Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate

The osteoimmunomodulatory property of bone biomaterials is a vital property determining the in vivo fate of the implants. Endowing bone biomaterials with favorable osteoimmunomodulatory properties is of great importance in triggering desired immune response and thus supports the bone healing process. Magnesium (Mg) has been recognized as a revolutionary metal for applications in orthopedics due to it being biodegradable, biocompatible, and having osteoconductive properties. However, Mg's high rate of degradation leads to an excessive inflammatory response and this has restricted its application in bone tissue engineering. In this study, β-tricalcium phosphate (β-TCP) was used to coat Mg scaffolds in an effort to modulate the detrimental osteoimmunomodulatory properties of Mg scaffolds, due to the reported favorable osteoimmunomodulatory properties of β-TCP. It was noted that macrophages switched to the M2 extreme phenotype in response to the Mg-β-TCP scaffolds, which could be due to the inhibition of the toll like receptor (TLR) signaling pathway. VEGF and BMP2 were significantly upregulated in the macrophages exposed to Mg-β-TCP scaffolds, indicating pro-osteogenic properties of macrophages in β-TCP modified Mg scaffolds. This was further demonstrated by the macrophage-mediated osteogenic differentiation of bone marrow stromal cells (BMSCs). When BMSCs were stimulated by conditioned medium from macrophages cultured on Mg-β-TCP scaffolds, osteogenic differentiation of BMSCs was significantly enhanced; whereas osteoclastogenesis was inhibited, as indicated by the downregualtion of MCSF, TRAP and inhibition of the RANKL/RANK system. These findings suggest that β-TCP coating of Mg scaffolds can modulate the scaffold's osteoimmunomodulatory properties, shift the immune microenvironment towards one that favors osteogenesis over osteoclastogenesis. Endowing bone biomaterials with favorable osteoimmunomodulatory properties can be a highly valuable strategy for the development or modification of advanced bone biomaterials.

6 versus 12 month performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction Well-designed biodegradable scaffolds in combination with bone growth factors offer a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a large preclinical animal model. Methods Twelve sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion assessments were performed via high resolution clinical computed tomography and histological evaluation were undertaken at six (n=6) and twelve (n=6) months post-surgery using the Sucato grading system (Sucato et al. 2004). Results The computed tomography fusion grades of the 6- and 12- months in the rhBMP-2 plus PCL- based scaffold group were 1.9 and 2.1 respectively, in the autograft group 1.9 and 1.3 respectively, and in the scaffold alone group 0.9 and 1.17 respectively. There were no statistically significant differences in the fusion scores between 6- and 12- month for the rhBMP plus PCL- based scaffold or PCL – based scaffold alone group however there was a significant reduction in scores in the autograft group. These scores were seen to correlate with histological evaluations of the respective groups. Conclusions The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post-surgery.

A disaggregate discrete choice model of transportation demand by elderly and disabled people in rural Virginia

This paper uses a correlated multinomial logit model and a Poisson regression model to measure the factors affecting demand for different types of transportation by elderly and disabled people in rural Virginia. The major results are: (a) A paratransit system providing door-to-door service is highly valued by transportation-handicapped people; (b) Taxis are probably a potential but inferior alternative even when subsidized; (c) Buses are a poor alternative, especially in rural areas where distances to bus stops may be long; (d) Making buses handicap-accessible would have a statistically significant but small effect on mode choice; (e) Demand is price inelastic; and (f) The total number of trips taken is insensitive to mode availability and characteristics. These results suggest that transportation-handicapped people take a limited number of trips. Those they do take are in some sense necessary (given the low elasticity with respect to mode price or availability). People will substitute away from relying upon others when appropriate transportation is available, at least to some degree. But such transportation needs to be flexible enough to meet the needs of the people involved.

Effect of doping with Co and/or Cu on electronic structure and optical properties of ZnO

This paper reports on ab initio numerical simulations of the effect of Co and Cu dopings on the electronic structure and optical properties of ZnO, pursued to develop diluted magnetic semiconductors vitally needed for spintronic applications. The simulations are based upon the Perdew-Burke-Enzerh generalized gradient approximation on the density functional theory. It is revealed that the electrons with energies close to the Fermi level effectively transfer only between Cu and Co ions which substitute Zn atoms, and are located in the neighbor sites connected by an O ion. The simulation results are consistent with the experimental observations that addition of Cu helps achieve stable ferromagnetism of Co-doped ZnO. It is shown that simultaneous insertion of Co and Cu atoms leads to smaller energy band gap, redshift of the optical absorption edge, as well as significant changes in the reflectivity, dielectric function, refractive index, and electron energy loss function of ZnO as compared to the doping with either Co or Cu atoms. These highly unusual optical properties are explained in terms of the computed electronic structure and are promising for the development of the next-generation room-temperature ferromagnetic semiconductors for future spintronic devices on the existing semiconductor micromanufacturing platform.

