Modelling and prediction of bacterial attachment to polymers

Infection by pathogenic bacteria on implanted and indwelling medical devices during surgery causes large morbidity and mortality worldwide. Attempts to ameliorate this important medical issue have included development of antimicrobial surfaces on materials, ‘no touch’ surgical procedures, and development of materials with inherent low pathogen attachment. The search for new materials is increasingly being carried out by high throughput methods. Efficient methods for extracting knowledge from these large data sets are essential. We used data from a large polymer microarray exposed to three clinical pathogens to derive robust and predictive machine-learning models of pathogen attachment. The models could predict pathogen attachment for the polymer library quantitatively. The models also successfully predicted pathogen attachment for a second-generation library, and identified polymer surface chemistries that enhance or diminish pathogen attachment

A Visual Analytics Approach to Debugging Cooperative, Autonomous Multi-Robot Systems' Worldviews

Autonomous multi-robot systems, where a team of robots shares information to perform tasks that are beyond an individual robot's abilities, hold great promise for a number of applications, such as planetary exploration missions. Each robot in a multi-robot system that uses the shared-world coordination paradigm autonomously schedules which robot should perform a given task, and when, using its worldview--the robot's internal representation of its belief about both its own state, and other robots' states. A key problem for operators is that robots' worldviews can fall out of sync (often due to weak communication links), leading to desynchronization of the robots' scheduling decisions and inconsistent emergent behavior (e.g., tasks not performed, or performed by multiple robots). Operators face the time-consuming and difficult task of making sense of the robots' scheduling decisions, detecting de-synchronizations, and pinpointing the cause by comparing every robot's worldview. To address these challenges, we introduce MOSAIC Viewer, a visual analytics system that helps operators (i) make sense of the robots' schedules and (ii) detect and conduct a root cause analysis of the robots' desynchronized worldviews. Over a year-long partnership with roboticists at the NASA Jet Propulsion Laboratory, we conduct a formative study to identify the necessary system design requirements and a qualitative evaluation with 12 roboticists. We find that MOSAIC Viewer is faster- and easier-to-use than the users' current approaches, and it allows them to stitch low-level details to formulate a high-level understanding of the robots' schedules and detect and pinpoint the cause of the desynchronized worldviews.Comment: To appear in IEEE Conference on Visual Analytics Science and Technology (VAST) 202

High throughput methods applied in biomaterial development and discovery

The high throughput discovery of new materials can be achieved by rapidly screening many different materials synthesised by a combinatorial approach to identify the optimal material that fulfils a particular biomedical application. Here we review the literature in this area and conclude that for polymers, this process is best achieved in a microarray format, which enable thousands of cell-material interactions to be monitored on a single chip. Polymer microarrays can be formed by printing pre-synthesised polymers or by printing monomers onto the chip where on-slide polymerisation is initiated. The surface properties of the material can be analysed and correlated to the biological performance using high throughput surface analysis, including time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) measurements. This approach enables the surface properties responsible for the success of a material to be understood, which in turn provides the foundations of future material design. The high throughput discovery of materials using polymer microarrays has been explored for many cell-based applications including the isolation of specific cells from heterogeneous populations, the attachment and differentiation of stem cells and the controlled transfection of cells. Further development of polymerisation techniques and high throughput biological assays amenable to the polymer microarray format will broaden the combinatorial space and biological phenomenon that polymer microarrays can explore, and increase their efficacy. This will, in turn, result in the discovery of optimised polymeric materials for many biomaterial applications

Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup.

Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup

High-throughput characterization of fluid properties to predict droplet ejection for three-dimensional inkjet printing formulations

Inkjet printing has been used as an Additive Manufacturing (AM) method to fabricate three-dimensional (3D) structures. However, a lack of materials suitable for inkjet printing poses one of the key challenges that impedes industry from fully adopting this technology. Consequently, many industry sectors are required to spend significant time and resources on formulating new materials for an AM process, instead of focusing on product development. To achieve the spatially controlled deposition of a printed voxel in a predictable and repeatable fashion, a combination of the physical properties of the ‘ink’ material, print head design, and processing parameters is associated. This study demonstrates the expedited formulation of new inks through the adoption of a high-throughput screening (HTS) approach. Use of a liquid handler containing multi-pipette heads, to rapidly prepare inkjet formulations in a micro-array format, and subsequently measure the viscosity and surface tension for each in a high-throughput manner is reported. This automatic approach is estimated to be 15 times more rapid than conventional methods. The throughput is 96 formulations per 13.1 working hours, including sample preparation and subsequent printability determination. The HTS technique was validated by comparison with conventional viscosity and surface tension measurements, as well as the observation of droplet ejection during inkjet printing processes. Using this approach, a library of 96 acrylate/methacrylate materials was screened to identify the printability of each formulation at different processing temperatures. The methodology and the material database established using this HTS technique will allow academic and industrial users to rapidly select the most ideal formulation to deliver printability and a predicted processing window for a chosen application

