An agent-based approach to immune modelling

This study focuses on trying to understand why the range of experience with respect to HIV infection is so diverse, especially as regards to the latency period. The challenge is to determine what assumptions can be made about the nature of the experience of antigenic invasion and diversity that can be modelled, tested and argued plausibly. To investigate this, an agent-based approach is used to extract high-level behaviour which cannot be described analytically from the set of interaction rules at the cellular level. A prototype model encompasses local variation in baseline properties contributing to the individual disease experience and is included in a network which mimics the chain of lymphatic nodes. Dealing with massively multi-agent systems requires major computational efforts. However, parallelisation methods are a natural consequence and advantage of the multi-agent approach. These are implemented using the MPI library.

Considerations for a social and geographical framework for agent-based epidemics

Understanding the dynamics of disease spread is of crucial importance, in contexts such as estimating load on medical services to risk assessment and intervention policies against large-scale epidemic outbreaks. However, most of the information is available after the spread itself, and preemptive assessment is far from trivial. Here, we investigate the use of agent-based simulations to model such outbreaks in a stylised urban environment. For most diseases, infection of a new individual may occur from casual contact in crowds as well as from repeated interactions with social partners such as work colleagues or family members. Our model therefore accounts for these two phenomena.Presented in this paper is the initial framework for such a model, detailing implementation of geographical features and generation of social structures. Preliminary results are a promising step towards large-scale simulations and evaluation of potential intervention policies.

Road operation phase sustainability indicator as a response to the climate change phenomena

Road infrastructure is a major contributor of greenhouse gas (GHG) around the world. Once constructed, a road becomes a part of a road network and is subjected to recurrent maintenance/rehabilitation activities. Studies to date are mostly aimed at the development of sustainability indicators that deal with the material and construction phases of a road when it is constructed. The operation phase is infrequently studied and there is a need for sustainability indicators to be developed relating to this phase to better understand the GHG emissions as a proper response to the climate change phenomena. During the operation phase, maintenance/rehabilitation activities are undertaken based on certain agreed intervention criteria that do not include environmental implications relating to the climate change aspect properly. Availability of appropriate indicators may, therefore, assist in sustainable road asset maintenance management. This paper presents the findings of a literature based study and has proposed a way forward to develop a key “road operation phase” environmental indicator, which can contribute to road operation phase carbon footprint management based on a comprehensive road life cycle system boundary model. The proposed indicator can address multiple aspects of high impact road operation life environmental components such as: pavement rolling resistance, albedo, material, traffic congestion and lighting, based on availability of relevant scientific knowledge. Development of the indicator to appropriate level would offset the impacts of these components significantly and contribute to sustainable road operation management.

Prospective ten-month exercise intervention in premenarcheal girls: Positive effects on bone and lean mass

Enhancement of bone mineral acquisition during growth may be a useful preventive strategy against osteoporosis. The aim of this study was to explore the lean mass, strength, and bone mineral response to a 10-month, high-impact, strength-building exercise program in 71 premenarcheal girls, aged 9–10 years. Lean body mass, total body (TB), lumbar spine (LS), proximal femur (PF), and femoral neck (FN) bone mineral were measured using the Hologic QDR 2000+ bone densitometer. Strength was assessed using a grip dynamometer and the Cybex isokinetic dynamometer (Cybex II). At baseline, no significant difference in body composition, pubertal development, calcium intake, physical activity, strength, or bone mineral existed between groups. At completion, there were again no differences in height, total body mass, pubertal development, calcium intake, or external physical activity. In contrast, the exercise group gained significantly more lean mass, less body fat content, greater shoulder, knee and grip strength, and greater TB, LS, PF, and FN BMD (exercise: TB 3.5%, LS 4.8%, PF 4.5%, and FN 12.0%) compared with the controls (controls: TB 1.2%, LS 1.2%, PF 1.3%, and FN 1.7%). TB bone mineral content (BMC), LS BMC, PF BMC, FN BMC, LS bone mineral apparent density (BMAD), and FN bone area also increased at a significantly greater rate in the exercise group compared with the controls. In multiple regression analysis, change in lean mass was the primary determinant of TB, FN, PF, and LS BMD accrual. Although a large proportion of bone mineral accrual in the premenarcheal skeleton was related to growth, an osteogenic effect was associated with exercise. These results suggest that high-impact, strength building exercise is beneficial for premenarcheal strength, lean mass gains, and bone mineral acquisition.

Nursing and medical perceptions of a hospital rapid response system: New process but same old game?

Perhaps no other patient safety intervention depends so acutely on effective interprofessional teamwork for patient survival than the hospital rapid response system (RRS). Yet little is known about nurse-physician relationships when rescuing at-risk patients. This study compared nursing and medical staff perceptions of a mature RRS at a large tertiary hospital. Findings indicate the RRS may be failing to address a hierarchical culture and systems-level barriers to early recognition and response to patient deterioration.

