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Little Hope (little + hope)
Selected Abstracts,-Amyloid immunization approaches for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Bruno P. Imbimbo Abstract Alzheimer's disease (AD) represents the third leading cause of death in the U.S. and the leading cause of dementia in the elderly population. Until recently, there was little hope of efficiently combating this devastating disease. The deposition of ,-amyloid (A,) is the major pathological hallmark of AD brains. Genetic, biochemical, and pharmacological evidence support the hypothesis that A, plays a key role in the development of the disease. Thus, in the last 5 years a number of pharmacological strategies have been developed to interfere with the A, cascade. The most revolutionary of these approaches was proposed in 1999 by scientists at Elan Pharmaceuticals, which immunized against A, transgenic mice with spontaneously developing A, pathology. The immunization was achieved by subcutaneous injections of a preaggregated form of the synthetic human 42-amino acid A, emulsified with Freund's adjuvant, an immune stimulant. The vaccination caused a near complete inhibition of A, plaque formation in younger animals and a marked reduction of the A, burden in older animals. The effects on A, plaques were accompanied by a reduction of A,-associated astrogliosis and neuritic dystrophy. These results were later confirmed by other groups with similar vaccination protocols, which also demonstrated that the A, immunization of transgenic animals normalize or reduce the cognitive impairment associated with A, pathology. Interestingly, effective removal of brain A, plaques was also obtained by peripherally administering A, antibodies. The mechanism with which the vaccine increases A, clearance is not fully understood. Centrally, the vaccine appears to activate A, phagocytosis by microglial monocytes. Peripherally, serum A, antibodies bind and sequester A,, thus altering its equilibrium between CNS and plasma. The dramatic results obtained in animal models of AD raised unprecedented hopes for both a preventive and a curative intervention for this devastating disorder. A vaccine preparation for human use (AN-1792) composed of preaggregated human A,42 peptide and a highly purified saponin derivative (QS-21) was developed by Elan Pharmaceuticals and Wyeth Ayerst and tested in AD patients. Unfortunately, a Phase IIa study aimed at evaluating the safety and immunological activity of AN-1792 in 360 AD patients was discontinued because 15 subjects receiving the vaccine developed serious signs of CNS inflammation. Both central activation of cytotoxic T cells and autoimmune reactions were proposed as potential mechanisms of toxicity. Other therapeutic A, vaccination strategies are being pursued, including immuno-conjugates and monoclonal antibodies. The future of these and other A, immunization approaches depend on a clear understanding of the mechanism of A, clearance and additional insight into the role of inflammation in the AD brain. Drug Dev. Res. 56:150,162, 2002. © 2002 Wiley-Liss, Inc. [source] A Serpent in the Garden: Implications of Highway Development in Canada's Niagara Fruit BeltJOURNAL OF HISTORICAL SOCIOLOGY, Issue 4 2002A. Suzanne Hill This paper examines how long,term residents of the Niagara Fruit Belt of Ontario, Canada interpret the disappearance of prime farming land. The Queen Elizabeth Way, a highway development, is identified as one major initiative which has deeply affected the characteristics of the region and, importantly, has overshadowed perspectives of development and growth. An historical account of the development of the highway is presented to show how the event has become symbolic of urbanization and government interference. Participants in the study expressed little hope for the continuation of fruit farming in the region. [source] The experiences of carers in Taiwanese culture who have long-term schizophrenia in their families: a phenomenological studyJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 10 2009X.-Y. HUANG rn msc dnsc Accessible summary ,,Carers in families with long-term schizophrenia in Taiwanese culture are suffering several burdens, such as burdens of caring and emotional burdens. ,,Strategies of coping, cognitive and religious coping strategies were used by carers in order to cope with their burdens. ,,The awareness of such traditional cultural values would help people to provide care in a culturally sensitive manner. Abstract Schizophrenia is a severe illness with little hope of recovery and requires long-term care. The purpose of this study was to explore the experiences of carers who live with someone with long-term schizophrenia, within the cultural context of Taiwan. The study was conducted in a community setting in central Taiwan. A qualitative phenomenological approach was used to explore the experiences of carers. Purposive sampling was used by selecting the carers who were close relatives of the clients, had lived with the clients for at least 1 year and bore most of the responsibilities. Semi-structured face-to-face interviews were conducted to collect the data and narratives were analysed using Colaizzi's (1978) seven-step method. Data saturation was achieved after interviewing 10 carers. Three themes and eight sub-themes were identified: burdens of caring (helping clients' illness, lack of professional support and family conflicts), emotional burdens (sadness, worry and fear) and strategies of coping (cognitive and religious coping strategies). Our study supported the importance for nurses to understand the cultural aspects of mental illness, particularly the widespread cultural beliefs and patterns of help seeking behaviours, in order to provide culturally sensitive health care. [source] Auricular surface aging: Worse than expected?AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2006A test of the revised method on a documented historic skeletal assemblage Abstract This study presents results and recommendations arising from a blind test of the revised age estimation method for the auricular surface as proposed by Buckberry and Chamberlain (2002 Am. J. Phys. Anthropol. 119:321,329). Auricular surfaces of 167 individuals from St. Bride's, London, a documented skeletal assemblage spanning the late 17th to early 19th century, were analyzed for the following traits: transverse organization, surface texture appearance, macroporosity, microporosity, and morphological changes to the apex. Composite scores of trait expressions were found to generally correlate with age and to show a positive association with known chronological age (P < 0.01). However, when composite scores were combined to define auricular surface phases, which ultimately assign age estimations, only three distinct developmental stages, compared with seven suggested by Buckberry and Chamberlain (2002 Am. J. Phys. Anthropol. 119:321,329), could be identified and statistically supported, all showing a considerable degree of individual variation in age. The most well-defined stage in the St. Bride's assemblage was the new stage III, where the majority of individuals were older than 60 years, whereas middle-aged adults displayed a large variation in composite scores. These results provide little hope for a promising application of age-at-death estimation of auricular surface morphology traits with higher resolution, but rather suggest indications of broad stages of life. Am J Phys Anthropol, 2006. © 2006 Wiley-Liss, Inc. [source] ECONOMICS OF THE LIVING DEAD,THE JAPANESE ECONOMIC REVIEW, Issue 1 2006TAKEO HOSHI Zombie firms are those firms that are insolvent and have little hope of recovery but avoid failure thanks to support from their banks. This paper identifies zombie firms in Japan, and compares the characteristics of zombies to other firms. Zombie firms are found to be less profitable, more indebted, more dependent on their main banks, more likely to be found in non-manufacturing industries and more often located outside large metropolitan areas. Overall, larger size makes the firm less likely to be a zombie, but among small firms, relatively larger firms are more likely to be protected and become zombies. Controlling for profitability, the exit probability for zombie firms does not differ from that for non-zombies. Zombie firms tend to increase employment by more (but do not reduce employment by more) than non-zombies. Finally, when the proportion of zombie firms in an industry increases, job creation declines and job destruction increases, and the effects are stronger for non-zombies. [source] Low-Growth Equilibrium Accompanied by High Levels of Educational AttainmentTHE JAPANESE ECONOMIC REVIEW, Issue 4 2002Koichi Yotsuya The paper demonstrates the low-growth trap associated with high educational attainment in an overlapping-generations model by examining the dual positive effect of senior educated workers in leading-edge technology: on technological progress and on young workers' on-the-job learning. If new technology is sufficiently productive, young workers will demand education to update technology when old, and high technological growth is sustained in the future. Conversely, if new technology is unproductive, they will demand education merely to improve the skills necessary for existing technology, and technological progress will stagnate. Nevertheless, vigorous investment in education occurs since young workers have little hope for on-the-job learning. JEL Classification Numbers: I20, J24, O33, O40. [source] Working Under Monarchy: Political Leadership and Democracy in NepalASIAN POLITICS AND POLICY, Issue 1 2009Ina Acharya The purpose of this study was to discover the prospects and challenges of democracy in Nepal. Mired with corruption and escalating conflict, Nepal is in its 16th year of democratic transition, with little hope for a fully functional, consolidated, liberal democracy. In trying to study the causes, the author hypothesizes that political leaders have made decisions that have had an adverse effect on democracy in Nepal. Empirical research has been conducted on landmark decisions made by political leaders to test the hypothesis. The author concludes that charismatic leaders, depending on their vision, statesmanship, and liberalism, choose to decide differently, and these decisions determine their mode of governance and its impact on democracy. [source] | |||||||||||||