A process-oriented approach to supporting Off-site Manufacture in construction projects

It is well-known that the use of off-site manufacture (OSM) techniques can assist in timely completion of a construction project though the utilisation of such techniques may have other disadvantages. Currently, OSM uptake within the Australian construction industry is limited. To successfully incorporate OSM practices within a construction project, it is crucial to understand the impact of OSM adoption on the processes used during a construction project. This paper presents how a systematic process-oriented approach may be able to support OSM utilisation within a construction project. Process modelling, analysis and automation techniques which are well-known within the Business Process Management (BPM) discipline have been applied to develop a collection of construction process models that represent the end-to-end generic construction value chain. The construction value chain enables researchers to identify key activities, resources, data, and stakeholders involved in construction processes in each defined construction phase. The collection of construction process models is then used as a basis for identification of potential OSM intervention points in collaboration with domain experts from the Australian construction industry. This ensures that the resulting changes reflect the needs of various stakeholders within the construction industry and have relevance in practice. Based on the input from the domain experts, these process models are further refined and operational requirements are taken into account to develop a prototype process automation (workflow) system that can support and coordinate OSM-related process activities. The resulting workflow system also has the potential to integrate with other IT solutions used within the construction industry (e.g., BIM, Acconex). As such, the paper illustrates the role that process-oriented thinking can play in assisting OSM adoption within the industry.

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Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted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).

An additive model for spatio-temporal smoothing of cancer mortality rates

In this paper, a Bayesian hierarchical model is used to anaylze the female breast cancer mortality rates for the State of Missouri from 1969 through 2001. The logit transformations of the mortality rates are assumed to be linear over the time with additive spatial and age effects as intercepts and slopes. Objective priors of the hierarchical model are explored. The Bayesian estimates are quite robustness in terms change of the hyperparamaters. The spatial correlations are appeared in both intercepts and slopes.

On the importance of an acid additive in the synthesis of pyrido[1,2-a]benzimidazoles by direct copper-catalyzed amination

Pyrido[1,2-a]benzimidazoles1, 2a are interesting compounds both from the viewpoint of medicinal chemistry2–7 (solubility,7 DNA intercalation3) and materials chemistry8 (fluorescence). Of note among the former is the antibiotic drug Rifaximin,5 which contains this heteroaromatic core. The classical synthetic approach for the assembly of pyrido[1,2-a]benzimidazoles is by [3+3] cyclocondensation of benzimidazoles containing a methylene group at C2 with appropriate bielectrophiles.2a However, these procedures are often low-yielding, involve indirect/lengthy sequences, and/or provide access to a limited range of products, primarily providing derivatives with substituents located on the pyridine ring (A ring, Scheme 1).2–4 Theoretically, a good alternative synthetic method for the synthesis of pyrido[1,2-a]benzimidazoles with substituents in the benzene ring (C ring) should be accessible by intramolecular transition-metal-catalyzed CN bond formation in N-(2-chloroaryl)pyridin-2-amines, based on chemistry recently developed in our research group.9 These substrates themselves are easily available through SNAr or selective Pd-catalyzed amination10 of 2-chloropyridine with 2-chloroanilines.11 If a synthetic procedure that eliminated the need for preactivation of the 2-position of the 2-chloroarylamino entity could be developed, this would be even more powerful, as anilines are more readily commercially available than 2-chloroanilines. Therefore the synthesis of pyrido[1,2-a]benzimidazoles (4) by a transition-metal-catalyzed intramolecular CH amination approach from N-arylpyridin-2-amines (3) was explored (Scheme 1).

In vitro and in vivo assessment of bioactive composite scaffolds fabricated via additive manufacturing technology

Additive manufacturing (AM) technology was implemented together with new composite material comprising a synthetic materials, namely, polycaprolactone and bioactive glass with the ultimate aim of the production of an off-the-shelf composite bone scaffold product with superior bone regeneration capacity in a cost effective manner. Our studies indicated that the composite scaffolds have huge potential in promoting bone regeneration. It is our contention that owing to the fruits of such innovative efforts, the field of bone regeneration can metamorphose into a technology platform that allows clinicians worldwide to create tissue-engineered bone with economies of scale in the years to come.

