited from a and an to to the which showed of and without the scrapie were to from a and not and and symptoms to scrapie and from each other as as from and However, a discrimination between the latter not clinical the lesion profiles caused by ME7-H, 22A-H, and profiles provide a tool for the typing of TSE strains in mice by the and the of in brain (7Fraser H. Dickinson A.G. J. Comp. Pathol. 1973; 83: 29-40Crossref PubMed Scopus (279) Google Scholar). 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PrP27–30 from and showed or from those for and and and exhibited electrophoretic patterns for all PrP27–30 and immunobiochemical typing of pathological prion protein not to a distinction between and the of to Different the of to by a further for the distinction of TSE agents J.Y. A. A. J. P. Baron T. Virol. 1997; PubMed Scopus Google Scholar, R. 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A for all TSE agents the but the β-sheet for each of the individual isolates for for ME7-H, for and for the β-sheet were in the of and ME7-H, for the is only for the 22A-H, the as a of the β-sheet these that the PrP27–30 from the different TSE agents in β-sheet and respectively, TSE agents (263K, and which to PrP27–30 from and showed also and respectively, which might be attributed to the of β-sheet J. PubMed Scopus Google Scholar, H. PubMed Scopus Google Scholar). strains showed a with which is to D. PubMed Scopus Google Scholar, H. of Scholar). and were for 22A-H and such be in the of and The of this have been to from structure in several H. PubMed Scopus Google Scholar). However, the might also an structure to by between and or by the of to S. J. Chem. PubMed Scopus Google Scholar, D. PubMed Scopus Google Scholar). with the FT-IR in our study secondary structure are not our revealed in the patterns of PrP27–30 from the four passaged TSE agents. evidence that PrP27–30 from and featured in β-sheet and other secondary structure elements and to all passaged TSE agents from each For our typing used different scrapie strains passaged in (263K, 22A-H, and ME7-H) and an of hamster-adapted BSE agent in our Two of the passaged agents, 22A-H and ME7-H, to TSEs with indistinguishable and clinical symptoms, indistinguishable lesion and indistinguishable electrophoretic mobilities or glycosylation patterns of PrP27–30. methods for neuropathological or differentiation, such as analysis of the or typing of pathological prion protein different respectively, were a reliable discrimination between and 22A-H not the latter strains only with to but this would not provide a field in our animals and 22A-H by Fraser H. J. Gen. Virol. PubMed Scopus Google Scholar). 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In his decade-long exploration of female sexuality, Sigmund Freud professed to be on a mission to answer the elusive question: What do women want? Unfortunately, the 19th-century psychiatrist was unable to separate that question from the one he ultimately answered: What do men want women to want? In some sense, Freud's inquiries provide an apt metaphor for the medical profession's stance toward female experience. When confronted with the difference presented by the female body as well as women's unique life experiences, the medical field has responded with approaches that range from bemusement to hostility to intense indifference. Although the pernicious effect of gender bias on healthcare delivery is well-known, less attention has been paid to its secondary effects. Disinterest in or hostility to the female experience leads to an informational vacuum that allows for the development of ideas, theories, and assumptions founded on cognitive bias, rationalization, and wishful thinking rather than empirically-based knowledge. These biases, then, are imported into the legal field where they undergird juridical movements that serve to disadvantage women. This essay explores how, in the medical context, the stunted development of knowledge about women, becomes, in the legal context, a dangerous thing. In examining the interplay between medical and social science information and legal dogma, this essay will discuss how bodies of knowledge are selectively pursued, exploited, or ignored in the service of patriarchal assumptions that achieve expression in legal responses to emerging social dilemmas. Selective information flows between the medical and legal professions result in untoward consequences in a wide variety of settings. Here, we limit our focus to two such untoward consequences. The first part of the essay discusses the impoverished medical discourse on female sexuality and how inattention to female sexual fulfillment has led to legal rules that disproportionately affect women's expression as sexual beings. The second part examines available social science data detailing the distinction between psychological and genetic parenthood and shows how that data has been ignored in favor of judicial presumptions that privilege men and disadvantage women in disputes over frozen embryos. A close look at these contested arenas of sexuality and reproduction demonstrates the difficulty of charting women's progress toward equality. On the surface, in both law and medicine, norms of gender equity command facial allegiance. Medicine disavows its earlier efforts to exclude women from the profession, while law proffers the equal protection doctrine as proof that sexist behavior can be rooted out in a zero-tolerance legal culture. Under the waterline, though, unconscious beliefs and stereotypes hold sway. These unruly currents lead to rationalizations and cognitive errors that elude rigorous examination, but affect women at work, at home, and in the bedroom.
