A role of Hsp60 in autoimmune diabetes: analysis in a transgenic model.

A pathogenic role for self-reactive cells against the stress protein Hsp60 has been proposed as one of the events leading to autoimmune destruction of pancreatic beta cells in the diabetes of nonobese diabetic (NOD) mice. To examine this hypothesis, we generated transgenic NOD mice carrying a murine Hsp60 transgene driven by the H-2E alpha class II promoter. This would be expected to direct expression of the transgene to antigen-presenting cells including those in the thymus and so induce immunological tolerance by deletion. Detailed analysis of Hsp60 expression revealed that the endogenous gene is itself expressed strongly in thymic medullary epithelium (and weakly in cortex) yet fails to induce tolerance. Transgenic mice with retargeted Hsp60 showed overexpression of the gene in thymic cortical epithelium and in bone marrow-derived cells. Analysis of spontaneous T-cell responses to a panel of self and heterologous Hsp60 antigens showed that tolerance to the protein had not been induced, although responses to an immunodominant 437-460 epitope implicated in disease were suppressed, probably indicating an epitope shift. This correlated with changes in disease susceptibility: insulitis in transgenic mice was substantially reduced so that pathology rarely progressed beyond periislet infiltration. This was reflected in a substantial reduction in hyperglycemia and disease. These data indicate that T cells specific for some epitopes of murine Hsp60 are likely to be involved in the islet-cell destruction that occurs in NOD mice.

Role of hydrophobic interactions and desolvation in determining the structural properties of a model alpha beta peptide.

Model AB, a 20-amino acid peptide that was designed to adopt an alpha beta tertiary structure stabilized by hydrophobic interactions between residues in adjacent helical and extended segments, exhibited large pKa shifts of several ionizable groups and slow hydrogen/deuterium exchange rates of nearly all the peptide amide groups [Butcher, D. J., Bruch, M. D. & Moe, G. T. (1995) Biopolymers 36, 109-120]. These properties, which depend on structure and hydration, are commonly observed in larger proteins but are quite unusual for small peptides. To identify which of several possible features of the peptide design are most important in determining these properties, several closely related analogs of Model AB were characterized by CD and NMR spectroscopy. The results show that hydrophobic interactions between adjacent helical and extended segments are structure-determining and have the additional effect of altering water-peptide interactions over much of the peptide surface. These results may have important implications for understanding mechanisms of protein folding and for the design of independently folding peptides.

A review of the driver-vehicle effectiveness (DRIVEM) model. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Effectiveness of alternative skid reduction measures. Volume II: benefit-cost model. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Freedom for individual development : an implementation model for reducing minority and sex role stereotyping /

WI docs. no.: Ed.3/2:9267

The role of gender in the construction and evaluation of feedback effectiveness

This study investigated factors that influence managers’ conceptions and subordinates’ perceptions of effective feedback. A social rules perspective was used to operationalize male and female managers’ conceptions of effective negative feedback. In the first study, 68 male and female managers identified their optimal strategies for providing feedback to subordinates. Male and female managers endorsed different goals and tactics for giving negative feedback, particularly in terms of levels of participation and directness. In the second study, 116 male and female subordinates evaluated the comparative effectiveness and difficulty of these and other standard approaches to feedback. The female manager strategy was evaluated by both men and women as generally more task and relationship effective but not more difficult to enact.

General practitioners' role in preventive medicine: scenario analysis using alcohol as a case study

The purpose of this analysis is threefold: first, to extract from the literature, current levels of GP detection of at-risk drinking by their patients, rates at which general practitioners (GPs) offer an intervention; and the effectiveness of these interventions; secondly, to develop a model based on this literature to be used in conjunction with scenario analysis; and thirdly, to consider the cost implications of current efforts and various scenarios. This study deals specifically with Australian general practice. A two-step procedure is used in the scenario analysis, which involves identifying opportunities for detection, intervention, effectiveness and assigning probabilities to outcomes. The results suggest that increasing rates of GP intervention achieves greatest benefit and return on resource use. For every 5% point increase in the rate of GP intervention, an additional 26 754 at-risk drinkers modify their drinking behaviour at a cost of $231.45 per patient. This compares with a cost per patient modifying drinking behaviour of $232.60 and $208.31 for every 5% point increase in the rates of detection and effectiveness, respectively. The knowledge, skill and attitude of practitioners toward drinking are significant, and they can be the prime motivators in persuading their patients to modify drinking behaviour.

An integrated cognitive model of panic disorder: The role of positive and negative cognitions

One reason for the neglect of the role of positive factors in cognitive-behavioural therapy (CBT) may relate to a failure to develop cognitive models that integrate positive and negative cognitions. Bandura [Psychol. Rev. 84 (1977) 191; Anxiety Res. 1 (1988) 77] proposed that self-efficacy beliefs mediate a range of emotional and behavioural outcomes. However, in panic disorder, cognitively based research to date has largely focused on catastrophic misinterpretation of bodily sensations. Although a number of studies support each of the predictions associated with the account of panic disorder that is based on the role of negative cognitions, a review of the literature indicated that a cognitively based explanation of the disorder may be considerably strengthened by inclusion of positive cognitions that emphasize control or coping. Evidence to support an Integrated Cognitive Model (ICM) of panic disorder was examined and the theoretical implications of this model were discussed in terms of both schema change and compensatory skills accounts of change processes in CBT. (C) 2004 Elsevier Ltd. All rights reserved.

Effectiveness of topical skin care provided in aged care facilities

Background The 2001 Australian census revealed that adults aged 65 years and over constituted 12.6% of the population, up from 12.1% in 1996. It is projected that this figure will rise to 21% or 5.1 million Australians by 2031. In 1998, 6% (134 000) of adults in Australia aged 65 years and over were residing in nursing homes or hostels and this number is also expected to rise. As skin ages, there is a decreased turnover and replacement of epidermal skin cells, a thinning subcutaneous fat layer and a reduced production of protective oils. These changes can affect the normal functions of the skin such as its role as a barrier to irritants and pathogens, temperature and water regulation. Generally, placement in a long-term care facility indicates an inability of the older person to perform all of the activities of daily living such as skin care. Therefore, skin care management protocols should be available to reduce the likelihood of skin irritation and breakdown and ultimately promote comfort of the older person. Objectives The objective of this review was to determine the best available evidence for the effectiveness and safety of topical skin care regimens for older adults residing in long-term aged care facilities. The primary outcome was the incidence of adverse skin conditions with patient satisfaction considered as a secondary outcome. Search strategy A literature search was performed using the following databases: PubMed (NLM) (1966–4/2003), Embase (1966–4/2003), CINAHL (1966–4/2003), Current Contents (1993–4/2003), Cochrane Library (1966–2/2003), Web of Science (1995–12/2002), Science Citation Index Expanded and ProceedingsFirst (1993–12/2002). Health Technology Assessment websites were also searched. No language restrictions were applied. Selection criteria Systematic reviews of randomised controlled trials, randomised and non-randomised controlled trials evaluating any non-medical intervention or program that aimed to maintain or improve the integrity of skin in older adults were considered for inclusion. Participants were 65 years of age or over and residing in an aged care facility, hospital or long-term care in the community. Studies were excluded if they evaluated pressure-relieving techniques for the prevention of skin breakdown. Data collection and analysis Two independent reviewers assessed study eligibility for inclusion. Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data. Results The resulting evidence of the effectiveness of topical skin care interventions was variable and dependent upon the skin condition outcome being assessed. The strongest evidence for maintenance of skin condition in incontinent patients found that disposable bodyworn incontinence protection reduced the odds of deterioration of skin condition compared with non-disposable bodyworns. The best evidence for non-pressure relieving topical skin care interventions on pressure sore formation found the no-rinse cleanser Clinisan to be more effective than soap and water at maintaining healthy skin (no ulcers) in elderly incontinent patients in long-term care. The quality of studies examining the effectiveness of topical skin care interventions on the incidence of skin tears was very poor and inconclusive. Topical skin care for prevention of dermatitis found that Sudocrem could reduce the redness of skin compared with zinc cream if applied regularly after each pad change, but not the number of lesions. Topical skin care on dry skin found the Bag Bath/Travel Bath no-rinse skin care cleanser to be more effective at preventing overall skin dryness and most specifically flaking and scaling when compared with the traditional soap and water washing method in residents of a long-term care facility. Information on the safety of topical skin care interventions is lacking. Therefore, because of the lack of evidence, no recommendation on the safety on any intervention included in this review can be made.

Determinants in the development of advanced nursing practice: a case study of primary-care settings in Hong Kong

Different factors have been shown to influence the development of models of advanced nursing practice (ANP) in primary-care settings. Although ANP is being developed in hospitals in Hong Kong, China, it remains undeveloped in primary care and little is known about the factors determining the development of such a model. The aims of the present study were to investigate the contribution of different models of nursing practice to the care provided in primary-care settings in Hong Kong, and to examine the determinants influencing the development of a model of ANP in such settings. A multiple case study design was selected using both qualitative and quantitative methods of data collection. Sampling methods reflected the population groups and stage of the case study. Sampling included a total population of 41 nurses from whom a secondary volunteer sample was drawn for face-to-face interviews. In each case study, a convenience sample of 70 patients were recruited, from whom 10 were selected purposively for a semi-structured telephone interview. An opportunistic sample of healthcare professionals was also selected. The within-case and cross-case analysis demonstrated four major determinants influencing the development of ANP: (1) current models of nursing practice; (2) the use of skills mix; (3) the perceived contribution of ANP to patient care; and (4) patients' expectations of care. The level of autonomy of individual nurses was considered particularly important. These determinants were used to develop a model of ANP for a primary-care setting. In conclusion, although the findings highlight the complexity determining the development and implementation of ANP in primary care, the proposed model suggests that definitions of advanced practice are appropriate to a range of practice models and cultural settings. However, the findings highlight the importance of assessing the effectiveness of such models in terms of cost and long-term patient outcomes.

Why do people engage in collective action? Revisiting the role of perceived effectiveness

Research has shown limited support for the notion that perceived effectiveness of collective action is a predictor of intentions to engage in collective action. One reason may be that effectiveness has been in terms of whether the action will influence key decision makers. We argue that the effectiveness of collective action might be judged by other criteria, such as whether it influences third parties, builds an oppositional movement, and expresses values. Two hundred and thirty one attendees at a rally rated the effectiveness of the rally and their intentions to engage in future collective action. For those participants who were not members of an organization, intentions were linked to the perceived effectiveness of the rally in expressing values and influencing the public. For those who were members of an organization, intentions were linked only to the effectiveness of the rally in building an oppositional movement.