High-throughput bone and cartilage micropellet manufacture, followed by assembly of micropellets into biphasic osteochondral tissue

Engineered biphasic osteochondral tissues may have utility in cartilage defect repair. As bone-marrow-derived mesenchymal stem/stromal cells (MSC) have the capacity to make both bone-like and cartilage-like tissues, they are an ideal cell population for use in the manufacture of osteochondral tissues. Effective differentiation of MSC to bone-like and cartilage-like tissues requires two unique medium formulations and this presents a challenge both in achieving initial MSC differentiation and in maintaining tissue stability when the unified osteochondral tissue is subsequently cultured in a single medium formulation. In this proof-of-principle study, we used an in-house fabricated microwell platform to manufacture thousands of micropellets formed from 166 MSC each. We then characterized the development of bone-like and cartilage-like tissue formation in the micropellets maintained for 8–14 days in sequential combinations of osteogenic or chondrogenic induction medium. When bone-like or cartilage-like micropellets were induced for only 8 days, they displayed significant phenotypic changes when the osteogenic or chondrogenic induction medium, respectively, was swapped. Based on these data, we developed an extended 14-day protocol for the pre-culture of bone-like and cartilage-like micropellets in their respective induction medium. Unified osteochondral tissues were formed by layering 12,000 osteogenic micropellets and 12,000 chondrogenic micropellets into a biphasic structure and then further culture in chondrogenic induction medium. The assembled tissue was cultured for a further 8 days and characterized via histology. The micropellets had amalgamated into a continuous structure with distinctive bone-like and cartilage-like regions. This proof-of-concept study demonstrates the feasibility of micropellet assembly for the formation of osteochondral-like tissues for possible use in osteochondral defect repair.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD)". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC) each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

Biofabrication of customized bone grafts by combination of additive manufacturing and bioreactor knowhow

This study reports on an original concept of additive manufacturing for the fabrication of tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept towards the development of anatomically relevant TECs, this concept was utilized for the design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold device was investigated by micro-computed tomography and scanning electron microscopy confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as the inner architecture of the device can significantly impact the perfusion of fluid within the scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant importance for controlling the nutrition flow pattern within the scaffold and the bioreactor chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue development. The bioreactor/scaffold device was dynamically seeded with human primary osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human osteoblasts were observed homogenously distributed throughout the scaffold, and were viable for the six week culture period. This work demonstrates a novel application for additive manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility of the additive manufacturing technology platform developed, more complex culture systems can be fabricated which would contribute to the advances in customized and patient-specific tissue engineering strategies for a wide range of applications.

Development and characterisation of a new bioink for additive tissue manufacturing

Additive manufacturing forms a potential route towards economically viable production of cellular constructs for tissue engineering. Hydrogels are a suitable class of materials for cell delivery and 3D culture, but are generally unsuitable as construction materials. Gelatine-methacrylamide is an example of such a hydrogel system widely used in the field of tissue engineering, e.g. for cartilage and cardiovascular applications. Here we show that by the addition of gellan gum to gelatine-methacrylamide and tailoring salt concentrations, rheological properties such as pseudo-plasticity and yield stress can be optimised towards gel dispensing for additive manufacturing processes. In the hydrogel formulation, salt is partly substituted by mannose to obtain isotonicity and prevent a reduction in cell viability. With this, the potential of this new bioink for additive tissue manufacturing purposes is demonstrated.

Development and testing of an evaluation procedure for commercial manure additive products.

Manure additive products can be used to reduce odour emissions (OE) from livestock farms. The standardised evaluation of these manure additive products under specific farm conditions is important. In this study, the efficacy of a manure additive (WonderTreat(TM), CKLS, Inc., Hong-Kong) was assessed under Australian conditions utilising a combination of laboratory and field-scale evaluation techniques. As a first step, the efficacy of the manure additive was assessed in a laboratory-scale trial using a series of uniformly managed digesters and standard odour, liquor ammonia and hydrogen sulphide concentration measurement procedures. This showed that the addition of WonderTreat(TM) at the 'low dose rate' (LDR) (102.6 g m-2) used during the trial significantly, but only marginally (30%; P = 0.02) reduced the OE rate (mean 13.9 OU m-2 s-1) of anaerobic pig liquor relative to an untreated control (UC) (19.9 OU m-2 s-1). However, the 'high dose rate' (HDR) (205.3 g m-2) also assessed during the trial preformed similarly (19.7 OU m-2 s-1) to the UC. No statistically significant difference in the concentrations of a range of measured water quality variables at the 5% level was observed between the treatments or controls digesters. As a second step, a field-scale assessment of the manure additive was undertaken at a commercial piggery. Two piggery manure lagoons (each with approximately 2500 m2 surface area) were included in the study; one was treated with WonderTreat(TM) while the other was used as control. The efficacy of the treatment was assessed using olfactometric evaluation of odour samples collected from the surface of the pond using a dynamic wind tunnel and ancillary equipment. No statistically significant reduction in OE rate could be demonstrated (P = 0.35), partially due to the limited number of samples taken during the assessment. However, there was a numerical reduction in the average OE rate of the treatment pond (29 OU m-2 s-1 at 1 m s-1) compared to the control lagoon (38 OU m-2 s-1 at 1 m s-1).

SRDC-Manufacture of a new beverage base from sugar depleted cane juice

The overall objective of the proposed project is to increase profitability through application of membrane technology.