Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone

The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.

A Bayesian regression approach to assess uncertainty in pollutant wash-off modelling

Due to knowledge gaps in relation to urban stormwater quality processes, an in-depth understanding of model uncertainty can enhance decision making. Uncertainty in stormwater quality models can originate from a range of sources such as the complexity of urban rainfall-runoff-stormwater pollutant processes and the paucity of observed data. Unfortunately, studies relating to epistemic uncertainty, which arises from the simplification of reality are limited and often deemed mostly unquantifiable. This paper presents a statistical modelling framework for ascertaining epistemic uncertainty associated with pollutant wash-off under a regression modelling paradigm using Ordinary Least Squares Regression (OLSR) and Weighted Least Squares Regression (WLSR) methods with a Bayesian/Gibbs sampling statistical approach. The study results confirmed that WLSR assuming probability distributed data provides more realistic uncertainty estimates of the observed and predicted wash-off values compared to OLSR modelling. It was also noted that the Bayesian/Gibbs sampling approach is superior compared to the most commonly adopted classical statistical and deterministic approaches commonly used in water quality modelling. The study outcomes confirmed that the predication error associated with wash-off replication is relatively higher due to limited data availability. The uncertainty analysis also highlighted the variability of the wash-off modelling coefficient k as a function of complex physical processes, which is primarily influenced by surface characteristics and rainfall intensity.

Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer

Objective To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer. Methods 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3–5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorised as: Women with LLL (n = 68), women with LLS (n = 177) and women without LLL or LLS (n = 394). Multivariable-adjusted generalized linear models were used to compare women’s physical and mental QoL by LLL status. Results On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M= 41.8, SE= 1.4) than women without LLL or LLS (M= 45.1, SE= 0.8, p = .07), however, their mental QoL was within the normative range (M= 49.6; SE= 1.1 p = 1.0). Women with LLS had significantly lower physical (M= 41.0, SE= 1.0, p = .003) and mental QoL (M= 46.8; SE= 0.8, p < .0001) than women without LLL or LLS (Mental QoL: M= 50.6, SE= 0.8). Conclusion Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women’s QoL.

Gelatine methacrylamide-based hydrogels : an alternative three-dimensional cancer cell culture system

Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly influenced hydrogel stiffness (0.5±0.2kPa to 9.0±1.8kPa) but had little effect on solute diffusion. The diffusion coefficient of 70kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33-37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.

A Cyber-Physical System Simulator for risk-free transport studies

The article introduces a novel platform for conducting controlled and risk-free driving and traveling behavior studies, called Cyber-Physical System Simulator (CPSS). The key features of CPSS are: (1) simulation of multiuser immersive driving in a threedimensional (3D) virtual environment; (2) integration of traffic and communication simulators with human driving based on dedicated middleware; and (3) accessibility of multiuser driving simulator on popular software and hardware platforms. This combination of features allows us to easily collect large-scale data on interesting phenomena regarding the interaction between multiple user drivers, which is not possible with current single-user driving simulators. The core original contribution of this article is threefold: (1) we introduce a multiuser driving simulator based on DiVE, our original massively multiuser networked 3D virtual environment; (2) we introduce OpenV2X, a middleware for simulating vehicle-to-vehicle and vehicle to infrastructure communication; and (3) we present two experiments based on our CPSS platform. The first experiment investigates the “rubbernecking” phenomenon, where a platoon of four user drivers experiences an accident in the oncoming direction of traffic. Second, we report on a pilot study about the effectiveness of a Cooperative Intelligent Transport Systems advisory system.

Promoting active lifestyles in young children: investigating mothers’ decisions about their child’s physical activity and screen time behaviours

Objectives Given increasing trends of obesity being noted from early in life and that active lifestyles track across time, it is important that children at a very young age be active to combat a foundation of unhealthy behaviours forming. This study investigated, within a theory of planned behaviour (TPB) framework, factors which influence mothers’ decisions about their child’s 1) adequate physical activity (PA) and 2) limited screen time behaviours. Methods Mothers (N = 162) completed a main questionnaire, via on-line or paper-based administration, which comprised standard TPB items in addition to measures of planning and background demographic variables. One week later, consenting mothers completed a follow-up telephone questionnaire which assessed the decisions they had made regarding their child’s PA and screen time behaviours during the previous week. Results Hierarchical multiple regression analyses revealed support for the predictive model, explaining an overall 73% and 78% of the variance in mothers’ intention and 38% and 53% of the variance in mothers’ decisions to ensure their child engages in adequate PA and limited screen time, respectively. Attitude and subjective norms predicted intention in both target behaviours, as did intentions with behaviour. Contrary to predictions, perceived behavioural control (PBC) in PA behaviour and planning in screen time behaviour were not significant predictors of intention, neither was PBC a predictor of either behaviour. Conclusions The findings illustrate the various roles that psycho-social factors play in mothers’ decisions to ensure their child engages in active lifestyle behaviours which can help to inform future intervention programs aimed at combating very young children’s inactivity.

