We established the IMMEnSE (International Multiple Myeloma rESEarch) consortium, to increase our understanding of the genetic determinants of multiple myeloma (MM) risk, response to therapy and survival. At present we have DNA samples of over 3200 MM cases and 3000 healthy controls from 10 countries, mainly in Europe. For the majority of the cases clinical data on known prognostic factors, therapy outcome and survival have been also collected. We already performed several association studies in the context of the IMMEnSE consortium. In particular, associations were found between MM risk and SNPs in the ABCB1 gene, which encodes for an efflux pump that has a key role in protecting cells from chemical damage (rs10264990: odds ratio (OR) =0.79, 95% confidence interval (CI) 0.68-0.91; p=0.001, and rs17327442: OR=1.99; 95%CI 1.32-3.02; p=0.001). We also investigated the 8q24 region, which has been shown to harbor multiple loci of susceptibility to various cancers, and found an association between a SNP mapping in this region and MM risk (rs2456449: OR=1.37; 95%CI 1.12-1.68; p=0.0022). In addition, IMMEnSE cases and controls were also genotyped for three MM risk SNPs from the first genome-wide association study (GWAS), and the association of two of them (rs4487645 on chromosome 7p15.3 and rs6746082 on chromosome 2p23.3) was confirmed. Finally, SNPs of key telomere-related genes were genotyped and telomere length was measured in MM cases and controls, and a pleiotropic and functional variant of the TERT gene was found to be associated with reduced MM risk (rs2242652: OR=0.81; 95%CI 0.72-0.92; p=0.001). A suggestive association between longer telomeres and increased MM risk was also found (ptrend=0.01). We will study new SNPs emerging as promising candidates from ongoing GWAS on MM risk and survival, as well as SNPs of key genes involved in the pathogenesis of MM. Finally, we plan to study methylation status of key genes involved in MM etiology, and mitochondrial copy number. The role of all these factors will be investigated in relation to MM risk and prognosis. Collection of samples and data of MM cases and controls is ongoing, as well as of subjects with monoclonal gammopathy of undetermined significance (MGUS). Disclosures No relevant conflicts of interest to declare.


ABSTRACT Purpose: The aim of the study was to develop and evaluate matrix based controlled drug delivery system by direct compression technique of Bupropion hydrochloride tablet and stability studies. Methods: Controlled release tablets were prepared by employing Eudragit RS 100, HPMC K15M, HPMC K100M at different concentration. Result and conclusion: All 10 batches pass friability, hardness, weight variation, assay but only three batches (CRB3D, CRB4D and CRB7D) passed the dissolution as per USP 30 NF25 for extended release tablet of Bupropion hydrochloride. All batches follow Higuchi Model followed by Pappes model. HPMC (K15M & K100M) as a matrix polymer used in tablet formulation provide a good initial retardation in the release as well as helped to enhance the overall release rate of the drug than that of Eudagit RS 100. It was observed that increase in polymer concentration retards the release of drugs in case of HPMC K15 M and HPMC K100 M. Self life of CRB7D tablet was found to be 2.37year.


Several theoretical equations are derived which determine the vacuum permittivity, vacuum permeability, free impedance and speed of light to a highly convergent value on the order of 10 − 8 to 10 − 9 . Their dependence is related to the particle horizon, Hubble horizon, Planck length, proton wavelength and the fine structure constant. Due to these highly convergent equations, an image of both the photon and the vacuum may start to emerge.