Key attributes underpinning different markup decision between public and private projects : a China study

In the construction industry, contractors have to improve the efficiency of markup decision-making to survive from fierce business competition. The effect of client type on markup decision has been aware in previous studies and contractors are advocated to take account of decision factors properly when they are confronted with different types of projects. Nevertheless, the rationales behind the inclusion of different factors in markup decision-making for different projects sustain unknown. In this study, fifty-three factors were identified after extensive literature review and interviews with professionals. The identified factors were afterwards grouped under the headings of nine attributes and compiled in a questionnaire for survey in China. Using the Hotelling’s T-square test, it is found that three attributes (i.e., project characteristic, client characteristic, and macro condition) can explain the effect of client type on contractors’ markup decision. The research findings provide useful insights into the cognition of bid pricing as well as the improvement of bidding efficiency. While the research works were situated in China, contractors in other countries could benefit from the research findings in a similar vein.

Controlling whole blood activation and resultant clot properties on various material surfaces : a possible therapeutic approach for enhancing bone healing

Injured bone initiates the healing process by forming a blood clot at the damaged site. However, in severe damage, synthetic bone implants are used to provide structural integrity and restore the healing process. The implant unavoidably comes into direct contact with whole blood, leading to a blood clot formation on its surface. Despite this, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Surface chemistry of a biomaterial is a crucial property in mediating blood-biomaterials interactions, and hence the formation of the resultant blood clot. Surfaces presenting mixtures of functional groups carboxyl (–COOH) and methyl (–CH3) have been shown to enhance platelet response and coagulation activation, leading to the formation of fibrin fibres. In addition, it has been shown that varying the compositions of these functional groups and the length of alkyl groups further modulate the immune complement response. In this study, we hypothesised that a biomaterial surface with mixture of –COOH/–CH3(methyl), –CH2CH3 (ethyl) or –(CH2)3CH3 (butyl) groups at different ratios would modulate blood coagulation and complement activation, and eventually tailor the structural and functional properties of the blood clot formed on the surface, which subsequently impacts new bone formation. Firstly, we synthesised a series of materials composed of acrylic acid (AA), and methyl (MMA), ethyl (EMA) or butyl methacrylates (BMA) at different ratios and coated on the inner surfaces of incubation vials. Our surface analysis showed that the amount of –COOH groups on the surface coatings was lower than the ratios of AA prepared in the materials even though the surface content of –COOH groups increased with increasing in AA ratios. It was indicated that the surface hydrophobicity increased with increasing alkyl chain length: –CH 3 > –CH2CH3 > –(CH2)3CH3, and decreased with increasing –COOH groups. No significant differences in surface hydrophobicity was found on surfaces with –CH3 and –CH2CH3 groups in the presence of –COOH groups. The material coating was as smooth as uncoated glass and without any major flaws. The average roughness of material-coated surface (3.99 ± 0.54 nm) was slightly higher than that of uncoated glass surface (2.22 ± 0.29 nm). However, no significant differences in surface average roughness was found among surfaces with the same functionalities at different –COOH ratios nor among surfaces with different alkyl groups but the same –COOH ratios. These suggested that the surface functional groups and their compositions had a combined effect on modulating surface hydrophobicity but not surface roughness. The second part of our study was to investigate the effect of surface functional groups and their compositions on blood cascade activation and structural properties of the formed clots. It was found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/–CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of activation. Moreover, all material-coated surfaces markedly reduced the complement activation compared to uncoated glass surfaces, and the pattern of complement activation was entirely similar to that of surface-induced coagulation, suggesting there is an interaction between two cascades. The clots formed on material-coated surfaces had thicker fibrin with a tighter network at the exterior when compared to uncoated glass surfaces. Compared to the clot exteriors, thicker fibrins with a loose network were found in clot interiors. Coated surfaces resulted in more rigid clots with a significantly slower fibrinolysis after 1 h of lysis when compared to uncoated glass surfaces. Significant differences in fibrinolysis after 1 h of lysis among clots on material-coated surfaces correlated well with the differences in fibrin thickness and density at clot exterior. In addition, more growth factors were released during clot formation than during clot lysis. From an intact clot, there was a correlation between the amount of PDGF-AB release and fibrin density. Highest amount of PDGF-AB was released from clots formed on surfaces with 40% –COOH/60% –CH 3 (i.e. 65MMA). During clot lysis, the release of PDGF-AB also correlated with the fibrinolytic rate while the release of TGF-â1 was influenced by the fibrin thickness. This suggested that different clot structures led to different release profiles of growth factors in clot intact and degrading stages. We further validated whether the clots formed on material-coatings provide the microenvironment for improved bone healing by using a rabbit femoral defect model. In this pilot study, the implantation of clots formed on 65MMA coatings significantly increased new bone formation with enhanced chondrogenesis, osteoblasts activity and vascularisation, but decreased inflammatory macrophage number at the defects after 4 weeks when compared to commercial bone grafts ChronOSTM â-TCP granules. Empty defects were observed when blood clot formation was inhibited. In summary, our study demonstrated that surface functional groups and their relative ratios on material coatings synergistically modulate activation of blood cascades, resultant fibrin architecture, rigidity, susceptibility to fibrinolysis as well as growth factor release of the formed clots, which ultimately alter the healing microenvironment of injured bones.

