Sterilizing tissue-materials using pulsed power plasma

This paper investigates the potential of pulsed power to sterilize hard and soft tissues and its impact on their physico-mechanical properties. It hypothesizes that pulsed plasma can sterilize both vascular and avascular tissues and the transitive layers in between without deleterious effects on their functional characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the concept, treated at low temperature, at atmospheric pressure, in short durations and in buffered environment using a purposed-built pulsed power unit. Input voltage and time of exposure were assigned as controlling parameters in a full factorial design of experiment to determine physical and mechanical alteration pre- and post-treatment. The results demonstrated that, discharges of 11 kV sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 ± 0.9 to 0.9 ± 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in elastic-strain energy for the top quartile. Mechanical impairment was directly proportional to input voltage (P value < 0.05). Bacterial inactivation was proportional to treatment time for input voltages above 32 V (P < 0.001; R Sq = 0.98). Thermal analysis revealed that helix-coil transition decelerated with exposure time and collagen fibrils were destabilized as denaturation enthalpy reduced by 200 μV. We concluded by presenting a safe operating threshold for pulsed power plasma as a feasible protocol for effective sterilization of connective tissues with varying level of loss in mechanical robustness which we argue to be acceptable in certain medical and tissue engineering application.

Molecular dynamics investigation on shearing between osteopontin and hydroxyapatite in biological materials

Bone, a hard biological material, possesses a combination of high stiffness and toughness, even though the main basic building blocks of bone are simply mineral platelets and protein molecules. Bone has a very complex microstructure with at least seven hierachical levels. This unique material characteristic attracts great attention, but the deformation mechanisms in bone have not been well understood. Simulation at nano-length scale such as molecular dynamics (MD) is proven to be a powerful tool to investigate bone nanomechanics for developing new artificial biological materials. This study focuses on the ultra large and thin layer of extrafibrillar protein matrix (thickness = ~ 1 nm) located between mineralized collagen fibrils (MCF). Non-collagenous proteins such as osteopontin (OPN) can be found in this protein matrix, while MCF consists mainly of hydroxyapatite (HA) nanoplatelets (thickness = 1.5 – 4.5 nm). By using molecular dynamics method, an OPN peptide was pulled between two HA mineral platelets with water in presence. Periodic boundary condition (PBC) was applied. The results indicate that the mechanical response of OPN peptide greatly depends on the attractive electrostatics interaction between the acidic residues in OPN peptide and HA mineral surfaces. These bonds restrict the movement of OPN peptide, leading to a high energy dissipation under shear loading.

Toward biomimetic materials in bone regeneration : functional behavior of mesenchymal stem cells on a broad spectrum of extracellular matrix components

Bone defect treatments can be augmented by mesenchymal stem cell (MSC) based therapies. MSC interaction with the extracellular matrix (ECM) of the surrounding tissue regulates their functional behavior. Understanding of these specific regulatory mechanisms is essential for the therapeutic stimulation of MSC in vivo. However, these interactions are presently only partially understood. This study examined in parallel, for the first time, the effects on the functional behavior of MSCs of 13 ECM components from bone, cartilage and hematoma compared to a control protein, and hence draws conclusions for rational biomaterial design. ECM components specifically modulated MSC adhesion, migration, proliferation, and osteogenic differentiation, for example, fibronectin facilitated migration, adhesion, and proliferation, but not osteogenic differentiation, whereas fibrinogen enhanced adhesion and proliferation, but not migration. Subsequently, the integrin expression pattern of MSCs was determined and related to the cell behavior on specific ECM components. Finally, on this basis, peptide sequences are reported for the potential stimulation of MSC functions. Based on the results of this study, ECM component coatings could be designed to specifically guide cell functions.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application

Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted to new patients. Contact lenses became a popular mode of ophthalmic refractive error correction following the discovery of the first hydrogel material – hydroxyethyl methacrylate – by Czech chemist Otto Wichterle in 1960. To satisfy the requirements for ocular biocompatibility, contact lenses must be transparent and optically stable (for clear vision), have a low elastic modulus (for good comfort), have a hydrophilic surface (for good wettability), and be permeable to certain metabolites, especially oxygen, to allow for normal corneal metabolism and respiration during lens wear. A major breakthrough in respect of the last of these requirements was the development of silicone hydrogel soft lenses in 1999 and techniques for making the surface hydrophilic. The vast majority of contact lenses distributed worldwide are mass-produced using cast molding, although spin casting is also used. These advanced mass-production techniques have facilitated the frequent disposal of contact lenses, leading to improvements in ocular health and fewer complications. More than one-third of all soft contact lenses sold today are designed to be discarded daily (i.e., ‘daily disposable’ lenses).

Multidirectional effects of Sr, Mg and Si-containing bioceramic coatings with high bonding strength on inflammation, osteoclastogenesis and osteogenesis

Ideal coating materials for implants should be able to induce excellent osseointegration, which requires several important parameters, such as good bonding strength, limited inflammatory reaction, balanced osteoclastogenesis and osteogenesis, to gain well-functioning coated implants with long-term life span after implantation. Bioactive elements, like Sr, Mg and Si, have been found to play important roles in regulating the biological responses. It is of great interest to combine bioactive elements for developing bioactive coatings on Ti-6Al-4V orthopedic implants to elicit multidirectional effects on the osseointegration. In this study, Sr, Mg and Si-containing bioactive Sr2MgSi2O7 (SMS) ceramic coatings on Ti-6Al-4V were successfully prepared by plasma-spray coating method. The prepared SMS coatings have significantly higher bonding strength (~37MPa) than conventional pure hydroxyapatite (HA) coatings (mostly in the range of 15-25 MPa). It was also found that the prepared SMS coatings switch the macrophage phenotype into M2 extreme, inhibiting the inflammatory reaction via the inhibition of Wnt5A/Ca2+ and Toll-like receptor (TLR) pathways of macrophages. In addition, the osteoclastic activities were also inhibited by SMS coatings. The expression of osteoclastogenesis related genes (RANKL and MCSF) in bone marrow derived mesenchymal cells (BMSCs) with the involvement of macrophages was decreased, while OPG expression was enhanced on SMS coatings compared to HA coatings, indicating that SMS coatings also downregulated the osteoclastogenesis. However, the osteogenic differentiation of BMSCs with the involvement of macrophages was comparable between SMS and HA coatings. Therefore, the prepared SMS coatings showed multidirectional effects, such as improving bonding strength, reducing inflammatory reaction and downregulating osteoclastic activities, but maintaining a comparable osteogenesis, as compared with HA coatings. The combination of bioactive elements of Sr, Mg and Si into bioceramic coatings can be a promising method to develop bioactive implants with multifunctional properties for orthopaedic application.

Criminal Laws : Materials and Commentary on Criminal Law and Process in NSW [Fifth Edition]

"The success of Criminal Laws lies both in its distinctive features and in its appeal to a range of readerships. As one review put it, it is simultaneously a "textbook, casebook, handbook and reference work". As such it is ideal for criminal law and criminal justice courses as a teaching text, combining as it does primary sources with extensive critical commentary and a contextual perspective. It is likewise indispensable to practitioners for its detailed coverage of substantive law and its extensive references and inter-disciplinary approach make it a first point of call for researchers from all disciplines. This fifth edition strengthens these distinctive features. All chapters have been systematically updated to incorporate the plethora of legislative, case law, statistical and research material which has emerged since the previous edition. The critical, thematic, contextual and interdisciplinary perspectives have been continued."--Publisher's website. Table of Contents: 1. Some themes -- 2. Criminalisation -- 3. The criminal process -- 4. Components of criminal offences -- 5. Homicide: murder and involuntary manslaughter -- 6. Defences -- 7. Assault and sexual assault -- 8. Public order offences -- 9. Drugs offences -- 10. Dishonest acquisition -- 11. Extending criminal liability: complicity, conspiracy and association -- 12. Sentencing and penality.

Ecological consequences of fragmentation and deforestation in an urban landscape : a case study

Landscape change is an ongoing process even within established urban landscapes. Yet, analyses of fragmentation and deforestation have focused primarily on the conversion of non-urban to urban landscapes in rural landscapes and ignored urban landscapes. To determine the ecological effects of continued urbanization in urban landscapes, tree-covered patches were mapped in the Gwynns Falls watershed (17158.6 ha) in Maryland for 1994 and 1999 to document fragmentation, deforestation, and reforestation. The watershed was divided into lower (urban core), middle (older suburbs), and upper (recent suburbs) subsections. Over the entire watershed a net of 264.5 of 4855.5 ha of tree-covered patches were converted to urban land use-125 new tree-covered patches were added through fragmentation, 4 were added through reforestation, 43 were lost through deforestation, and 7 were combined with an adjacent patch. In addition, 180 patches were reduced in size. In the urban core, deforestation continued with conversion to commercial land use. Because of the lack of vegetation, commercial land uses are problematic for both species conservation and derived ecosystem benefits. In the lower subsection, shape complexity increased for tree-covered patches less than 10 ha. Changes in shape resulted from canopy expansion, planted materials, and reforestation of vacant sites. In the middle and upper subsections, the shape index value for tree-covered patches decreased, indicating simplification. Density analyses of the subsections showed no change with respect to patch densities but pointed out the importance of small patches (≤5 ha) as "stepping stone" to link large patches (e. g., ≥100 ha). Using an urban forest effect model, we estimated, for the entire watershed, total carbon loss and pollution removal, from 1994 to 1999, to be 14,235,889.2 kg and 13,011.4 kg, respectively due to urban land-use conversions.