Do community-wide interventions increase physical activity? S1TEP

Background Not getting enough physical activity leads to poorer health. Regular physical activity can reduce the risk of chronic disease and improve one’s health and well-being. The lack of physical activity is a common and growing problem in many countries. We sought to evaluate the effects of community wide, multi-strategic interventions upon the physical activity patterns of populations. Method We undertook a Cochrane Systematic Review which included an extensive search of databases, including studies which met pre-determined criteria, and conducted independent risk of bias assessment and data extraction. Results After the selection process, 25 studies were included in the review. The strategies varied by the number and type of components and their intensity. No studies were identified as low risk of bias. Sixteen studies were identified as having a high risk of bias and thus untrustworthy. Nine studies were of considered to have an unclear risk of bias and some studies held back data they collected. The effects reported were inconsistent across the studies and the measures. Some of the better designed studies showed no improvement in measures of physical activity. Interventions which have an environmental change component seemed to be a promising direction. Those interventions which were primarily a mass media campaign were less likely to be successful. Conclusions Although numerous studies have been undertaken, there is considerable inconsistency in the findings of the available studies and this is confounded by serious methodological issues within the included studies. Simply combining interventions does not necessarily result in increased physical activity as many such studies, including some long term programs, failed to demonstrate efficacy. There is a clear need for well-designed studies and these studies should focus on the quality of measurement of physical activity. The review is currently being updated with newer studies.

Evidence of effectiveness : high level synthesis of research to prevent obesity and increase physical activity in children

Background Prevention of childhood obesity is a public health priority for Malaysia and many other countries. Physical activity for children is also decreasing at an alarming rate. Both conditions are associated with non-communicable diseases and with significant morbidity and mortality in later life. Systematic reviews of public health interventions provide a useful summary to inform public health practice by combining the results of a range of research studies on a specific intervention into a single report. Systematic reviews are deemed most valuable for health program development and evidence based practice. Unfortunately, many policy makers and practitioners are simply unaware of the evidence: which strategies which are most likely to provide benefit; and which strategies are known to be harmful or useless. This presentation provides a “birds eye” overview based upon recent (since 2007 to present) high quality systematic reviews of public health interventions. Method HealthEvidece.org and the Cochrane Library were searched for systematic reviews which evaluated interventions targeting obesity prevention and increasing physical activity for children. The findings of the included reviews were themed and summarized. Results Seven reviews were identified addressing obesity in the early years, and fifteen reviews addressing obesity more broadly in childhood. Additional reviews were identified aimed at increasing physical activity. The synthesis shows several strategies to be effective, however many popular strategies clearly are not. Several of the reviews were inconclusive due to an absence of robust primary studies. Amongst the findings, interventions undertaken in the school setting appear very promising. Conclusions There is significant evidence from systematic reviews to guide public health practice and policy, and to inform future research.

Interactions between organizational culture, trustworthiness, and mechanisms for inter-project knowledge sharing

This research used a multiple-case study approach to empirically investigate the complex relationship between factors influencing inter-project knowledge sharing—trustworthiness, organizational culture, and knowledge-sharing mechanisms. Adopting a competing values framework, we found evidence of patterns existing between the type of culture, on the project management unit level, and project managers’ perceptions of valuing trustworthy behaviors and the way they share knowledge, on the individual level. We also found evidence for mutually reinforcing the effect of trust and clan culture, which shape tacit knowledge-sharing behaviors.

Isolation and characterization of charge-tagged phenylperoxyl radicals in the gas phase : direct evidence for products and pathways in low temperature benzene oxidation

The phenylperoxyl radical has long been accepted as a critical intermediate in the oxidation of benzene and an archetype for arylperoxyl radicals in combustion and atmospheric chemistry. Despite being central to many contemporary mechanisms underpinning these chemistries, reports of the direct detection or isolation of phenylperoxyl radicals are rare and there is little experimental evidence connecting this intermediate with expected product channels. We have prepared and isolated two charge-tagged phenyl radical models in the gas phase [i.e., 4-(N,N,N-trimethylammonium) phenyl radical cation and 4-carboxylatophenyl radical anion] and observed their reactions with dioxygen by ion-trap mass spectrometry. Measured reaction rates show good agreement with prior reports for the neutral system (k(2)[(Me3N+)C6H4 center dot + O-2] = 2.8 x 10(-11) cm(3) molecule(-1) s(-1), Phi = 4.9%; k(2)[(-O2C)C6H4 center dot + O-2] = 5.4 x 10(-1)1 cm(3) molecule(-1) s(-1), Phi = 9.2%) and the resulting mass spectra provide unequivocal evidence for the formation of phenylperoxyl radicals. Collisional activation of isolated phenylperoxyl radicals reveals unimolecular decomposition by three pathways: (i) loss of dioxygen to reform the initial phenyl radical; (ii) loss of atomic oxygen yielding a phenoxyl radical; and (iii) ejection of the formyl radical to give cyclopentadienone. Stable isotope labeling confirms these assignments. Quantum chemical calculations for both charge-tagged and neutral phenylperoxyl radicals confirm that loss of formyl radical is accessible both thermodynamically and entropically and competitive with direct loss of both hydrogen atom and carbon dioxide.