Effect of surfactant on Pseudomonas aeruginosa colonization of polymer microparticles and flat films

Micro- and nanoparticles are of great interest because of their potential for trafficking into the body for applications such as low-fouling coatings on medical devices, drug delivery in pharmaceutics and cell carriers in regenerative medicine strategies. Particle production often relies on the use of surfactants to promote stable droplet formation. However, the presence of residual surfactant has been shown to complicate the surface chemistry and resultant properties. When forming particles from polymerizable monomer droplets, these polymeric surfactant chains can become physically entangled in the particle surface. Due to the key role of the outermost layers of the surface in biomaterial interactions, the surface chemistry and its influence on cells needs to be characterized. This is the first study to assess surfactant retention on microfluidic produced particles and its effect on bacterial attachment; surfactant contaminated microparticles are compared with flat films which are surfactant-free. Polymeric microparticles with an average diameter of 76 ± 1.7 μm were produced by using a T-junction microfluidic system to form monomer droplets which were subsequently photopolymerized. Acrylate based monomer solutions were found to require 2 wt% PVA to stabilize droplet formation. ToF-SIMS was employed to assess the surface chemistry revealing the presence of PVA in a discontinuous layer on the surface of microparticles which was reduced but not removed by solvent washing. The effect of PVA on bacterial (Pseudomonas aeruginosa) attachment was quantified and showed reduction as a function of the amount of PVA retained at the surface. The insights gained in this study help define the structure–function relationships of the particulate biomaterial architecture, supporting materials design with biofilm control

UV friendly T-parity in the SU(6)/Sp(6) little Higgs model

Electroweak precision tests put stringent constraints on the parameter space of little Higgs models. Tree-level exchange of TeV scale particles in a generic little Higgs model produce higher dimensional operators that make contributions to electroweak observables that are typically too large. To avoid this problem a discrete symmetry dubbed T-parity can be introduced to forbid the dangerous couplings. However, it was realized that in simple group models such as the littlest Higgs model, the implementation of T-parity in a UV completion could present some challenges. The situation is analogous to the one in QCD where the pion can easily be defined as being odd under a new $Z_2$ symmetry in the chiral Lagrangian, but this $Z_2$ is not a symmetry of the quark Lagrangian. In this paper we examine the possibility of implementing a T-parity in the low energy $SU(6)/Sp(6)$ model that might be easier to realize in the UV. In our model, the T-parity acts on the low energy non-linear sigma model field in way which is different to what was originally proposed for the Littlest Higgs, and lead to a different low energy theory. In particular, the Higgs sector of this model is a inert two Higgs doublets model with an approximate custodial symmetry. We examine the contributions of the various sectors of the model to electroweak precision data, and to the dark matter abundance.Comment: 21 pages,4 figures. Clarifications added, typos corrected and references added. Published in JHE

Pre-screening the intrinsic angiogenic capacity of biomaterials in an optimised ex ovo chorioallantoic membrane model

Biomaterial development for clinical applications is currently on the rise. This necessitates adequate in vitro testing, where the structure and composition of biomaterials must be specifically tailored to withstand in situ repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised ex ovo method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials’ angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed ex ovo chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application

Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy cow: a case report

A mature dairy cow was transitioned from a high forage (100% forage) to a high-grain (79% grain) diet over seven days. Continuous ruminal pH recordings were utilized to diagnose the severity of ruminal acidosis. Additionally, blood and rumen papillae biopsies were collected to describe the structural and functional adaptations of the rumen epithelium. On the final day of the grain challenge, the daily mean ruminal pH was 5.41 ± 0.09 with a minimum of 4.89 and a maximum of 6.31. Ruminal pH was under 5.0 for 130 minutes (2.17 hours) which is characterized as the acute form of ruminal acidosis in cattle. The grain challenge increased blood beta-hydroxybutyrate by 1.8 times and rumen papillae mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase by 1.6 times. Ultrastructural and histological adaptations of the rumen epithelium were imaged by scanning electron and light microscopy. Rumen papillae from the high grain diet displayed extensive sloughing of the stratum corneum and compromised cell adhesion as large gaps were apparent between cells throughout the strata. This case report represents a rare documentation of how the rumen epithelium alters its function and structure during the initial stage of acute acidosis