A multi-vector, multi-envelope HIV-1 vaccine

The St. Jude Children's Research Hospital (St. Jude) HIV-1 vaccine program is based on the observation that multiple, antigenically distinct HIV-1 envelope protein structures are capable of mediating HIV-1 infection. A cocktail vaccine comprising representatives of these diverse structures (immunotypes) is therefore considered necessary to elicit lymphocyte populations that prevent HIV-1 infection. This strategy is reminiscent of that used to design a currently licensed and successful 23-valent pneumococcus vaccine. Three recombinant vector systems are used for the delivery of envelope cocktails (DNA, vaccinia virus, and purified protein) and each of these has been tested individually in phase I safety trials. A fourth clinical trial, in which diverse envelopes and vectors are combined in a prime-boost vaccination regimen, has been FDA-approved and is expected to commence in 2007. This trial will continue to test the hypothesis that a multivector, multi-envelope vaccine can elicit diverse 8- and T-cell populations that can prevent HIV-1 infections in humans.

Maternal self-efficacy regarding children's eating and sedentary behaviours in the early years : Associations with children's food intake and sedentary behaviours

Introduction. This cross-sectional study aimed to describe parents' views regarding self-efficacy to influence children's eating and sedentary behaviours at two time points in early childhood, and to examine associations between these views and children's eating and sedentary behaviours.

Methods. Mothers of 1-year (n=60) and 5-year-old children (n=80) were recruited through Maternal and Child Health Centres and kindergartens in Victoria, Australia. Mothers reported children's dietary intake, television viewing and perceptions of their self-efficacy regarding children's eating and sedentary behaviours.

Results. Overall, 5-year-old children consumed significantly more energy-dense food and drink and spent significantly more time viewing TV/DVD and video. Mothers of 1-year-olds were significantly more likely to report they felt confident to limit child's consumption of non-core foods/drinks, and to limit screen access (p<0.001). Measures of maternal self-efficacy were directly associated with 5-year-old children's water (p<0.05), and fruit and vegetable consumption (p<0.005), and with 1-year-old children's vegetable consumption (p<0.05), and were inversely associated with cordial and cake consumption (p<0.05). Maternal self-efficacy to limit viewing time was inversely associated with screen-time exposure in both age groups (p<0.01).

Conclusion. This study suggests that mother's self-efficacy regarding limiting non-core foods/drinks and limiting screen-time exposures may decline during the first few years of a child's life. Higher maternal self-efficacy was associated with children having more obesity protective eating and sedentary behaviours at both ages. Interventions to support the development of healthy lifestyle behaviours may be most effective if they target mothers' self-efficacy in these domains early in their child's life.

Knowledge of human papillomavirus (HPV) and the HPV vaccine in a national sample of Australian men and women

Background: Human papillomavirus (HPV) knowledge has rarely been investigated in the context of a national vaccination program. The present study investigated HPV knowledge after the introduction of a national HPV vaccination program in Australia using a national sample of men and women. Methods: Questions assessing HPV knowledge were part of a broader national study of health and relationships administered via a computer-assisted telephone interview. These findings are from wave four of the study, conducted between 2007 and 2008. Knowledge questions about HPV included its association with cervical cancer, genital warts and abnormal Pap tests. Results: A total of 2634 women and 2556 men between the ages of 18 and 70 were interviewed. Overall, 62.8% (95% confidence interval (CI): 60.8–64.7%) of women and 38.3% (95% CI: 36.3–40.4%) of men had heard of HPV. Of these, 66.0% (95% CI: 64.1–67.9%) correctly answered that HPV is associated with cervical cancer, 50.2% (95% CI: 48.2–52.1%) answered that HPV is associated with abnormal Pap tests and 44.5% (95% CI:42.5–46.5%) answered that HPV causes warts. Predictors of good knowledge included being female, aged between 26 and 45, holding higher education levels and older age at first sex. Ever having a Pap test was also associated with awareness about HPV. Conclusion: One of the highest levels of knowledge about HPV in Australia to date is reported in the present study. Knowledge about the association between HPV and cervical cancer was particularly high, especially when compared with knowledge of the association with genital warts. This appears to be a consequence of the marketing of the HPV vaccine as a vaccination against cervical cancer.

The efficacy of partnership evaluation and its impact on alliance transformation : a case study 12 months post evaluation

Partnerships involving higher education, governments, and industry have been recognised as important vehicles for engaging community, leveraging knowledge, and sharing potential resources. The critical need for these partnerships in rural and regional locations has been of particular note. Partnership evaluation can serve a critical function of informing continuous improvement and may therefore assist the evaluated agencies to work towards responsive transformational change. The ability for a partnership to adapt and change may aid in their sustainability. Despite the potentially important role of partnership evaluation, the development of tools that measure partnership are at an early stage. Partnership evaluation is rarely reflected upon in the published literature. Moreover, benefits and reflections of the efficacy of evaluations 12 months post analysis is rare in the published literature. Therefore, a brief review of partnership approaches and measurement tools are presented. The purpose of this paper is to reflect upon the efficacy of an evaluation conducted 12 months previously of a partnership between Deakin University, the Department of Health and Department of Human Services (Barwon South West Region), known as the Deakin/DH/DHS Strategic Alliance. This case study reviews several tools/metrics utilised. The efficacy of the evaluation tools is discussed. Those metrics, underlying the tools which contributed to positive change in partnerships are discussed.

Efficacy of atypical antipsychotics in bipolar disorder

Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies. Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder. The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.

Olanzapine / fluoxetine combination for treatment resistant depression : efficacy and clinical utility

Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient’s personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery–Åsberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

Multidimensional evaluation framework for virtual environment efficacy assessment

This research is related to the user-centred design and use of Virtual Environment (VE) training systems. A multidimensional user-centred systematic training evaluation framework that combines ideas from human-computer interaction, training, education and psychology was proposed, which contributes to better design and evaluation of VE user interfaces.

Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies.

Functional analysis of Plasmodium falciparum merozoite antigens : implications for erythrocyte invasion and vaccine development

Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.

Efficacy of a referral and physical activity program for survivors of prostate cancer [ENGAGE] : rationale and design for a cluster randomised controlled trial

Background: Despite evidence that physical activity improves the health and well-being of prostate cancer survivors, many men do not engage in sufficient levels of activity. The primary aim of this study (ENGAGE) is to determine the efficacy of a referral and physical activity program among survivors of prostate cancer, in terms of increasing participation in physical activity. Secondary aims are to determine the effects of the physical activity program on psychological well-being, quality of life and objective physical functioning. The influence of individual and environmental mediators on participation in physical activity will also be determined.
Methods/Design: This study is a cluster randomised controlled trial. Clinicians of prostate cancer survivors will be randomised into either the intervention or control condition. Clinicians in the intervention condition will refer eligible patients (n = 110) to participate in an exercise program, comprising 12 weeks of supervised exercise sessions and unsupervised physical activity. Clinicians allocated to the control condition will provide usual care to eligible patients (n = 110), which does not involve the recommendation of the physical activity program. Participants will be assessed at baseline, 12 weeks, 6 months, and 12 months on physical activity, quality of life, anxiety, depression, self-efficacy, outcome expectations, goals, and socio-structural factors.
Discussion: The findings of this study have implications for clinicians and patients with different cancer types or other chronic health conditions. It will contribute to our understanding on the potential impact of clinicians promoting physical activity to patients and the long term health benefits of participating in physical activity programs.

Family-centred practice : empowerment, self-efficacy, and challenges for practitioners in early childhood education and care

Family-centred practice has been included in the Victoria, Australia Early Years Learning and Development Framework as a key practice principle for professionals working across all early years programs in that state. While this model of partnership for engaging and collaborating with families has long been used in the early intervention sector, the efficacy of adopting this model more widely across the wider early childhood education and care sector has not been explored. This article presents a discussion on family-centred practice as a model for engaging with families in the care and education of their children. Through an analysis of the underlying philosophy and an examination of the core principles and characteristics, the article explores family-centred practice as it sits within a broader theory of partnership. This analysis identifies that while there are essential principles and characteristics that position the model within a partnership framework, it is the notion of empowerment, an underpinning philosophy guiding the model, that adds another dimension to the way practitioners in early childhood education and care settings collaborate with families. In examining the broader early childhood context, the capacity of many early childhood practitioners to effectively implement empowering behaviours is challenged.

Parental influences on adolescent fruit consumption : the role of adolescent self-efficacy

The aims of this study were to examine whether adolescent self-efficacy mediates the associations between parental control, perceptions of the importance of healthy nutrition for child health and barriers to buying fruits and vegetables and adolescent fruit consumption using a theoretically derived explanatory model. Data were drawn from a community-based sample of 1606 adolescents in Years 7 and 9 of secondary school and their parents, from Victoria, Australia. Adolescents completed a web-based survey assessing their fruit consumption and self-efficacy for increasing fruit consumption. Parents completed a survey delivered via mail assessing parental control, perceptions and barriers to buying fruit and vegetables. Adolescent self-efficacy for increasing fruit consumption mediated the positive associations between parental control and perceptions of the importance of healthy nutrition for child health and adolescent fruit consumption. Furthermore, adolescent self-efficacy mediated the negative association between parental barriers to buying fruits and vegetables and adolescent fruit consumption. The importance of explicating the mechanisms through which parental factors influence adolescent fruit consumption not only relates to the advancement of scientific knowledge but also offers potential avenues for intervention. Future research should assess the effectiveness of methods to increase adolescent fruit consumption by focussing on both improving adolescents’ dietary self-efficacy and on targeting parental control, perceptions and barriers.

An in vitro comparative assessment with a series of new triphenyltin(IV) 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with anticancer activities: Structural modifications, analysis of efficacy and cytotoxicity involving human tumor cell lines

Four new triphenyltin(IV) complexes of composition Ph₃SnLH (where LH = 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoate) (1–4) were synthesized and characterized by spectroscopic (¹H, ¹³C and ¹¹⁹Sn NMR, IR, ¹¹⁹Sn Mössbauer) techniques in combination with elemental analysis. The ¹¹⁹Sn NMR spectroscopic data indicate a tetrahedral coordination geometry in non-coordinating solvents. The crystal structures of three complexes, Ph₃SnL¹H (1), Ph₃SnL³H (3), Ph₃SnL⁴H (4), were determined. All display an essentially tetrahedral geometry with angles ranging from 93.50(8) to 124.5(2)°; ¹¹⁹Sn Mössbauer spectral data support this assignment. The cytotoxicity studies were performed with complexes 1–4, along with a previously reported complex (5) in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The screening results were compared with the results from other related triphenyltin(IV) complexes (6–7) and tributyltin(IV) complexes (8–11) having 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates framework. In general, the complexes exhibit stronger cytotoxic activity. The results obtained for 1–3 are also comparable to those of its o-analogs i.e. 4–7, except 5, but the advantage is the former set of complexes demonstrated two folds more cytotoxic activity for the cell line MCF-7 with ID₅₀ values in the range 41–53 ng/ml. Undoubtedly, the cytotoxic results of complexes 1–3 are far superior to CDDP, 5-FU and ETO, and related tributyltin(IV) complexes 8–11. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of triphenyltin(IV) complexes 1–7 and tributyltin(IV) complexes 8–11 is also discussed against a panel of human tumor cell lines.