Direct detection of additives and degradation products from polymers by liquid extraction surface analysis employing chip-based nanospray mass spectrometry

RATIONALE: Polymer-based surface coatings in outdoor applications experience accelerated degradation due to exposure to solar radiation, oxygen and atmospheric pollutants. These deleterious agents cause undesirable changes to the aesthetic and mechanical properties of the polymer, reducing its lifetime. The use of antioxidants such as hindered amine light stabilisers (HALS) retards these degradative processes; however, mechanisms for HALS action and polymer degradation are poorly understood. METHODS: Detection of the HALS TINUVINW123 (bis(1-octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate) and the polymer degradation products directly from a polyester-based coil coating was achieved by liquid extraction surface analysis (LESA) coupled to a triple quadrupole QTRAPW 5500 mass spectrometer. The detection of TINUVINW123 and melamine was confirmed by the characteristic fragmentation pattern observed in LESA-MS/MS spectra that was identical to that reported for authentic samples. RESULTS: Analysis of an unstabilised coil coating by LESA-MS after exposure to 4 years of outdoor field testing revealed the presence of melamine (1,3,5-triazine-2,4,6-triamine) as a polymer degradation product at elevated levels. Changes to the physical appearance of the coil coating, including powder-like deposits on the coating's surface, were observed to coincide with melamine deposits and are indicative of the phenomenon known as polymer ' blooming'. CONCLUSIONS: For the first time, in situ detection of analytes from a thermoset polymer coating was accomplished without any sample preparation, providing advantages over traditional extraction-analysis approaches and some contemporary ambient MS methods. Detection of HALS and polymer degradation products such as melamine provides insight into the mechanisms by which degradation occurs and suggests LESA-MS is a powerful new tool for polymer analysis. Copyright (C) 2012 John Wiley & Sons, Ltd.

Are in vitro estimates of cell diffusivity and cell proliferation rate sensitive to assay geometry?

Cells respond to various biochemical and physical cues during wound–healing and tumour progression. In vitro assays used to study these processes are typically conducted in one particular geometry and it is unclear how the assay geometry affects the capacity of cell populations to spread, or whether the relevant mechanisms, such as cell motility and cell proliferation, are somehow sensitive to the geometry of the assay. In this work we use a circular barrier assay to characterise the spreading of cell populations in two different geometries. Assay 1 describes a tumour–like geometry where a cell population spreads outwards into an open space. Assay 2 describes a wound–like geometry where a cell population spreads inwards to close a void. We use a combination of discrete and continuum mathematical models and automated image processing methods to obtain independent estimates of the effective cell diffusivity, D, and the effective cell proliferation rate, λ. Using our parameterised mathematical model we confirm that our estimates of D and λ accurately predict the time–evolution of the location of the leading edge and the cell density profiles for both assay 1 and assay 2. Our work suggests that the effective cell diffusivity is up to 50% lower for assay 2 compared to assay 1, whereas the effective cell proliferation rate is up to 30% lower for assay 2 compared to assay 1.

Pulsed wall jet simulation of a stationary thunderstorm downburst, Part A: Physical structure and flow field characterization

A pulsed wall jet has been used to simulate the gust front of a thunderstorm downburst. Flow visualization, wind speed and surface pressure measurements were obtained. The characteristics of the hypothesized ring vortex of a full-scale downburst were reproduced at a scale estimated to be 1:3000.

Smart material interfaces : a new form of physical interaction

Smart Material Interface (SMI) is the latest generation of user interface that makes use of engineered materials and leverages their special properties. SMIs are capable of changing their physical properties such as shape, size and color, and can be controlled under certain (external) conditions. We provide an example of such an SMI in the form of a prototype of a vacuum cleaner. The prototype uses schematic electrochromic polymer at the suction nozzle of the vacuum cleaner, which changes its color depending on the dust level on a floor. We emphasize on the new affordances and communication language supported by SMIs, which challenges the current metaphors of user interfaces in the field of HCI.

Numerical estimation of 3D mechanical forces exerted by cells on non-linear materials

The exchange of physical forces in both cell-cell and cell-matrix interactions play a significant role in a variety of physiological and pathological processes, such as cell migration, cancer metastasis, inflammation and wound healing. Therefore, great interest exists in accurately quantifying the forces that cells exert on their substrate during migration. Traction Force Microscopy (TFM) is the most widely used method for measuring cell traction forces. Several mathematical techniques have been developed to estimate forces from TFM experiments. However, certain simplifications are commonly assumed, such as linear elasticity of the materials and/or free geometries, which in some cases may lead to inaccurate results. Here, cellular forces are numerically estimated by solving a minimization problem that combines multiple non-linear FEM solutions. Our simulations, free from constraints on the geometrical and the mechanical conditions, show that forces are predicted with higher accuracy than when using the standard approaches.