62 resultados para long-acting b-agonist


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Currently, traditional development issues such as economic stagnation, poverty, hunger, and illness as well as newer challenges like environmental degradation and globalisation demand attention. Sustainable development, including its economic, environmental and social elements, is a key goal of decisionmakers. Optimal economic growth has also been a crucial goal of both development theorists and practitioners. This paper examines the conditions under which optimal growth might be sustainable, by assessing the costs and benefits of growth. Key environmental and social aspects are considered. The Ecol-Opt-Growth-1 model analyses economic–ecological interactions, including resource depletion, pollution, irreversibility, other environmental effects, and uncertainty. It addresses some important issues, including savings, investment, technical progress, substitutability of productive factors, intergenerational efficiency, equity, and policies to make economic growth more sustainable—a basic element of the sustainomics framework. The empirical results support growing concerns that costs of growth may outweigh its benefits, resulting in unsustainability. Basically, in a wide range of circumstances, long term economic growth is unsustainable due to increasing environmental damage. Nevertheless, the model has many options that can be explored by policy makers, to make the development path more sustainable, as advocated by sustainomics. One example suggests that government supported abatement programs are needed to move towards sustainable development, since the model runs without abatement were infeasible. The optimal rate of abatement increases over time. Abatement of pollution is necessary to improve ecosystem viability and increase sustainability. Further research is necessary to seek conditions under which alternative economic growth paths are likely to become sustainable.

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Objectives The multiple mini-interview (MMI) overcomes the limitations of the traditional panel interview by multiple sampling to provide improved objectivity and reliability. Reliability of the MMI is affected by number of stations; however, there are few data reporting the influence of interview duration on MMI outcome and reliability. We aimed to determine whether MMI stations can be shortened without affecting applicant rankings or compromising test reliability.
Methods A total of 175 applicants were interviewed and assessed at 10 8-minute stations. Applicants were scored once after 8 minutes at five control stations and twice after 5 minutes and 8 minutes at five experimental stations. Scores at 5 and 8 minutes were compared using t-tests and correlation coefficients. Rankings of applicants based on 5- and 8-minute scores were compared using Spearman's rank order coefficient. The reliability of the MMI was examined for 5- and 8-minute scores using generalisability theory.
Results Mean scores at 5 minutes were lower than mean scores at 8 minutes. Cumulative scores at 5 minutes were also lower. There were highly significant correlations between 5- and 8-minute scores at all experimental stations (0.82–0.91; P < 0.01) and between the cumulative scores at 5 and 8 minutes (0.92; P < 0.01). There was a strong correlation between applicant rankings based on cumulative 5- and 8-minute scores (Spearman's rank order coefficient 0.92). Reliability was not affected.
Conclusions Reducing the duration of MMI stations from 8 to 5 minutes conserves resources with minimal effect on applicant ranking and test reliability.

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Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-{gamma} (PPAR{gamma}) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR{gamma} agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.

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Background: The observance of regulation has become a fundamental part of life for the conduct of business around the world. Governments and their duly appointed designates, acting in the interest of the collective public, have relied on regulation to moderate economic and social behaviour through the imposition and enforcement of rules. While it can be commonly accepted that such a prescriptive framework may be necessary for the achievement of desired economic and social outcomes, regulation does impose costs on society and on individual firms. These costs, which can include the costs for government departments to administer, the cost for firms to comply, and the multitude of indirect costs such as lost innovation and productivity or their interrelated opportunity costs, have received ample attention.

Accountants are key advisers to all businesses on all aspects of doing business, including regulation. As such, it is appropriate that ACCA has sponsored this study, which explores the regulatory issues facing SMEs and the critical role that accountants and other organisations play in helping SMEs be aware of, comply with and generally manage effectively the regulations that apply to their business.

ACCA has consistently argued for a balanced view to be taken on regulation, recognising that certain rules are necessary for the fair development of business and for employees’ rights. Yet at the same time, ACCA recognises that SMEs are likely to be disproportionately burdened by regulatory requirements and, as a consequence, it actively campaigns for fairness in regulation, recognising the issue as a significant factor in the success, productivity and growth of small businesses.