Cutting the Gordian knot of futility : a case for law reform on unilateral withholding and withdrawal of potentially life-sustaining treatment

In this paper, we propose law reform with respect to the unilateral withholding or withdrawal of potentially life-sustaining treatment in Australia and New Zealand. That is, where a doctor withholds or withdraws potentially life-sustaining treatment without consent from a patient or a patient’s substitute decision-maker (where the patient lacks capacity), or authorisation from a court or tribunal, or by operation of a statute or justifiable government or institutional policy. Our proposal is grounded in the core values that do (or should) underpin a regulatory framework on an issue such as this; these values are drawn from existing commitments made by Australia and New Zealand through legislation, the common law, and conventions and treaties. It is also grounded in a critical review of the law on unilateral withholding and withdrawal as well as the legal context within which this issue sits in Australasia. We argue that the current law is inconsistent with the core values and develop a proposal for a legal response to this issue that more closely aligns with the core values it is supposed to serve.

Withholding and withdrawing life-sustaining medical treatment

• At common law, a competent adult can refuse life-sustaining medical treatment, either contemporaneously or through an advance directive which will operate at a later time when the adult’s capacity is lost. • Legislation in most Australian jurisdictions also provides for a competent adult to complete an advance directive that refuses life-sustaining medical treatment. • At common law, a court exercising its parens patriae jurisdiction can consent to, or authorise, the withdrawal or withholding of life-sustaining medical treatment from an adult or child who lacks capacity if that is in the best interests of the person. A court may also declare that the withholding or withdrawal of treatment is lawful. • Guardianship legislation in all jurisdictions allows a substitute decision-maker, in an appropriate case, to refuse life-sustaining medical treatment for an adult who lacks capacity. • In terms of children, a parent may refuse life-sustaining medical treatment for his or her child if it is in the child’s best interests. • While a refusal of life-sustaining medical treatment by a competent child may be valid, this decision can be overturned by a court. • At common law and generally under guardianship statutes, demand for futile treatment need not be complied with by doctors.

Linkages among the US energy futures markets

This study investigates the price linkage among the US major energy sources, considering structural breaks in time series, to provide information for diversifying the US energy sources. We find that only a weak linkage sustains among crude oil, gasoline, heating oil, coal, natural gas, uranium and ethanol futures prices. This implies that the US major energy source markets are not integrated as one primary energy market. Our tests also reveal that uranium and ethanol futures prices have very weak linkages with other major energy source prices. This indicates that the US energy market is still at a stage where none of the probable alternative energy source markets are playing the role as substitute or complement markets for the fossil fuel energy markets.

Effect of Oil Price on Emissions Trading Market: VAR Analysis

In this study, we investigated the relationship of European Union carbon dioxide CO2 allowances EUAs prices and oil prices by employing a VAR analysis, Granger causality test and impulse response function. If oil price continues increasing, companies will decrease dependency on fossil fuels because of an increase in energy costs. Therefore, the price of EUAs may be affected by variations in oil prices if the greenhouse gases discharged by the consumption of alternative energy are less than that of fossil fuels. There are no previous studies that investigated these relationships. In this study, we analyzed eight types of EUAs EUA05 to EUA12 with a time series daily data set during 2005-2007 collected from a European Climate Exchange time series data set. Differentiations in these eight types were redemption period. We used the New York Mercantile Exchange light sweet crude price as an oil price. From our examination, we found that only the EUA06 and EUA07 types of EUAs Granger-cause oil prices and vice versa and other six types of EUAs do not Granger-cause oil price. These results imply that the earlier redemption period types of EUAs are more sensitive to oil price. In employing the impulse response function, the results showed that a shock to oil price has a slightly positive effect on all types of EUAs for a very short period. On the other hand, we found that a shock to price of EUA has a slightly negative effect on oil price following a positive effect in only EUA06 and EUA07 types. Therefore, these results imply that fluctuations in EUAs prices and oil prices have little effect on each other. Lastly, we did not consider the substitute energy prices in this study, so we plan to include the prices of coal and natural gas in future analyses.