【概要】本研究の大きな目的は, 分権化の一層の促進を目指した近年の日本企業おける組織改革が, 意図する成果を生み出しているのかを明らかにすることにある。本稿ではその予備的調査として, 社内組織構造の改革である社内カンパニー制の導入と財務的業績の関係に焦点を当てた分析を実施した。 1994年から2000年にかけて社内カンパニー制を導入した東証一部上場企業49社をサンプル企業とし, 公表財務データから導かれた2つのROAをパフォーマンス指標として, 社内カンパニー制導入前後の業績の比較・分析を行った。 その結果, 社内カンパニー制導入は企業の業績向上に結びついているとはいえず, むしろ低下させていることが判明した。 ただし, この分析結果にはリサーチ・デザインが影響しており, 組織改革が実際の財務的成果として現れるまでのタイム・ラグを考慮すると, より長期的を分析対象とするならば異なる結果が導かれる可能性があると考えられる。【Abstract】Under the pressure of 10-year long economic decline, Japanese firms are struggling to improve their profitability. As one of the ways to do it, Japanese large firms have begun to reorganize their organizational structure and process. This reorganization includes separating strategic and operational decision-making more clearly, decentralizing more decision-making authority, making divisions more autonomous and self-contained to make a prompt decision in response to market conditions at the divisional level. In this paper, the performance of reorganization is preliminarily analyzed based on the sample of 49 Japanese firms which publicized reorganization during 1994-2000. Two ROA are used as performance measures of reorganization. The results show that organizational performance declines after reorganization, but there is some possibility that a time lag exists between implementation of reorganization and its smooth functioning.
The severe acute respiratory syndrome (SARS) crisis in China revealed not only the failures of the Chinese health-care system but also some fundamental structural deficiencies. A decentralized and fragmented health system, such as the one found in China, is not well-suited to making a rapid and coordinated response to public health emergencies. The commercial orientation of the health sector on the supply-side and lack of health insurance coverage on the demand-side further exacerbate the problems of the under-provision of public services, such as health surveillance and preventive care. For the past 25 years, the Chinese Government has kept economic development at the top of the policy agenda at the expense of public health, especially in terms of access to health care for the 800 million people living in rural areas. A significant increase in government investment in the public health infrastructure, though long overdue, is not sufficient to solve the problems of the health-care system. China needs to reorganize its public health system by strengthening both the vertical and horizontal connections between its various public health organizations. China's recent policy of establishing a matching-fund financed rural health insurance system presents an exciting opportunity to improve people's access to health care.
We present a protocol for verification of ``no such entry'' replies from databases. We introduce a new cryptographic primitive as the underlying structure, the keyed hash tree, which is an extension of Merkle's hash tree. We compare our scheme to Buldas et al.'s Undeniable Attesters and Micali et al.'s Zero Knowledge Sets.
"A silent, and in my opinion revolutionary, reform of the budget, to truly become a management tool and an instrument for short-term economic and social programming." This is how the participatory budget was cataloged by a senior official from the Ministry of Economy and Finance. "They are a disaster, with this spending has been atomized... In addition, the MEF has acted against the law", affirms emphatically and harshly -and as a balance, a year later- the main person in charge of the National Decentralization Council (CND).
This paper concerns redistribution and public good provision in an economic federation with two levels of government: a local government in each locality and a (first mover) central government. Each locality is characterized by two ability-types, and the ability-distribution differs across localities. The central government redistributes via a nonlinear income tax and a lump-sum transfer to each local government, while the local governments use proportional income taxes and provide local public goods. We show how the redistributive role of taxation is combined with a corrective role, and how the central government can implement the second best resource allocation. Copyright 2008 Blackwell Publishing, Inc..