Overview: This study complements similar research commissioned by ACCA in the United Kingdom and Canada (Blackburn et al. 2006), with the aim of helping to provide a more international picture of the effects of regulation on adviceseeking by SMEs and how accountants can help SMEs meet their regulatory obligations.

The research commenced in November 2006 and was conducted over the Australian summer period 2006/7, among SMEs and accounting practices, as follows:

* telephone survey among 250 SMEs
* postal survey among 130 accounting practitioner firms.

Key findings: The SME section of this study revealed the following points.

* Most SMEs (between 70% and 80%), agreed that the regulations under review were reasonable, however there were significantly high levels of concern regarding:
* the number of regulations affecting their business (80%)
* staying up to date with changing regulations (80%)
* complexity of regulation or the ease of understanding regulations (77%)
* inequity, or the cost of regulation in proportion to the business (66%)
* duplication, or being required to provide the same information to more than one government department (55%).
* External accountants were the most common source of advice, being used by 72% of SMEs; this was followed by federal government agencies,    62%; trade or industry bodies, 61%; and a lawyer or solicitor, 53%.
* Highest levels of satisfaction with the advice provided were recorded for lawyers/solicitors (94%), banks (91%) and external accountants (90%).
* Overall, 80% of SMEs who had used accountants rated their service as excellent or good. Thirty per cent gave accountants an excellent rating.
* Accountants rated particularly well on the following attributes:
* the potential for a long-term relationship with the business (81% excellent/good)
* technical understanding of the regulatory requirements that apply to the business (79%)
* ability to meet the needs of the business (77%)
* understanding of the business of the SME and its operations (73%).

The survey of accounting practitioners produced the following information.
* The results indicate that SME firms with fewer than 10 employees are the main source of revenue for the respondent accounting practitioners.
* Virtually all accountants provide regulatory advice, primarily in the areas of taxation (particularly Goods and Services Tax, GST), and Do-It-      Yourself (DIY) superannuation requirements. These services provided the accountants with their largest business growth in the two years before the time of the survey.

Seventy-nine per cent of accountants referred their SME clients to external professional advisers. Their comments indicate (see Appendix 4) that some accountants consider their role to be as convenors or advisers for their SME clients. Importantly, according to the accountants, SME firms with fewer than 10 employees did not update their knowledge of regulatory requirements; they relied on their accountant for the right advice. The main types of external adviser to whom accountants referred their SME clients were lawyers and financial planners.

* Accountants expressed their concern regarding the complexity and amount of regulations affecting their SME clients.
* The accountants also stated that they would like to provide additional advice to their SME clients.
 
Confidence intervals – SME surve
y:  The survey sample size was 250 SMEs from the total of 1.2 million Australian SMEs. Any estimate of proportions agreeing or disagreeing with particular statements must be considered with respect to the margin of possible statistical error. Owing to the small sample size, generalising the results from this study to a wider population of SMEs may be constrained.

A 95% confidence interval of the sample mean for the following estimates based on a percentage agreement of 75% to a proposition with a sample size of 250 would be from 69.5% to 80.5%. The 95% confidence interval for estimates of any other value will diverge slightly in magnitude from the numbers given.

In general then we can be highly confident that the actual sample mean will be within approximately ± 5% of the figure given, with a survey of this size. Confidence intervals – acounting practitioner survey IBISWorld estimates reveal a figure of 9,222 accounting practices in Australia as at June 2006 (IBISWorld 2007). The sample size of 133 accounting practitioners gives a 95% confidence limit that the results reported from the mail-out survey are within the ± 5% confidence interval of the reported values.

Conclusions:  This report describes the results of two parallel surveys undertaken on the impact of business regulation on small and medium-sized enterprises in Australia and on the perceptions of accounting firms about the ways in which the regulatory impact on the SME sector drove their business.

The survey of SMEs provides empirical support for many of the concerns raised with the Regulation Taskforce, which reported to the Australian government in 2006. Many businesses are concerned about the volume and complexity of government legislation as it applies to their business. They are concerned that they are unable to keep up with new legislation and that there is apparent duplication of reporting requirements across the various tiers of government.