Action or inaction: bystander intervention in workplace sexual harassment

A promising approach to the persistent problem of workplace sexual harassment (SH) is encouraging interventions by bystanders. Adopting a typology developed by Bowes-Sperry and O'Leary-Kelly that considers the level of immediacy and involvement of bystander interventions, this study explored 74 detailed descriptions of SH events that occurred in Australian workplaces. The findings reveal that despite the hidden nature of SH, there is significant involvement of actors who are not direct targets but their actions are frequently delayed, temporary or ineffective. The study makes two contributions to the study and practice of HRM. First, it provides important evidence of the different ways that bystanders respond to SH in real workplaces and the relative likelihood of these actions. Second, the study points to relevant contextual features evident in the scenarios described which determine if and how bystanders intervene. We discuss the utility of the bystander framework for future research and practice, including the development of bystander interventions as a potentially innovative response to the persistent and damaging problem of workplace SH.

The window of opportunity: A relevant concept for axial spondyloarthritis

The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial spondyloarthritis and established ankylosing spondylitis. In axial spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.

Evaluation of a skin self examination attitude scale using an item response theory model approach

Introduction The Skin Self-Examination Attitude Scale (SSEAS) is a brief measure that allows for the assessment of attitudes in relation to skin self-examination. This study evaluated the psychometric properties of the SSEAS using Item Response Theory (IRT) methods in a large sample of men ≥ 50 years in Queensland, Australia. Methods A sample of 831 men (420 intervention and 411 control) completed a telephone assessment at the 13-month follow-up of a randomized-controlled trial of a video-based intervention to improve skin self-examination (SSE) behaviour. Descriptive statistics (mean, standard deviation, item–total correlations, and Cronbach’s alpha) were compiled and difficulty parameters were computed with Winsteps using the polytomous Rasch Rating Scale Model (RRSM). An item person (Wright) map of the SSEAS was examined for content coverage and item targeting. Results The SSEAS have good psychometric properties including good internal consistency (Cronbach’s alpha = 0.80), fit with the model and no evidence for differential item functioning (DIF) due to experimental trial grouping was detected. Conclusions The present study confirms the SSEA scale as a brief, useful and reliable tool for assessing attitudes towards skin self-examination in a population of men 50 years or older in Queensland, Australia. The 8-item scale shows unidimensionality, allowing levels of SSE attitude, and the item difficulties, to be ranked on a single continuous scale. In terms of clinical practice, it is very important to assess skin cancer self-examination attitude to identify people who may need a more extensive intervention to allow early detection of skin cancer.

Randomised clinical trial of a family-based lifestyle intervention for childhood obesity involving parents as the exclusive agents of change

Parent-centred interventions for childhood obesity aim to improve parents' skills and confidence in managing children's dietary and activity patterns, and in promoting a healthy lifestyle in their family. However, few studies assess changes in parenting over the course of treatment. This study describes the evaluation of a lifestyle-specific parenting program (Group Lifestyle Triple P) on multiple child and parent outcomes. One-hundred-and-one families with overweight and obese 4- to 11-year-old children participated in an intervention or waitlist control condition. The 12-week intervention was associated with significant reductions in child BMI z score and weight-related problem behaviour. At the end of the intervention, parents reported increased confidence in managing children's weight-related behaviour, and less frequent use of inconsistent or coercive parenting practices. All short-term intervention effects were maintained at one-year follow-up assessment, with additional improvements in child body size. The results support the efficacy of Group Lifestyle Triple P and suggest that parenting influences treatment outcomes. Further research is needed to evaluate the long-term effectiveness of the intervention and to elucidate the mechanisms of change. © 2010 Elsevier Ltd.

Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

A potent nonporphyrin class of photodynamic therapeutic agent: Cellular localisation, cytotoxic potential and influence of hypoxia

We have developed a totally new class of nonporphyrin photodynamic therapeutic agents with a specific focus on two lead candidates azadipyrromethene (ADPM)01 and ADPM06. Confocal laser scanning microscopy imaging showed that these compounds are exclusively localised to the cytosolic compartment, with specific accumulation in the endoplasmic reticulum and to a lesser extent in the mitochondria. Light-induced toxicity assays, carried out over a broad range of human tumour cell lines, displayed EC50 values in the micro-molar range for ADPM01 and nano-molar range for ADPM06, with no discernable activity bias for a specific cell type. Strikingly, the more active agent, ADPM06, even retained significant activity under hypoxic conditions. Both photosensitisers showed low to nondeterminable dark toxicity. Flow cytometric analysis revealed that ADPM01 and ADPM06 were highly effective at inducing apoptosis as a mode of cell death. The photophysical and biological characteristics of these PDT agents suggest that they have potential for the development of new anticancer therapeutics. © 2005 Cancer Research UK.

Potential antioxidant response to coffee - A matter of genotype?

In a human intervention trial, a coffee, combining nature green coffee bean constituents and dark roast products was studied towards its potential to activate the Nrf2/ARE-pathway in PBLs. The study coffee was identified as a strong inducer of Nrf2 and downstream GST1A1 and UGT1A1 gene transcription. However, the response of the participants was found to depend on the respective genotype. The -651 SNP in the Nrf2 gene as well as the heterozygote 6/7 sequence in the UGT1A1 gene significantly down-regulated the susceptibility to respond to coffee, proposing the existing genotype to be critical for the response to the coffee.