Access to high cost medicines in Australia: ethical perspectives

Access to "high cost medicines" through Australia's Pharmaceutical Benefits Scheme (PBS) is tightly regulated. It is inherently difficult to apply any criteria-based system of control in a way that provides a fair balance between efficient use of limited resources for community needs and equitable individual access to care. We suggest, in relation to very high cost medicines, that the present arrangements be re-considered in order to overcome potential inequities. The biological agents for the treatment of rheumatoid arthritis are used as an example by which to discuss the ethical issues associated with the current scheme. Consideration of ethical aspects of the PBS and similar programs is important in order to achieve the fairest outcomes for individual patients, as well as for the community

A complete MacWilliams theorem for convolutional codes

© 2014 IEEE. In this paper, we prove a MacWilliams identity for the weight adjacency matrices based on the constraint codes of a convolutional code (CC) and its dual. Our result improves upon a recent result by Gluesing-Luerssen and Schneider, where the requirement of a minimal encoder is assumed. We can also establish the MacWilliams identity for the input-parity weight adjacency matrices of a systematic CC and its dual. Most importantly, we show that a type of Hamming weight enumeration functions of all codewords of a CC can be derived from the weight adjacency matrix, which thus provides a connection between these two very different notions of weight enumeration functions in the convolutional code literature. Finally, the relations between various enumeration functions of a CC and its dual are summarized in a diagram. This explains why no MacWilliams identity exists for the free-distance enumerators

A geometric view on the generalized Proudman-Johnson and rr-Hunter-Saxton equations

We show that two families of equations, the generalized inviscid Proudman-Johnson equation, and the $r$-Hunter-Saxton equation (recently introduced by Cotter et al.) coincide for a certain range of parameters. This gives a new geometric interpretation of these Proudman-Johnson equations as geodesic equations of right invariant homogeneous $W^{1,r}$-Finsler metrics on the diffeomorphism group. Generalizing a construction of Lenells for the Hunter-Saxton equation, we analyze these equations using an isometry from the diffeomorphism group to an appropriate subset of real-valued functions. Thereby we show that the periodic case is equivalent to the geodesic equations on the $L^r$-sphere in the space of functions, and the non-periodic case is equivalent to a geodesic flow on a flat space. This allows us to give explicit solutions to these equations in the non-periodic case, and answer several questions of Cotter et al. regarding their limiting behavior

The LpL^p-Fisher-Rao metric and Amari-Cencov α\alpha-connections

We introduce a family of Finsler metrics, called the $L^p$-Fisher-Rao metrics $F_p$, for $p\in (1,\infty)$, which generalizes the classical Fisher-Rao metric $F_2$, both on the space of densities Dens$_+(M)$ and probability densities Prob$(M)$. We then study their relations to the Amari-\u{C}encov $\alpha$-connections $\nabla^{(\alpha)}$ from information geometry: on Dens$_+(M)$, the geodesic equations of $F_p$ and $\nabla^{(\alpha)}$ coincide, for $p = 2/(1-\alpha)$. Both are pullbacks of canonical constructions on $L^p(M)$, in which geodesics are simply straight lines. In particular, this gives a new variational interpretation of $\alpha$-geodesics as being energy minimizing curves. On Prob$(M)$, the $F_p$ and $\nabla^{(\alpha)}$ geodesics can still be thought as pullbacks of natural operations on the unit sphere in $L^p(M)$, but in this case they no longer coincide unless $p=2$. Using this transformation, we solve the geodesic equation of the $\alpha$-connection by showing that the geodesic are pullbacks of projections of straight lines onto the unit sphere, and they always cease to exists after finite time when they leave the positive part of the sphere. This unveils the geometric structure of solutions to the generalized Proudman-Johnson equations, and generalizes them to higher dimensions. In addition, we calculate the associate tensors of $F_p$, and study their relation to $\nabla^{(\alpha)}$

Investigation of polymer bonded magnetic materials for power conversion

Author name used in this publication: K. W. E. ChengAuthor name used in this publication: C. Y. TangAuthor name used in this publication: D. K. W. ChengAuthor name used in this publication: H. WuAuthor name used in this publication: Y. LuPower Electronics Research Centre, Department of Electrical EngineeringRefereed conference paper2001-2002 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Chick tendon fibroblast transcriptome and shape depend on whether the cell has made its own collagen matrix

Collagen- and fibrin-based gels are extensively used to study cell behaviour. However, 2D-3D and collagen-fibrin comparisons of gene expression, cell shape and mechanotransduction, with an in vivo reference, have not been reported. Here we compared chick tendon fibroblasts (CTFs) at three stages of embryonic development with CTFs cultured in collagen- or fibrin-based tissue engineered constructs (TECs). CTFs synthesised their own collagen matrix in fibrin-based TECs and better recapitulated the gene expression, collagen fibril alignment and cell shape seen in vivo. In contrast, cells in 3D collagen gels exhibited a 2D-like morphology and expressed fewer of the genes expressed in vivo. Analysis of YAP/TAZ target genes showed that collagen gels desensitise mechanotransduction pathways. In conclusion, gene expression and cell shape are similar on plastic and 3D collagen whereas cells in 3D fibrin have a shape and transcriptome better resembling the in vivo situation. Implications for wound healing are discussed

