Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct

Background & objectives: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved C-region. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach. Methods: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies. Results: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins. Interpretation & conclusion: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.

A comparison of the Yale-Brown obsessive compulsive scale for "Heavy drinking" with a single item craving measure: Construct validity and clinical utility

The measurement of alcohol craving began with single-item scales. Multifactorial scales developed with the intention to capture more fully the phenomenon of craving. This study examines the construct validity of a multifactorial scale, the Yale-Brown Obsessive Compulsive Scale for heavy drinking (Y-BOCS-hd). The study compares its clinical utility with a single item visual-analogue craving scale. The study includes 212 alcohol dependent subjects (127 males, 75 females) undertaking an outpatient treatment program between 1999-2001. Subjects completed the Y-BOCS-hd and a single item visual-analogue scale, in addition to alcohol consumption and dependence severity measures. The Y-BOCS-hd had strong construct validity. Both the visual-analogue alcohol craving scale and Y-BOCS-hd were weakly associated with pretreatment dependence severity. There was a significant association between pretreatment alcohol consumption and the visual-analogue craving scale. Neither craving measure was able to predict total program abstinence or days abstinent. The relationship between obsessive-compulsive behavior in alcohol dependence and craving remains unclear.

Using student feedback to construct an assessment rubric for a concept map in physiology

Constructing quality assessment rubrics can be challenging, especially when they are used for integrated, group-centered, applied learning. We describe a collaborative assessment task in which groups of second-year dentistry students developed a complex concept map. In groups of four, the students were given a written, simulated, medical history of a patient and required to construct a concept map illustrating relevant pathophysiological concepts and pharmacological interventions. This report describes a research project aimed at making educational goals of the task more explicit through investigating student and faculty member understandings of the criteria that might be used to assess the concept map. Information was gathered about the perceptions of students in relation to the learning goals associated with the task. These were compared with faculty member perceptions. The findings were used to develop an assessment rubric intended to be more accessible to learners. The new rubric used the language of both faculty members and students to more clearly represent expectations of each criterion and standard. This assessment rubric will be used in 2005 for the next phase of the project.

Dynamic training volume: A construct of both time under tension and volume load

The purpose of this study was to investigate the effects of three different weight training protocols, that varied in the way training volume was measured, on acute muscular fatigue. Ten resistance-trained males performed all three protocols which involved dynamic constant resistance exercise of the elbow flexors. Protocol A provided a standard for the time the muscle group was under tension (TUT) and volume load (VL), expressed as the product of the total number of repetitions and the load that was lifted. Protocol B involved 40% of the TUT but the same VL compared to protocol A; protocol C was equated with protocol A for TUT but only involved 50% of the VL. Fatigue was assessed by changes in maximum voluntary isometric force and integrated electromyography (iEMG) between the pre- and post-training protocols. The results of the study showed that, when equated for VL, greater TUT produced greater overall muscular fatigue ( p

Using the Amazon metric to construct an image database based on what people do, not what they say

Current image database metadata schemas require users to adopt a specific text-based vocabulary. Text-based metadata is good for searching but not for browsing. Existing image-based search facilities, on the other hand, are highly specialised and so suffer similar problems. Wexelblat's semantic dimensional spatial visualisation schemas go some way towards addressing this problem by making both searching and browsing more accessible to the user in a single interface. But the question of how and what initial metadata to enter a database remains. Different people see different things in an image and will organise a collection in equally diverse ways. However, we can find some similarity across groups of users regardless of their reasoning. For example, a search on Amazon.com returns other products also, based on an averaging of how users navigate the database. In this paper, we report on applying this concept to a set of images for which we have visualised them using traditional methods and the Amazon.com method. We report on the findings of this comparative investigation in a case study setting involving a group of randomly selected participants. We conclude with the recommendation that in combination, the traditional and averaging methods would provide an enhancement to current database visualisation, searching, and browsing facilities.

Refining exceptions using King and Morgan's exit construct

In this paper we discuss the refinement of exceptions. We extend the Guarded Command Language normally used in the refinement calculus, with a simple exception handling statement, which we model using King and Morgan's exit statement (1995). We derive some variants of King and Morgan's refinement laws for their exit statement, and illustrate the approach with an example of a refinement of a simple program.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended.