Immunization with cocktail of HIV-derived peptides in montanide ISA-51 is immunogenic, but causes sterile abscesses and unacceptable reactogenicity.

BACKGROUND: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). METHODS: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. RESULTS: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. CONCLUSIONS: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000886.

Valuing drinking water provision as an ecosystem service in the neuse river basin

The valuation of ecosystem services such as drinking water provision is of growing national and international interest. The cost of drinking water provision is directly linked to the quality of its raw water input, which is itself affected by upstream land use patterns. This analysis employs the benefit transfer method to quantify the economic benefits of water quality improvements for drinking water production in the Neuse River Basin in North Carolina. Two benefit transfer approaches, value transfer and function transfer, are implemented by combining the results of four previously published studies with data collected from eight Neuse Basin water treatment plants. The mean net present value of the cost reduction estimates for the entire Neuse Basin ranged from $2.7 million to $16.6 million for a 30% improvement in water quality over a 30-year period. The value-transfer approach tended to produce larger expected benefits than the function-transfer approach, but both approaches produced similar results despite the differences in their methodologies, time frames, study sites, and assumptions. © 2010 ASCE.

The Adjuvant Activity and Mechanisms of Action for Mastoparan 7 Peptide After Intranasal Immunization in Mice

No

Immune responses to Bordetella pertussis infection or immunization in 2 months-old infants

info:eu-repo/semantics/nonPublished

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

The forage supply service in the Chaco native forest : an approach to economic analysis

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The forage supply service in the Chaco native forest : an approach to economic analysis

p.37-45

Load sharing in cluster service provision

The factors that are driving the development and use of grids and grid computing, such as size, dynamic features, distribution and heterogeneity, are also pushing to the forefront service quality issues. These include performance, reliability and security. Although grid middleware can address some of these issues on a wider scale, it has also become imperative to ensure adequate service provision at local level. Load sharing in clusters can contribute to the provision of a high quality service, by exploiting both static and dynamic information. This paper is concerned with the presentation of a load sharing scheme, that can satisfy grid computing requirements. It follows a proactive, non preemptive and distributed approach. Load information is gathered continuously before it is needed, and a task is allocated to the most appropriate node for execution. Performance and reliability are enhanced by the decentralised nature of the scheme and the symmetric roles of the nodes. In addition, the scheme exhibits transparency characteristics that facilitate integration with the grid.

Finance for water and sanitation as a public service

Drawing on empirical evidence gathered through the PSIRU database, this contribution aims at addressing the potential of public finance to enhance the provision of water supply and sanitation as a public service. It highlights the problems associated with (and the disappointing results obtained from) resort to Private Sector Participation and private finance, both historically and in the last 15-20 years, in developed and developing countries. It also addresses the advantages of using public finance as a more cost-effective and equitable instrument to achieve developmental objectives such as the expansion of service coverage and development of water and sanitation infrastructure. The potential of public operations in maximising developmental impact from the social, economic and environmental points of view is then explored referring to specific examples from a variety of countries and regions. These include the in-house restructuring of public operations to enhance transparency, accountability and effectiveness, as well as the use of Public-Public Partnerships (PUPs) to build capacity. Attention is devoted to the specific financial requirements of expanding sewerage services at global level to achieve MDGs or broader developmental goals. These requirements are revisited in light of a regional breakdown of coverage gaps, available resources and development aid flows. These findings challenge the established view among international and bilateral agencies that expanding sewerage services in developing countries is excessively costly and should be abandoned as a priority because unaffordable. This contribution draws on a number of PSIRU Reports, and particularly the following. - http://www.psiru.org/reports/2008-03-W-sewers.pdf - http://boell-latinoamerica.org/download_es/agua08_privatizacion_LA_2007.pdf - http://boell-latinoamerica.org/download_es/agua08_agua_un_servicio_publico.pdf - http://www.psiru.org/reports/2006-03-W-investment.pdf All PSIRU Reports are accessible at http://www.psiru.org/publicationsindex.asp.

Ethnic variations in the experiences of mental health service users in England: results of a national patient survey programme

Background: Minority ethnic groups in the UK are reported to have a poor experience of mental health services, but comparative information is scarce. Aims: To examine ethnic differences in patients’ experience of community mental health services. Method: Trusts providing mental health services in England conducted surveys in 2004 and 2005 of users of community mental health services. Multiple regression was used to examine ethnic differences in responses. Results: About 27 000 patients responded to each of the surveys, of whom 10% were of minority ethnic origin. In the 2004 survey, age, living alone, the 2004 survey, age, living alone, detention and hospital admissions were stronger predictors of patient experience than ethnicity. Self-reported mental health status had the strongest explanatory effect. In the 2005 survey, the main negative differences relative to the White British were for Asians. Conclusions: Ethnicity had a smaller effect on patient experience than other variables. Relative to the White British, the Black group did not report negative experiences whereas the Asian group were most likely to respond negatively. However, there is a need for improvements in services for minority ethnic groups, including access to talking therapies and better recording of ethnicity.

An evaluation of a community matron service from the patients’ perspective

Community matrons are a relatively new government initiative aimed at case managing people with long-term conditions to reduce the number of emergency bed days used in hospitals. Although there have been extensive evaluations of similar case management projects, to date there has been little evaluation of the community matron's role and the perceptions patients have of this new service. One of the main Government agendas for care is to deliver a high quality service driven by the needs of the service users (DH, 2000). In order to drive this agenda, care is to deliver a high quality service driven by the needs of the service users (DH, 2000). In order to drive this agenda, it is important that the views and perceptions of people on the receiving end of the services are heard, valued and appropriate actions taken. This two part evaluative report sets out to explore how people with long-term conditions perceive the impact of community matrons and the differences this new service may have had on their lives. Questionnaires were sent to 100 patients who were currently being case-managed by a community matron to evaluate the community matron service from the patients' perspective. Part two reports on patients' perceptions of the community matron role and the influences of the role on their health.

A life cycle model for product-service systems design

Western manufacturing companies are developing innovative ways of delivering value that competes with the low cost paradigm. One such strategy is to deliver not only products, but systems that are closely aligned with the customer value proposition. These systems are comprised of integrated products and services, and are referred to as Product-Service Systems (PSS). A key challenge in PSS is supporting the design activity. In one sense, PSS design is a further extension of concurrent engineering that requires front-end input from the additional downstream sources of product service and maintenance. However, simply developing products and service packages is not sufficient: the new design challenge is the integrated system. This paper describes the development of a PSS data structure that can support this integrated design activity. The data structure is implemented in a knowledge base using the Protégé knowledge base editor.

Key service issues in two UK manufacturing companies from a PSS perspective

This paper illustrates the key service issues within two UK manufacturing companies,which belong to two different industrial domains, and highlights the main points of difference. It draws also on the literature of Product-Service Systems regarding their definition, types, benefits and difficulties in their implementation

University education as a public service

There is no tradition of public service in large parts of English higher education. This is because historically HE in England has seen itself as independent of the state and unaccountable to the public for its twin roles of research and teaching. These serve its own interests conceived as advancing knowledge and ensuring the continued transmission of that knowledge to future generations. The dominance of this conception explains the so-called ‘academic community’s’ Gaderene rush to abandon free HE in England. Resistance to preserve and extend public service HE will therefore predictably come mainly from former-local authority further and higher education institutions.