This study aims at assessing the performance of local government in Palestine in regard to fiscal and administrative decentralization. Data was gathered from the Ministry of Local Government, Ministry of Finance and a questionnaire was sent to 12 municipalities' key officials. It was found that the government is organized into the central government headed by the president, the cabinet, the governorates, mayors and village councils. The main functions of the local governments are to provide the necessary needed services. It was found that there is a degree of decentralization in providing the intended services as the functions of each level is clearly defined by the law, even though there is an overlapping amongst these functions due to the current situation instability The study explains several aspects including organization of the local government, decision making process, functional responsibilities, partnership among local government and the performance of these partnerships, employment, training programs, the most urgent issues regarding decentralization process, local government finances, financial standing of municipalities, relationship between central and local governments, and decentralization reforms under preparation, The study ends up with conclusions and recommendations. تهدف هذه الدراسة إلى تقييم أداء الهيئات المحلية في فلسطين فيما يتعلق باللامركزية الإدارية والماليـة. وقد تم جمع البيانات اللازمة للدراسة من وزارة الحكم المحلي ووزارة المالية، إضافة الى استبانة كانت قد أرسلت إلى 12 مسئولاً من مسئولي 12 بلدية. وتبين من البحث أن التنظيم الإداري للحكومة يتكون من الحكومة المركزية والمحافظات والبلديات والمجالس القروية. ووجد أن وظائف الهيئات المحلية تتركز في تقديم الخدمات الأساسية للمواطنين. وتبين أن لدى هذه الهيئات درجة كبيرة من اللامركزية في تقديمها لهذه الخدمات، لأن وظائف هذه الهيئات محددة بشكل واضح في قانون الحكم المحلي الفلسطيني، إلا أن هناك بعض التداخل في بعض الصلاحيات نتيجة للظروف الحالية. وأوضحت الدراسة العديد من القضايا الخاصة باللامركزية المالية والإدارية منها: التنظيم الإداري للهيئات المحلية، وعملية اتخاذ القرارات، والمسئوليات الوظيفية، والتعاون بين الهيئات المحلية في تقديم الخدمات، القوى العاملة في الهيئات المحلية والتدريب والحوافز، والقضايا الملحة فيما يتعلق باللامركزية، وتمويل الهيئات المحلية، والأوضاع المالية لهذه الهيئات وعلاقاتها بالحكومة المركزية، والإصلاحات الجارية الخاصة باللامركزية. وانتهت الدراسة بالخلاصة وعدد من التوصيات.
Decentralization policies are an integrated component of health sector reform in an increasing number of countries. The ability of such policies to improve the health system's quality and efficiency is backed up by limited scientific evidence. This study intends to evaluate the impact of decentralization on a specialized field of disease control (leprosy control) in Colombia and Brazil. It analyses the respective juridical base, epidemiological indicators and local publications. Furthermore, 39 semi-structured interviews with key informants were conducted. In both countries, the devolution of technical responsibility and financial resources to the municipalities was the implemented form of decentralization. Access to preventive and curative health care and the community participation in decision-making improved clearly only in Brazil. The decentralization to private providers in Colombia had dubious effects on service quality in general and still more on public health. The flow of finances (including finance collection through state-owned taxes instead of insurance companies) seemed to be better controlled in Brazil. Leprosy control in Brazil took advantage of the decentralization process; in Colombia, it came close to a collapse.
Japan is stuck between lots of rocks and several hard places. It confronts the escalating costs of the world's most rapid pace of ageing with a low and declining birthrate and virtually no support for mass immigration. Moreover, the country faces these costs while severely handicapped by a public debt 1.5 times its GDP plus dramatic declines in the high rate of savings that has hitherto financed it. In addition to all this, the poorly performing economy is in its fourth year of deflation with little hope of producing a recovery in tax revenues. Indeed, deflation and minimal economic growth have eroded national income- tax revenues to their lowest level since the collapse of the bubble economy.
Support for integrated capacity building focusing on learning support for government organizations, communities, networks and small business is the most important contribution foreigners can make to local development.Excessive equipment and action assistance with minimal learning support, is more likely to create dependence.However learning support without locally financed working resources and improved motivation is hardly effective.Decentralization of authority requires decentralization of skills.Learning support focusing on specialist and management training without integrated courses for all staff limits organizational effectiveness.Aid/ cooperation should be much better integrated.This can only be achieved through deeper dialogue and better strategies.To seek a reasonable future for the region