The survey of accountants revealed that accounting firms derive a significant proportion of their revenue from SMEs. While the SMEs are concerned with regulatory changes, the accountants surveyed reported that the major growth areas in their businesses were in what could be seen as traditional accounting areas of tax and superannuation. Some SMEs sought advice on areas such as employment law, environmental regulation and health and safety but it appears that many accountants refer their clients to specialists in these areas. Recent changes to the laws regarding financial planning in Australia may lead to changes in the market for financial advice in Australia, with many accountants apparently regarding this as a key driver of future business opportunities.

The surveys were conducted using a similar instrument to similar surveys conducted in the UK and Canada and reported in Blackburn et al. (2006). Comparisons of the Australian survey results with those from the UK and Canada seem to support the perception that Australian business is not over-regulated, but the SME sector is concerned with the volume and complexity of regulation. This suggests that the SME sector wants to see improvements to Australia’s regulatory regime as a result of the work of the Regulation Taskforce undertaken in 2005/6. In its response to the work of the Taskforce the government agreed with 158 of the 178 specific recommendations of the Taskforce. This now needs to be followed through at all levels of government.

Accountants in all three countries understand their SME clients’ concerns with the burden of regulation and they are prepared to advise their clients where appropriate or refer them to specialist advisers. Most business growth for accountants has come from the taxation area. Very few accountants in the UK or Australia specialise in providing advice in the areas of environmental regulation or health and safety regulation.

International comparisons show that in all three countries accountants are generally highly regarded by SMEs for their professionalism and competence. The major area of client concern is the value for money offered by the accountant’s service. In an era of rapidly shifting professional and technical boundaries, accountants need to be more strongly attuned to levels of client satisfaction. Lawyers, financial planners and a plethora of specialist advisers operate in the business services market and if they have an opportunity to take business from accountants by competing on price they may well do so. This suggests a stronger role for professional accounting bodies in monitoring the broader business services market for opportunities and threats on behalf of their membership.

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Objective: This study assesses the long-term cost-effectiveness of a comprehensive model of mental health care for first-episode psychosis. The study is an extension of a previous economic evaluation of the Early Psychosis Prevention and Intervention Centre (EPPIC) that assessed the first-year costs and outcomes of treatment.

Method: The current study used a matched, historical control group design with a follow-up of approximately 8 years. Complete follow-up data were available for 65 of the original 102 participants. Direct public mental health service costs incurred subsequent to the first year of treatment and symptomatic and functional outcomes of 32 participants initially treated for up to 2 years at EPPIC were compared with a matched cohort of 33 participants initially treated by generic mental health services. Treatment-related resource use was measured and valued using Australian published prices.

Results: Almost 8 years after initial treatment, EPPIC subjects displayed lower levels of positive psychotic symptoms (P = .007), were more likely to be in remission (P = .008), and had a more favorable course of illness (P = .011) than the controls. Fifty-six percent of the EPPIC cohort were in paid employment over the last 2 years compared with 33% of controls (P = .083). Each EPPIC patient costs on average A$3445 per annum to treat compared with controls, who each costs A$9503 per annum.

Conclusions: Specialized early psychosis programs can deliver a higher recovery rate at one-third the cost of standard public mental health services. Residual methodological limitations and limited sample size indicate that further research is required to verify this finding.

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Background/Objectives:
Some epidemiological and clinical studies have shown that increased dairy consumption or calcium and/or vitamin D supplementation can have a beneficial effect on blood pressure, and lipid and lipoprotein concentrations. The aim of this study was to assess the long-term effects of calcium-vitamin D3 fortified milk on blood pressure and lipid-lipoprotein concentrations in community-dwelling older men.

Subjects/Methods:
This is a substudy of a 2-year randomized controlled trial in which 167 men aged >50 years were assigned to receive either 400 ml per day of reduced fat (approx1%) milk fortified with approximately 1000 mg of calcium and 800 IU of vitamin D3 or to a control group receiving no additional fortified milk. Weight, blood pressure, lipid and lipoprotein concentrations were measured every 6 months. Participants on lipid-lowering (n=32) or antihypertensive medication (n=39) were included, but those who commenced, increased or decreased their medication throughout the intervention were excluded (n=27).