National survey of viruses in pastures of subterranean clover. II. Statistical methodology for large scale quantitative ELISA

Statistical methodology was applied to a survey of time-course incidence of four viruses (alfalfa mosaic virus, clover yellow vein virus, subterranean clover mottle virus and subterranean clover red leaf virus) in improved pastures in southern regions of Australia. -from Authors

National survey of viruses in pastures of subterranean clover. I. Incidence of four viruses assessed by ELISA

A nationwide survey was made of the time-course incidence of alfalfa mosaic virus (AMV), clover yellow vein virus (CYVV), subterranean clover mottle virus (SCMoV) and subterranean clover red leaf virus (SCRLV) in improved pastures in southern regions of Australia. Averaged over all states, the highest mean incidence recorded for samples infected with individual viruses in either winter or spring was 9.4% for AMV, 5.7% for CYVV, 10.9% for SCMoV and 7.5% for SCRLV. For AMV and SCRLV, there was an increasing trend from spring 1984 to spring 1986. A similar increasing trend for SCMoV was more evident in winter than in spring. For CYVV, no time-course pattern was evident. Results support the proposition that viruses contribute significantly to "clover-decline', a well-known problem in pastures of Trifolium subterraneum. -from Authors

Stimulation of osteogenic and angiogenic ability of cells on polymers by pulsed laser deposition of uniform akermanite-glass nanolayer

Polymer biomaterials have been widely used for bone replacement/regeneration because of their unique mechanical properties and workability. Their inherent low bioactivity makes them lack osseointegration with host bone tissue. For this reason, bioactive inorganic particles have been always incorporated into the matrix of polymers to improve their bioactivity. However, mixing inorganic particles with polymers always results in inhomogeneity of particle distribution in polymer matrix with limited bioactivity. This study sets out to apply the pulsed laser deposition (PLD) technique to prepare uniform akermanite (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non-degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to improve their surface osteogenic and angiogenic activity. The results show that a uniform nanolayer composed of amorphous AKT particles (∼30nm) of thickness 130nm forms on the surface of both PSU and PDLLA films with the PLD technique. The prepared AKT-PSU and AKT-PDLLA films significantly improved the surface roughness, hydrophilicity, hardness and apatite mineralization, compared with pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively enhance the alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films. Furthermore, AKT nanocoatings on two polymers improve the attachment, proliferation, VEGF secretion and expression of proangiogenic factors and their receptors of human umbilical vein endothelial cells (HUVEC). The results suggest that PLD-prepared bioceramic nanocoatings are very useful for enhancing the physicochemical, osteogenic and angiogenic properties of both degradable and non-degradable polymers for application in bone replacement/regeneration.

Periprosthetic fracture torque for short versus standard cemented hip stems : an experimental in vitro study

In an attempt to preserve proximal femoral bone stock and achieve a better fit in smaller femora, especially in the Asian population, several new shorter stem designs have become available. We investigated the torque to periprosthetic femoral fracture of the Exeter short stem compared with the conventional length Exeter stem in a Sawbone model. 42 stems; 21 shorter and 21 conventional stems both with three different offsets were cemented in a composite Sawbone model and torqued to fracture. Results showed that Sawbone femurs break at a statistically significantly lower torque to failure with a shorter compared to conventional length Exeter stem of the same offset. Both standard and short stem designs are safe to use as the torque to failure is 7-10 times that seen in activities of daily living.

Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Design, characterisation and in vivo testing of a new, adjustable stiffness, external fixator for the rat femur

Very little is known about the infl uence of the mechanical environment on the healing of large segmental defects. This partly reflects the lack of standardised, well characterised technologies to enable such studies. Here we report the design, construction and characterisation of a novel external fixator for use in conjunction with rat femoral defects. This device not only imposes a predetermined axial stiffness on the lesion, but also enables the stiffness to be changed during the healing process. The main frame of the fi xator consists of polyethylethylketone with titanium alloy mounting pins. The stiffness of the fi xator is determined by interchangeable connection elements of different thicknesses. Fixators were shown to stabilise 5 mm femoral defects in rats in vivo for at least 8 weeks during unrestricted cage activity. No distortion or infections, including pin infections, were noted. The healing process was simulated in vitro by inserting into a 5 mm femoral defect, materials whose Young’s moduli approximated those of the different tissues present in regenerating bone. These studies confirmed that, although the external fixator is the major determinant of axial stiffness during the early phase of healing, the regenerate within the lesion subsequently dominates this property. There is much clinical interest in altering the mechanics of the defect to enhance bone healing. Our data suggest that, if alteration of the mechanical environment is to be used to modulate the healing of large segmental defects, this needs to be performed before the tissue properties become dominant.

Ability of recombinant human bone morphogenetic protein 2 to enhance bone healing in the presence of tobramycin : evaluation in a rat segmental defect model

Objective To determine whether locally applied tobramycin influences the ability of recombinant human bone morphogenetic protein 2 (rhBMP-2) to heal a segmental defect in the rat femur. Methods The influence of tobramycin on the osteogenic differentiation of mesenchymal stem cells was first evaluated in vitro. For the subsequent, in vivo experiments, a 5-mm segmental defect was created in the right femur of each of 25 Sprague-Dawley rats and stabilized with an external fixator and four Kirschner wires. Rats were divided in four groups: empty control, tobramycin (11 mg)/absorbable collagen sponge, rhBMP-2 (11 μg)/absorbable collagen sponge, and rhBMP-2/absorbable collagen sponge with tobramycin. Bone healing was monitored by radiography at 3 and 8 weeks. Animals were euthanized at 8 weeks and the properties of the defect were compared with the intact contralateral femur. Bone formation in the defect region was assessed by dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing. Results Tobramycin exerted a dose-dependent inhibition of alkaline phosphatase induction and calcium deposition by mesenchymal stem cells cultured under osteogenic conditions. The inhibition was reversed in the presence of 500 ng/mL of rhBMP-2. Segmental defects in the rat femora failed to heal in the absence of rhBMP-2. Tobramycin exerted no inhibitory effects on the ability of rhBMP-2 to heal these defects and increased the bone area of the defects treated with rhBMP-2. Data obtained from all other parameters of healing, including dual-energy x-ray absorptiometry, microcomputed tomography, histology, and mechanical testing, were unaffected by tobramycin. Conclusions Although our in vitro results suggested that tobramycin inhibits the osteogenic differentiation of mesenchymal stem cells, this could be overcome by rhBMP-2. Tobramycin did not impair the ability of rhBMP-2 to heal critical-sized femoral defects in rats. Indeed, bone area was increased by nearly 20% in the rhBMP-2 group treated with tobramycin. This study shows that locally applied tobramycin can be used in conjunction with rhBMP-2 to enhance bone formation at fracture sites.

Mice lacking β-Adrenergic receptors have increased bone mass but are not protected from deleterious skeletal effects of ovariectomy

Activation of β2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether β-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of β-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known β-adrenergic receptors (β-less). Body weight, percent fat, and bone mineral density were significantly higher in male β-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in β-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult β-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male β-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in β-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in β-less compared with WT mice from 8–16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in β-less and WT mice. Altogether, these data indicate that absence of β-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling.

Revascularization and tissue regeneration of an empty root canal space is enhanced by a direct blood supply and stem cells

Background Regenerative endodontics is an innovative treatment concept aiming to regenerate pulp, dentin and root structures. In the diseased or necrotic tooth, the limitation in vascular supply renders successful tissue regeneration/generation in a whole tooth challenging. The aim of this study is to evaluate the ability of vascularized tissue to develop within a pulpless tooth using tissue engineering techniques. Materials and methods A pulpless tooth chamber, filled with collagen I gel containing isolated rat dental pulp cells (DPC) and angiogenic growth factors, was placed into a hole created in the femoral cortex or into its own tooth socket, respectively. The gross, histological and biochemical characteristics of the de novo tissue were evaluated at 4 and 8weeks post-transplantation. Results Tooth revascularization and tissue generation was observed only in the femur group, confirming the important role of vascular supply in tissue regeneration. The addition of cells and growth factors significantly promoted connective tissue production in the tooth chamber. Conclusion Successful revascularization and tissue regeneration in this model demonstrate the importance of a direct vascular supply and the advantages of a stem cell approach. © 2012 John Wiley & Sons A/S.

Nb2O5 Schottky based ethanol vapour sensors : effect of metallic catalysts

The aim of this paper is to compare the performances of the highly porous Nb2O5 Schottky based sensors formed using different catalytic metals for ethanol vapour sensing. The fabricated sensors consist of a fairly ordered nano-vein like porous Nb2O5 prepared via an elevated temperature anodization method. Subsequently, Pt, Pd and Au were sputtered as both Schottky contacts and catalysts for the comparative studies. These metals are chosen as they have large work functions in comparison to the electron affinity of the anodized Nb2O5. It is demonstrated that the device based on Pd/Nb2O5 Schottky contact has the highest sensitivity amongst the developed sensors. The sensing behaviors were studied in terms of the Schottky barrier height variations and properties of the metal catalysts.

Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development

Objective To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA). Methods OA was surgically induced in the knees of MMP-13-knockout mice and wild-type mice, and mice were compared. Histologic scoring of femoral and tibial cartilage aggrecan loss (0-3 scale), erosion (0-7 scale), and chondrocyte hypertrophy (0-1 scale), as well as osteophyte size (0-3 scale) and maturity (0-3 scale) was performed. Serial sections were stained for type X collagen and the MMP-generated aggrecan neoepitope DIPEN. Results Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (P < 0.01) and tibial cartilage erosion increased with time (P < 0.05) in wild-type mice. Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (P < 0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks. There was less tibial cartilage erosion in knockout mice than in wild-type mice at 8 weeks (P < 0.02). Cartilaginous osteophytes were larger in knockout mice at 4 weeks (P < 0.01), but by 8 weeks osteophyte maturity and size were no different from those in wild-type mice. Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both wild-type and knockout mouse joints. Conclusion Our findings indicate that structural cartilage damage in a mouse model of OA is dependent on MMP-13 activity. Chondrocyte hypertrophy is not regulated by MMP-13 activity in this model and does not in itself lead to cartilage erosion. MMP-13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP-13 inhibitors.

The role of biological extracellular matrix scaffolds in vascularized three-dimensional tissue growth in vivo

An in vivo murine vascularized chamber model has been shown to generate spontaneous angiogenesis and new tissue formation. This experiment aimed to assess the effects of common biological scaffolds on tissue growth in this model. Either laminin-1, type I collagen, fibrin glue, hyaluronan, or sea sponge was inserted into silicone chambers containing the epigastric artery and vein, one end was sealed with adipose tissue and the other with bone wax, then incubated subcutaneously. After 2, 4, or 6 weeks, tissue from chambers containing collagen I, fibrin glue, hyaluronan, or no added scaffold (control) had small amounts of vascularized connective tissue. Chambers containing sea sponge had moderate connective tissue growth together with a mild "foreign body" inflammatory response. Chambers containing laminin-1, at a concentration 10-fold lower than its concentration in Matrigel™, resulted in a moderate adipogenic response. In summary, (1) biological hydrogels are resorbed and gradually replaced by vascularized connective tissue; (2) sponge-like matrices with large pores support connective tissue growth within the pores and become encapsulated with granulation tissue; (3) laminin-containing scaffolds facilitate adipogenesis. It is concluded that the nature and chemical composition of the scaffold exerts a significant influence on the amount and type of tissue generated in this in vivo chamber model.

BM18 : a novel androgen-dependent human prostate cancer xenograft model derived from a bone metastasis

BACKGROUND Androgen-dependent prostate cancer (PrCa) xenograft models are required to study PrCa biology in the clinically relevant in vivo environment. METHODS Human PrCa tissue from a femoral bone metastasis biopsy (BM18) was grown and passaged subcutaneously through male severe combined immune-deficient (SCID) mice. Human mitochondria (hMt), prostate specific antigen (PSA), androgen receptor (AR), cytokeratin-18 (CK-18), pan-cytokeratin, and high molecular weight-cytokeratin (HMW-CK) were assessed using immunohistochemistry (IHC). Surgical castration was performed to examine androgen dependence. Serum was collected pre- and post-castration for monitoring of PSA levels. RESULTS: BM18 stained positively for hMt, PSA, AR, CK-18, pan keratin, and negatively for HMW-CK, consistent with the staining observed in the original patient material. Androgen-deprivation induced tumor regression in 10/10 castrated male SCID mice. Serum PSA levels positively correlated with BM18 tumor size. CONCLUSIONS BM18 expresses PSA and AR, and rapidly regresses in response to androgen withdrawal. This provides a new clinically significant PrCa model for the study of androgen-dependent growth.