The past, present and future of carbon labelling for construction materials – a review

Global climate change is one of the most significant environmental issues that can harm human development. One central issue for the building and construction industry to address global climate change is the development of a credible and meaningful way to measure greenhouse gas (GHG) emissions. While Publicly Available Specification (PAS) 2050, the first international GHG standard, has been proven to be successful in standardizing the quantification process, its contribution to the management of carbon labels for construction materials is limited. With the recent publication of ISO 14067: Greenhouse gases – carbon footprint of products – requirements and guidelines for quantification and communication in May 2013, it is necessary for the building and construction industry to understand the past, present and future of the carbon labelling practices for construction materials. A systematic review shows that international GHG standards have been evolving in terms of providing additional guidance on communication and comparison, as well as less flexibility on the use of carbon labels. At the same time, carbon labelling schemes have been evolving on standardization and benchmarking. In addition, future actions are needed in the aspect of raising consumer awareness, providing benchmarking, ensuring standardization and developing simulation technologies in order for carbon labelling schemes for construction materials to provide credible, accurate and transparent information on GHG emissions.

Teaching fractions to adult learners enrolled in a civil construction course : knowledge, action and materials action in tandem

This paper investigates the teaching and learning of fractions to Indigenous adult learners in a Civil Construction Certificate Course. More specifically it explores why the use of materials is critical to building knowledge and understanding. This focus is important for two reasons. First, it allows for considerations of a trainer’s approach for teaching fractions and, second it provides insights into how adult learners can be supported with representing their practical experiences of fractions to make generalisation thus building on their knowledge and learning experiences. The paper draws on teaching episodes from an Australian Research Council funded Linkage project that investigates how mathematics is taught and learned in Certificate Courses, here, Certificate 11 in Civil Construction. Action research and decolonising methods (Smith, 1999) were used to conduct the research. Video excerpts which feature one trainer and three students are analysed and described. Findings from the data indicate that adult learners need to be supported with materials to assist with building their capacity to know and apply understandings of fractions in a range of contexts, besides construction. Without materials and where fractions are taught via pen and paper tasks, students are less likely to retain and apply fraction ideas to their Certificate Course. Further they are less likely to understand decimals because of limited understanding of fractions.

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.

Bisphenol A degradation enhanced by air bubbles via advanced oxidation using in situ generated ferrous ions from nano zero-valent iron/palygorskite composite materials

Novel nano zero-valent iron/palygorskite composite materials prepared by evaporative and centrifuge methods are tested for the degradation of bisphenol A in an aqueous medium. A systematic study is presented which showed that nano zero-valent iron material has little effect on bisphenol A degradation. When hydrogen peroxide was added to initiate the reaction, some percentage of bisphenol A removal (∼20%) was achieved; however, with the aid of air bubbles, the percentage removal can be significantly increased to ∼99%. Compared with pristine nano zero-valent iron and commercial iron powder, nano zero-valent iron/palygorskite composite materials have much higher reactivity towards bisphenol A and these materials are superior as they have little impact on the solution pH. However, for pristine nano zero-valent iron, it is difficult to maintain the reaction system at a favourable low pH which is a key factor in maintaining high bisphenol A removal. All materials were characterized by X-ray diffraction, scanning electron microscopy, elemental analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The optimum conditions were obtained based on a series of batch experiments. This study has extended the application of nano zero-valent iron/palygorskite composites as effective materials for the removal of phenolic compounds from the environment.

Preparation and characterization of composites from starch with sugarcane bagasse nanofibres

This paper reports on the results of using unbleached sugar cane bagasse nanofibres (average diameter 26.5 nm; aspect ratio 247 assuming a dry fibre density of 1,500 kg/m3) to improve the physico-chemical properties of starch-based films. The addition of bagasse nanofibres (2.5 to 20 wt%) to modified potato starch (i.e. soluble starch) reduced the moisture uptake by up to 17 % at 58 % relative humidity. The film’s tensile strength and Young’s modulus increased by up to 100 % (3.1 to 6.2 MPa) and 300 % (66.3 to 198.3 MPa) respectively with 10 and 20 wt% fibre addition. However, the strain at yield dropped by 50 % for the film containing 10 wt% fibre. Models for composite materials were used to account for the strong interactions between the nanofibres and the starch matrix. The storage and loss moduli as well as the glass transition temperature (Tg) obtained from dynamic mechanical thermal analysis, were increased with the starch-nanofibre films indicating decreased starch chain mobility due to the interacting effect of the nanofibres. Evidence of the existence of strong interactions between the starch matrix and the nanofibres was revealed from detailed Fourier transform infra-red and scanning electron microscopic evaluation.