Results:
In the 140 men included in this study (milk, n=73; control, n=67), there were no significant effects of the calcium-vitamin D3 fortified milk on weight, systolic or diastolic blood pressure, total cholesterol, high-density lipoprotein or low-density lipoprotein cholesterol or triglyceride concentrations at any time throughout the intervention. Similar results were observed after excluding men taking antihypertensive or lipid-lowering medication or limiting the analysis to those with baseline calcium intakes <1000 mg per day and/or with hypovitaminosis D (25(OH)D <75 nmol/l).

Conclusions:
Supplementation with reduced-fat calcium-vitamin D3 fortified milk did not have a beneficial (nor detrimental) effect on blood pressure, lipid or lipoprotein concentrations in healthy community-dwelling older men.

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In this paper, we consider daily financial data of a collection of different stock market indices, exchange rates, and interest rates, and we analyze their multi-scaling properties by estimating a simple specification of the Markov-switching multifractal (MSM) model. In order to see how well the estimated model captures the temporal dependence of the data, we estimate and compare the scaling exponents H(q) (for q=1,2) for both empirical data and simulated data of the MSM model. In most cases the multifractal model appears to generate ‘apparent’ long memory in agreement with the empirical scaling laws.

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Background: Low glycemic index (GI) carbohydrates have been linked to increased satiety. The drive to eat may be mediated by postprandial changes in glucose, insulin and gut peptides.
Objective
: To investigate the effect of a low and a high GI diet on day-long (10 h) blood concentrations of glucose, insulin, cholecystokinin (CCK) and ghrelin (GHR).
Design: Subjects (n¼12) consumed a high and a low GI diet in a randomized, crossover design, consisting of four meals that were matched for macronutrients and fibre, and differed only in carbohydrate quality (GI). Blood was sampled every 30–60 min and assayed for glucose, insulin, CCK and GHR.
Results: The high GI diet resulted in significantly higher glucose and insulin mean incremental areas under the curve (IAUC, P¼0.027 and P¼0.001 respectively). CCK concentration was 59% higher during the first 7 h of the low GI diet (394±95 pmol/l min) vs the high GI diet (163±38 pmol/l min, P¼0.046), but there was no difference over 10 h (P¼0.224). GHR concentration was inversely correlated with insulin concentration (Pearson correlation 0.48, P¼0.007), but did not differ significantly between the low and high GI diets.
Conclusions: Mixed meals of lower GI are associated with lower day-long concentrations of glucose and insulin, and higher CCK after breakfast, morning tea and lunch. This metabolic profile could mediate differences in satiety and hunger seen in some, but not all, studies.

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Creatine monohydrate (CrM) supplementation appears to be relatively safe based on data from short-term and intermediate-term human studies and results from several therapeutic trials. The purpose of the current study was to characterize pathological changes after intermediate-term and long-term CrM supplementation in mice [healthy control and SOD1 (G93A) transgenic] and rats (prednisolone and nonprednisolone treated). Histological assessment (18-20 organs/tissues) was performed on G93A mice after 159 days, and in Sprague-Dawley rats after 365 days, of CrM supplementation (2% wt/wt) compared with control feed. Liver histology was also evaluated in CD-1 mice after 300 days of low-dose CrM supplementation (0.025 and 0.05 g · kg-1 · day-1) and in Sprague-Dawley rats after 52 days of CrM supplementation (2% wt/wt) with and without prednisolone. Areas of hepatitis were observed in the livers of the CrM-supplemented G93A mice (P < 0.05), with no significant inflammatory lesions in any of the other 18-20 tissues/organs that were evaluated. The CD-1 mice also showed significant hepatic inflammatory lesions (P < 0.05), yet there was no negative effect of CrM on liver histology in the Sprague-Dawley rats after intermediate-term or long-term supplementation nor was inflammation seen in any other tissues/organs (P = not significant). Dietary CrM supplementation can induce inflammatory changes in the liver of mice, but not rats. The observed inflammatory changes in the murine liver must be considered in the evaluation of hepatic metabolism in CrM-supplemented mice. Species differences must be considered in the evaluation of toxicological and physiological studies.

