Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens

This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)-the causative agents of rheumatic fever and subsequent rheumatic heart disease-was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.

Self-reported difficulty in conceiving as a measure of infertility

BACKGROUND: This study aimed to explore the meaning and potential use of women's self-reported difficulties in conceiving as a measure of infertility in epidemiological studies, and to compare women's stated reasons for infertility with information in their medical records. METHODS: Data were available from a population-based case-control study of ovarian cancer involving 1638 women. The sensitivity and specificity of women's self-reported infertility were calculated against their estimated fertility status based on detailed reproductive histories. Self-reported reasons for infertility were compared with diagnoses documented in women's medical records. RESULTS: The sensitivity of women's self-reported difficulty in conceiving was 66 and 69% respectively when compared with calendar-derived and self-reported times taken trying to conceive; its specificity was 95%. Forty-one (23%) of the 179 women for whom medical records were available had their self-reported fertility problem confirmed. Self-reported infertility causes could be compared with diagnoses in medical records for only 22 of these women. CONCLUSIONS: Self-reported difficulty conceiving is a useful measure of infertility for quantifying the burden of fertility problems experienced in the community. Validation of reasons for infertility is unlikely to be feasible through examination of medical records. Improved education of the public regarding the availability and success rates of infertility treatments is proposed.

A potential role for isothermal calorimetry in studies of the effects of thermodynamic non-ideality in enzyme-catalyzed reactions

Attention is drawn to the feasibility of using isothermal calorimetry for the characterization of enzyme reactions under conditions bearing greater relevance to the crowded biological environment, where kinetic parameters are likely to differ significantly from those obtained by classical enzyme kinetic studies in dilute solution. An outline of the application of isothermal calorimetry to the determination of enzyme kinetic parameters is followed by considerations of the nature and consequences of crowding effects in enzyme catalysis. Some of those effects of thermodynamic non-ideality are then illustrated by means of experimental results from calorimetric studies of the effect of molecular crowding on the kinetics of catalysis by rabbit muscle pyruvate kinase. This review concludes with a discussion of the potential of isothermal calorimetry for the experimental determination of kinetic parameters for enzymes either in biological environments or at least in media that should provide reasonable approximations of the crowded conditions encountered in vivo. Copyright (C) 2004 John Wiley Sons, Ltd.

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.

Protection against group A streptococcal infection by vaccination with self-adjuvanting lipid core M protein peptides

We have investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting group A streptococcal (GAS) vaccine delivery approach. LCP constructs were synthesised incorporating peptides from the M protein conserved carboxy terminal C-repeat region, the amino terminal type-specific region and from both of these regions. Immunisation with the constructs without adjuvant led to the induction of peptide-specific serum IgG antibody responses, heterologous opsonic antibodies, and complete protection from GAS infection. These data indicate that protective immunity to GAS infection can be evoked using the self-adjuvanting LCP system, and point to the potential application of this system in human mucosal GAS vaccine development. (c) 2005 Elsevier Ltd. All rights reserved.

Exploring the potential of xenobiotic-metabolising enzymes as biocatalysts: Evolving designer catalysts from polyfunctional cytochrome P450 enzymes

1. Biological catalysts have the advantage of being able to catalyse chemical reactions with an often exquisite degree of regio- and stereospecificity in contrast with traditional methods of organic synthesis. 2. The cytochrome P450 enzymes involved in human drug metabolism are ideal starting materials for the development of designer biocatalysts by virtue of their catalytic versatility and extreme substrate diversity. Applications can be envisaged in fine chemical synthesis, such as in the pharmaceutical industry and bioremediation. 3. A variety of techniques of enzyme engineering are currently being applied to P450 enzymes to explore their catalytic potential. Although most studies to date have been performed with bacterial P450s, reports are now emerging of work with mammalian forms of the enzymes. 4. The present minireview will explore the rationale and general techniques for redesigning P450s, review the results obtained to date with xenobiotic-metabolising forms and discuss strategies to overcome some of the logistic problems limiting the full exploitation of these enzymes as industrial-scale biocatalysts.