Non-separability and substitutability among water pollutants : evidence from India

The design and implementation of environmental policy often involve more than one pollutant, and must consider pollution as a byproduct of the production of marketable output. In this paper, we test the implicit assumption in the empirical literature that (1) production of marketable output, pollution and abatement are separable, and (2) different pollutants can be abated separately. Using unique plant-level data in India, we reject the null hypotheses of separability between marketable output and pollutants, and between different pollutants. Firms must incur abatement costs for reducing pollution levels. In addition, complement and substitute relationships between water pollutants are demonstrated with statistical significance.

Health and guardianship law : guardianship and administration application in the matter of MDC [2014] QCAT 338

The recent decision of the Queensland Civil and Administrative Tribunal (QCAT) in Guardianship and administration application in the matter of MDC [2014] QCAT 338, provides an important ruling on the limits of who can be appointed as an enduring power of attorney under the Powers of Attorney Act 1998 (Qld). In particular, the tribunal adopted a broad interpretation of the term "health provider" when considering the limits on who can be appointed as an enduring power of attorney under the legislation...

Longitudinal performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in large preclinical animal model : 6- versus 12 months

There is strong current interest in the use of biodegradable scaffolds in combination with bone growth factors as a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a preclinical ovine thoracic spine. The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post surgery.

Effective public speaking for the Australian curriculum

Public speaking has been with us since the great orators of the cultural heritage tradition and is by no means a dying art. There is no substitute for the human voice in real time, and technology-delivered speeches cannot really move an audience in precisely ways that effective, live speaking can. Many teachers go to history to access models such as the great Martin Luther King’s “I have a dream” speech, or Winston Churchill’s call to battle. Most of us can recall Kevin Rudd’s historical apology to Indigenous Australia’s stolen generation, and more recently Noel Pearson’s moving eulogy delivered to a mourners at Gough Whitlam’s funeral. We are fortunate now to be able to access speeches from more recent history, closer to home and in our own accents through online repositories. This paper is, in part, written as a guide for pre-service teachers who did not learn this at school, and experienced teachers may also find it useful.

Mathematical models of calcium and tight junctions in normal and reconstructed epidermis

This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.

MATLAB/Simulink simulation and C2000 code generation model for a grid-interactive 3-phase 4-wire inverter

This work is a MATLAB/Simulink model of a controller for a three-phase, four-wire, grid-interactive inverter. The model provides capacity for simulating the performance of power electroinic hardware, as well as code generation for an embedded controller. The implemented hardware topology is a three-leg bridge with a neutral connection to the centre-tap of the DC bus. An LQR-based current controller and MAF-based phase detector are implemented. The model is configured for code generation for a Texas Instruments TMS320F28335 Digital Signal Processor (DSP).

Palliative care and other physicians’ knowledge, attitudes and practice relating to the law on withholding/withdrawing life-sustaining treatment: Survey results

Background: To effectively care for people who are terminally ill, including those without decision-making capacity, palliative care physicians must know and understand the legal standing of Advance Care Planning (ACP) in their jurisdiction of practice. This includes the use of advance directives/living wills (ADs) and substitute decision-makers (SDMs) who can legally consent to or refuse treatment if there is no valid AD. Aim: The study aimed to investigate the knowledge, attitudes and practices of medical specialists most often involved in end-of-life care in relation to the law on withholding/ withdrawing life-sustaining treatment (WWLST) from adults without decision-making capacity. Design/participants: A pre-piloted survey was posted to specialists in palliative, emergency, geriatric, renal and respiratory medicine, intensive care and medical oncology in three Australian States. Surveys were analysed using SPSS20 and SAS 9.3. Results: The overall response rate was 32% (867/2702); 52% from palliative care specialists. Palliative Care specialists and Geriatricians had significantly more positive attitudes towards the law (χ242 = 94.352; p < 0.001) and higher levels of knowledge about the WWLST law (χ27 = 30.033; p < 0.001), than did the other specialists, while still having critical gaps in their knowledge. Conclusions: A high level of knowledge of the law is essential to ensure that patients’ wishes and decisions, expressed through ACP, are respected to the maximum extent possible within the law, thereby according with the principles and philosophy of palliative care. It is also essential to protect health professionals from legal action resulting from unauthorised provision or removal of treatment.