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Purpose: Findings recently have shown coupling protein-3 (UCP3) content to be decreased in the skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Uncoupling protein-3 mRNA exists as two isoforms: long (UCP3L) and short (UCP3S). The UCP3 protein is expressed the least in oxidative and the most in glycolytic muscle fibers. Levels of UCP3 have been associated positively with intramyocellular triglyceride (IMTG) contents in conditions of altered fatty acid metabolism. As a source for muscle free fatty acid metabolism, IMTG is decreased in COPD. The current study completely characterized all the parameters of UCP3 expression (ie, UCP3L and UCP3S mRNA expression in whole muscle samples) and UCP3 protein content as well as IMTG content in the different fiber types in patients with COPD and healthy control subjects.

Methods: Using real-time polymerase chain reaction, UCP3 gene expression was quantified. Skeletal muscle fiber type and UCP3 protein and IMTG content were measured using immunofluorescence and Oil red oil staining, respectively.

Results: The findings showed that UCP3L mRNA expression was 44% lower (P < .005) in the patients with COPD than in the control subjects, whereas the UCP3S mRNA content was similar in the two groups. As compared with control subjects, UCP3 protein content was decreased by 89% and 83% and the IMTG content by 64% and 54%, respectively, in types I and IIa fibers (P < .0167) of patients with COPD, whereas they were unchanged in IIx fibers.

Conclusions: The reduced UCP3 and IMTG content in the more oxidative fibers may be linked to the altered muscle fatty acid metabolism associated with COPD. Further studies are required to determine the exact role and clinical relevance of the reduced UCP3 content in patients with COPD.

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Purpose – This paper aims to provide an invaluable insight into long-term forecasting of demand for aged care facilities. This will ensure the provision of adequate supply by government bodies, stakeholders and developers in order to meet the anticipated level of demand, without creating an over-supply or an under-supply scenario.

Design/methodology/approach – Using an innovative approach, different data sources were collectively used to forecast separate individual supply and demand levels, which were then examined together in order to measure the difference between the two variables between 2009-2020. A case study approach was used for Victoria, Australia.

Findings – The paper finds that, although there is excess supply between 2009-2010 and 2019-2020, the period between 2010 and 2019 will experience an under-supply period which cannot be easily rectified over the short term.

Research limitations/implications –
The case study was limited to residential care facilities in Victoria, Australia, although some countries have substantially different age profiles and accommodation supply for older residents. Forecasts are based on information sources from various data suppliers and collectively analysed.

Practical implications – The results are also of direct interest to place managers and planning authorities who are charged with providing medium- and long-term visions and plans for specific locations. This type of research is essential when planning for the eventual aging of the population, where the methodology can be replicated in different areas. Most importantly, this research approach provides a solid basis for decisions regarding the supply of residential aged care facilities as opposed to a simple estimate.

Originality/value – The study adopted a unique approach to analysing the individual supply and demand components for aged care facilities over the long term. This approach is able to accurately determine when there will be an under-supply or over-supply situation and thus provide the opportunity to address the difference before it occurs. This will allow informed decisions about planning aged care facilities in the future to be made as required.

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Background: The organizational context in which healthcare is delivered is thought to play an important role in mediating the use of knowledge in practice. Additionally, a number of potentially modifiable contextual factors have been shown to make an organizational context more amenable to change. However, understanding of how these factors operate to influence organizational context and knowledge use remains limited. In particular, research to understand knowledge translation in the long-term care setting is scarce. Further research is therefore required to provide robust explanations of the characteristics of organizational context in relation to knowledge use.
Aim: To develop a robust explanation of the way organizational context mediates the use of knowledge in practice in long-term care facilities.
Design: This is longitudinal, in-depth qualitative case study research using exploratory and interpretive methods to explore the role of organizational context in influencing knowledge translation. The study will be conducted in two phases. In phase one, comprehensive case studies will be conducted in three facilities. Following data analysis and proposition development, phase two will continue with focused case studies to elaborate emerging themes and theory. Study sites will be purposively selected. In both phases, data will be collected using a variety of approaches, including non-participant observation, key informant interviews, family perspectives, focus groups, and documentary evidence (including, but not limited to, policies, notices, and photographs of physical resources). Data analysis will comprise an iterative process of identifying convergent evidence within each case study and then examining and comparing the evidence across multiple case studies to draw conclusions from the study as a whole. Additionally, findings that emerge through this project will be compared and considered alongside those that are emerging from project one. In this way, pattern matching based on explanation building will be used to frame the analysis and develop an explanation of organizational context and knowledge use over time. An improved understanding of the contextual factors that mediate knowledge use will inform future development and testing of interventions to enhance knowledge use, with the ultimate aim of improving the outcomes for residents in long-term care settings.

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Objectives: To establish natural seroconversion rates and incidence of hepatic pathology in perinatally infected hepatitis B carriers.

Methods: Seventy three perinatally infected hepatitis B carriers identified through maternal screening were evaluated. Fifty three were born to parents from the Indian subcontinent, nine were Oriental, six were Afro-Caribbean, and five were white. Median follow up was 10.24 (range 2.02–20.16) years.

Results: Only three of the children followed up had cleared hepatitis B surface antigen during this period, and 30% of the children had seroconverted to anti-HBe. Seroconversions to anti-HBe were observed in Asian (18/50) and white (4/5) children, but not in Oriental or Afro-Caribbean children. More girls (40%) than boys (23%) had seroconverted, but the difference was not significant. All children were asymptomatic with normal physical examination, growth, and development. Almost half (48%) of the hepatitis B e antigen (HBeAg) positive children had normal hepatic transaminases and liver function. Thirty five liver biopsies were performed in children with active virus replication (HBeAg or hepatitis B virus DNA positive) who were being considered for antiviral treatment as part of a clinical trial and were scored using the Ishak method. Two thirds (62%) of the children had mild hepatitis, 60% had mild fibrosis, and 18% had moderate to severe fibrosis. There was a weak correlation between histological evidence of hepatitis and hepatic transaminase activity, implying that biochemical monitoring of hepatic disease activity may be ineffective.

Conclusions: These asymptomatic hepatitis B virus carrier children remain infectious in the medium to long term with notable liver pathology. They should receive antiviral treatment to reduce infectivity and to prevent further progression of liver disease. Hepatic transaminases alone are not a reliable marker of liver pathology, and liver histology is essential before consideration for antiviral treatment.

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Despite decades of work, an effective HIV vaccine remains elusive. In an effort to elicit protective immunity, investigators have sought to define vaccines able to elicit durable HIV-specific B-cell and T-cell activities. Additionally, vaccines are sought which can induce antibodies of a variety of isotypes, as each isotype possesses unique attributes in terms of opsonization, Fc receptor binding capacity, complement fixation and location. One prominent new vaccine strategy, applied to numerous distinct antigenic systems is the prime boost-regimen, with DNA, vaccinia virus (VV), and/or purified recombinant protein. To examine the durability, location and isotype distribution of responses induced by prime-boost regimens, we tested successive immunizations with DNA, VV and protein (D-V-P), comparing three forms of protein inoculations: (i) purified protein administered intramuscularly with complete Freunds adjuvant, (ii) purified protein administered intranasally, and (iii) purified protein conjugated to oxidized mannan, administered intranasally. We found that all three protocols elicited serum antibodies of multiple isotypes, with serum IgA being most prominent among mice immunized with mannan-conjugated protein. All D-V-P protocols, regardless of protein form or route, also elicited antibody responses at mucosal surfaces. In bronchoalveolar lavage, a tendency toward IgA production was again most prominent in mice boosted with the protein–mannan conjugate. Both B-cell and T-cell responses were sustained for more than 1 year post-immunization following each form of vaccination. Contemporaneous with long-lasting serum and mucosal antibodies were antibody forming cells in the bone marrow of primed animals. Results highlight the D-V-P vaccination strategy as a promising approach for attaining durable, multi-isotype B-cell and T-cell activities toward HIV.