Relations between companion animals and self-reported health in older women: Cause, effect or artifact

A large longitudinal dataset on women's health in Australia provided the basis of analysis of potential positive health effects of living with a companion animal. Age, living arrangements, and housing all strongly related to both living with companion animals and health. Methodological problems in using data from observational studies to disentangle a potential association in the presence of substantial effects of demographic characteristics are highlighted. Our findings may help to explain some inconsistencies and contradictions in the literature about the health benefits of companion animals, as well as offer suggestions for ways to more forward in future investigations of human-pet relationships.

Drinking refusal self-efficacy questionnaire-revised (DRSEQ-R): a new factor structure with confirmatory factor analysis

The drinking refusal self-efficacy questionnaire (DRSEQ: Young, R.M., Oei, T.P.S., 1996. Drinking expectancy profile: test manual. Behaviour Research and Therapy Centre, University of Queensland, Australia Young, R.M., Oei, T.P.S., Crook, G.M., 1991. Development of a drinking refusal self-efficacy questionnaire. J. Psychopathol. Behav. Assess., 13, 1-15) assesses a person's belief in their ability to resist alcohol. The DRSEQ is a sound psychometric instrument based on exploratory factor analyses, but has not been subjected to confirmatory factor analysis. In total 2773 participants were used to confirm the factor structure of the DRSEQ. Initial analyses revealed that the original structure was not confirmed in the current study. Subsequent analyses resulted in a revised factor structure (DRSEQ-R) being confirmed in community, student and clinical samples. The DRSEQ-R was also found to have good construct and concurrent validity. The factor structure of the DRSEQ-R is more stable than the original structure of the DRSEQ and the revised scale has considerable potential in future alcohol-related research. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

General self-concept and life satisfaction for boys with differing levels of physical coordination: The role of goal orientations and leisure participation

Participation in leisure-time activities, self-concept perceptions and individual dispositional goal orientations were examined as mediators of relationships between physical coordination and self-evaluations of life satisfaction and general self-concept for 173 boys aged 10-13 years. Participants completed seven-day activity diaries and 12-month retrospective recall questionnaires recording participation in leisure-time activities. Self-report measures of self-concept, global life satisfaction and dispositional goal orientations were also completed. Results showed that boys with moderate to severe physical coordination difficulties had significantly lower self-concept perceptions of physical ability and appearance, peer and parent relations and general self-concept, as well as lower life satisfaction than boys with medium to high levels of physical coordination. The relationships between boys' physical coordination and their self-perceptions of life satisfaction and general self-concept were significantly influenced by individual self-concept appraisals of physical ability and appearance, peer and parent relations. Adopting task-oriented goals was found to positively change the relationship between physical coordination and both general self-concept and life satisfaction. Team sport participation positively mediated the relationship between physical coordination and life satisfaction. The potential for team sport participation and adoption of task-oriented goals to influence life satisfaction for boys with differing levels of physical coordination was discussed. (c) 2006 Elsevier B.V.. All rights reserved.

Factor analysis of the self-report Dysexecutive (DEX-S) Questionnaire

The self-rating Dysexecutive Questionnaire (DEX-S) is a recently developed standardized self-report measure of behavioral difficulties associated with executive functioning such as impulsivity, inhibition, control, monitoring, and planning. Few studies have examined its construct validity, particularly for its potential wider use across a variety of clinical and nonclinical populations. This study examines the factor structure of the DEX-S questionnaire using a sample of nonclinical (N = 293) and clinical (N = 49) participants. A series of factor analyses were evaluated to determine the best factor solution for this scale. This was found to be a 4-factor solution with factors best described as inhibition, intention, social regulation, and abstract problem solving. The first 2 factors replicate factors from the 5-factor solutions found in previous studies that examined specific subpopulations. Although further research is needed to evaluate the factor structure within a range of subpopulations, this study supports the view that the DEX has the factor structure sufficient for its use in a wider context than only with neurological or head-injured patients. Overall, a 4-factor solution is recommended as the most stable and parsimonious solution in the wider context.

