Cost-effectiveness of osimertinib versus standard EGFR-TKI as first-line treatment for locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia.

Objectives: To assess the cost-effectiveness of osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib, as first-line treatment for patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia from a healthcare system perspective. Methods: A partitioned survival model comprising three mutually exclusive health states with a five-year time horizon was developed. Model inputs were sourced from the pivotal trial (FLAURA) and published literature. Incremental cost-effectiveness ratios (ICERs), in terms of cost per quality-adjusted life-year (QALY) gained and cost per life-year (LY) gained, were calculated. Uncertainty of the results was assessed using deterministic and probabilistic sensitivity analyses. Results: Compared with standard EGFR-TKIs, osimertinib was associated with a higher incremental cost of A$118,502, and an incremental benefit of 0.274 QALYs and 0.313 LYs. The ICER was estimated to be A$432,197/QALY gained and A$378,157/LY gained. The base-case ICER was most sensitive to changes in cost of first-line osimertinib, time horizon, and choice of overall survival data (interim versus final analysis). Conclusions: At a willingness-to-pay threshold of A$50,000/QALY, first-line osimertinib is not cost-effective compared with standard EGFR-TKIs in Australia based on the current published price. To achieve acceptable cost-effectiveness, the cost of first-line osimertinib needs to be reduced by at least 68.4%

Probing the gateway to superheavy nuclei in cranked relativistic Hartree-Bogoliubov theory

The cranked relativistic Hartree+Bogoliubov theory has been applied for a systematic study of the nuclei around 254No, the heaviest nuclei for which detailed spectroscopic data are available. The deformation, rotational response, pairing correlations, quasi-particle and other properties of these nuclei have been studied with different relativistic mean field (RMF) parametrizations. For the first time, the quasi-particle spectra of odd deformed nuclei have been calculated in a fully self-consistent way within the framework of the RMF theory. The energies of the spherical subshells, from which active deformed states of these nuclei emerge, are described with an accuracy better than 0.5 MeV for most of the subshells with the NL1 and NL3 parametrizations. However, for a few subshells the discrepancy reach 0.7-1.0 MeV. The implications of these results for the study of superheavy nuclei are discussed.Comment: 7 pages, 3 figures, Proceedings of the Conference on Frontiers of Nuclear Structure, Berkeley, California, July 29th - August 2nd, 2002, UC Berkeley, Clark Kerr Campus, in pres

DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

A Storm in a "T" Cup

We revisit the process of transversification and agglomeration of particle momenta that are often performed in analyses at hadron colliders, and show that many of the existing mass-measurement variables proposed for hadron colliders are far more closely related to each other than is widely appreciated, and indeed can all be viewed as a common mass bound specialized for a variety of purposes.Comment: 3 pages, 2 figures, presented by K.C. Kong at the 19th Particles and Nuclei International Conference, PANIC 2011, MIT, Cambridge, MA (July 24-29, 2011

Characterisation of Bidor Kaolinite and Illite

Two types of commercial clay minerals from the Bidor region of Perak were studied. From the X-ray diffraction study, these clays were identified as disordered kaolinite and 2 M polymorph of illite. The morphologies, the surface properties, the pore structures and the infrared absorption properties were examined. The basis for the identification of these clays is discussed

TUNNELING FROM SUPER- TO NORMAL- DEFORMED MINIMA IN NUCLEI

An excited minimum, or false vacuum, gives rise to a highly elongated superdeformed (SD) nucleus. A brief review of superdeformation is given, with emphasis on the tunneling from the false to the true vacuum, which occurs in the feeding and decay of SD bands. During the feeding process the tunneling is between hot states, while in the decay it is from a cold to a hot state. The {gamma} spectra connecting SD and normal-deformed (ND) states provide information on several physics issues: the decay mechanism; the spin/parity quantum numbers, energies and microscopic structures of SD bands; the origin of identical SD bands; the quenching of pairing with excitation energy; and the chaoticity of excited ND states at 2.5-5 MeV. Other examples of tunneling in nuclei, which are briefly described, include the possible role of tunneling in {Delta}I = 4 bifurcation in SD bands, sub-barrier fusion and proton emitters