Scalp acupuncture for acute ischemic stroke: a meta-analysis of randomized controlled trials

Scalp acupuncture (SA) is a commonly used therapeutic approach for stroke throughout China and elsewhere in the world. The objective of this study was to assess clinical efficacy and safety of SA for acute ischemic stroke. A systematical literature search of 6 databases was conducted to identify randomized controlled trials (RCTs) of SA for acute ischemic stroke compared with western conventional medicines (WCMs). All statistical analyses were performed by the Rev Man Version 5.0. Eight studies with 538 participants were included in the studies. The studies were deemed to have an unclear risk of bias based on the Cochrane Back Review Group. Compared with the WCM, 6 RCTs showed significant effects of SA for improving neurological deficit scores (P < 0.01); 4 RCTs showed significant effects of SA for favoring the clinical effective rate (P < 0.01) However, the adverse events have not been documented. In conclusion, SA appears to be able to improve neurological deficit score and the clinical effective rate when compared with WCM, though the beneficial effect from SA is possibly overvalued because of generally low methodology of the included trials. No evidence is available for adverse effects. Rigorous well-designed clinical trials are needed.published_or_final_versio

Improved corrosion resistance of plasma carbon coated NiTi orthopedic materials

Nickel titanium (NiTi) alloys are useful in orthopedic applications because of their super-elastic properties and shape memory effects. However, when NiTi is used for a prolonged period of time, harmful Ni ions can leach out into the surrounding body fluid inside a human body, and so it is important to design a method to impede the out-diffusion of nickel from the materials into the biological medium. We aim at producing a barrier to mitigate the release of Ni ions during normal use. Carbon coatings have been shown to possess excellent bio-compatibility and good mechanical strength. In this work, amorphous hydrogenated DLC films with a graded C/NiTi interface were fabricated by plasma immersion ion implantation & deposition (PU & D) to provide such a barrier layer on NiTi. The elemental depth profiles and film thickness were determined by X-ray photoelectron spectroscopy (XPS) whereas the surface morphology was evaluated using atomic force microscopy (AFM). The film structure was studied by X-ray diffraction (XRD) and Raman spectroscopy. The corrosion resistance of the film was investigated using electrochemical tests based on ASTM G5-94. Compared to the control sample, the corrosion potential of the sample with the carbon coating changes from -250 to -50 mV and the film breakdown potential increases from 250 to 1200 mV. The corrosion current also diminishes from 10-6 to 10-7 A. The simulated body fluid (SBF) solutions after the electrochemical test were analyzed for Ni concentrations by inductively-coupled plasma mass spectrometry (ICPMS) and that data show that a much smaller amount of Ni has been released from the treated sample surface compared to the untreated control sample surface. Our results thus indicate that the deposited DLC film is effective in retarding the release of Ni ions from the bulk materials and more superior corrosion resistance is achieved based on our tests in a simulated fluid medium and at human body temperature.published_or_final_versio

Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy

Purpose: Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence. Methods and Results: Using patient-derived xenograft (PDX) mouse models of CD19+ B cell acute lymphoblastic leukemia (B-ALL), we show that priming leukemia-bearing mice with 5-azacytidine (AZA) enhances CAR T cell therapy. AZA given 1 day prior to CAR T cell infusion delayed leukemia growth and promoted CAR T cell expansion and effector function. Priming leukemia cells with AZA increased CAR T cell/target cell conjugation and target cell killing, promoted CAR T cell divisions and expanded IFNγ+ effector T cells in co-cultures with CD19+ leukemia Nalm-6 and Raji cells. Transcriptome analysis revealed activation of diverse immune pathways in leukemia cells isolated from mice treated with AZA. We propose that epigenetic priming with AZA induces transcriptional changes that sensitize tumor cells to subsequent CAR T cell treatment. Among the candidate genes up-regulated by AZA is TNFSF4 which encodes OX40L, one of the strongest T cell co-stimulatory ligands. OX40L binds OX40, the TNF receptor superfamily member highly specific for activated T cells. TNFSF4 is heterogeneously expressed in a panel of pediatric PDXs, and high TNFSF4 expression correlated with increased CAR T cell numbers identified in co-cultures with individual PDXs. High OX40L expression in Nalm-6 cells increased their susceptibility to CAR T cell killing while OX40L blockade reduced leukemia cell killing. Conclusion: We propose that treatment with AZA activates OX40L/OX40 co-stimulatory signaling in CAR T cells. Our data suggest that the clinical use of AZA before CAR T cells could be considered