Bias, precision and heritability of self-reported and clinically measured height in Australian twins

Many studies of quantitative and disease traits in human genetics rely upon self-reported measures. Such measures are based on questionnaires or interviews and are often cheaper and more readily available than alternatives. However, the precision and potential bias cannot usually be assessed. Here we report a detailed quantitative genetic analysis of stature. We characterise the degree of measurement error by utilising a large sample of Australian twin pairs (857 MZ, 815 DZ) with both clinical and self-reported measures of height. Self-report height measurements are shown to be more variable than clinical measures. This has led to lowered estimates of heritability in many previous studies of stature. In our twin sample the heritability estimate for clinical height exceeded 90%. Repeated measures analysis shows that 2-3 times as many self-report measures are required to recover heritability estimates similar to those obtained from clinical measures. Bivariate genetic repeated measures analysis of self-report and clinical height measures showed an additive genetic correlation > 0.98. We show that the accuracy of self-report height is upwardly biased in older individuals and in individuals of short stature. By comparing clinical and self-report measures we also showed that there was a genetic component to females systematically reporting their height incorrectly; this phenomenon appeared to not be present in males. The results from the measurement error analysis were subsequently used to assess the effects of error on the power to detect linkage in a genome scan. Moderate reduction in error (through the use of accurate clinical or multiple self-report measures) increased the effective sample size by 22%; elimination of measurement error led to increases in effective sample size of 41%.

'Occasional' and 'social' smokers: Potential target groups for smoking cessation campaigns?

Objective: To describe the characteristics [of self-described 'occasional' and 'social' Australian smokers. Design: Analysis of a national cross-sectional survey of smoking patterns, conducted in Australia in 2004. Setting and participants: Australian adults in 2004 who responded to a survey question about self-described smoking status. Main outcome measures: Demographic characteristics, patterns of alcohol and tobacco use, smoking cessation attempts in the past year, and interest in cessation. Results: Smokers who described themselves as 'occasional' and 'social' smokers comprised 29% of all smokers. A significant proportion of occasional and social smokers had been daily smokers, but the majority either believed that they had 'already quit' or had no intention of quitting smoking. Conclusions: Self-ascribed occasional and social smokers potentially represent an important target group for cessation. These types of smokers may be more resistant to public health messages regarding cessation because they do not view their smoking behaviour as presenting a high risk.

The application of numerical modelling to the assessment of the potential for, and the detection of, spontaneous combustion in coal mines

Numerical modelling has been used to examine the relationship between the results of two commonly used methods of assessing the propensity of coal to spontaneous combustion, the R70 and Relative Ignition Temperature tests, and the likely behaviour in situ. The criticality of various parameters has been examined and a method of utilising critical self-heating parameters has been developed. This study shows that on their own, the laboratory test results do not provide a reliable guide to in situ behaviour but can be used in combination to considerably increase the ability to predict spontaneous combustion behaviour.

Distance measurement using the change in junction voltage across a laser diode due to the self-mixing effect

Conventional detection scheme for self-mixing sensors uses an integrated photodiode within the laser package to monitor the self mixing signal. This arrangement can be simplified by directly obtaining the self-mixing signals across the laser diode itself and omitting the photodiode. This work reports on a Vertical-Cavity Surface-Emitting Laser (VCSEL) based selfmixing sensor using the laser junction voltage to obtain the selfmixing signal. We show that the same information can be obtained with only minor changes to the extraction circuitry leading to potential cost saving with reductions in component costs and complexity and significant increase in bandwidth favoring high speed modulation. Experiments using both photo current and voltage detection were carried out and the results obtained show good agreement with the theory.