Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults.

Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US$570,404. Costs were significantly higher for bleeding/elevated international normalized ratio (US$9906 vs. US$2251, p = 6.58 × 10-3) compared to other ADRs, and for drugs acting on the blood coagulation system (US$9884 vs. US$2229, p = 4.41 × 10-3) compared to other drug classes. There were higher incremental laboratory costs due to ADRs causing or being present at admission. The estimated breakeven cost of a pre-emptive PGx test for patients taking warfarin, clopidogrel, chemotherapeutic and neuropsychiatric drugs was US$114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions

Transcriptional profiling of ErbB signalling in mammary luminal epithelial cells - interplay of ErbB and IGF1 signalling through IGFBP3 regulation

Background: Members of the ErbB family of growth factor receptors are intricately linked with epithelial cell biology, development and tumourigenesis; however, the mechanisms involved in their downstream signalling are poorly understood. Indeed, it is unclear how signal specificity is achieved and the relative contribution each receptor has to specific gene expression.Methods: Gene expression profiling of a human mammary luminal epithelial cell model of ErbB2-overexpression was carried out using cDNA microarrays with a common RNA reference approach to examine long-term overlapping and differential responses to EGF and heregulin beta1 treatment in the context of ErbB2 overexpression. Altered gene expression was validated using quantitative real time PCR and/or immunoblotting. One gene of interest was targeted for further characterisation, where the effects of siRNA-mediated silencing on IGF1-dependent signalling and cellular phenotype were examined and compared to the effects of loss of ErbB2 expression.Results: 775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e. g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were enhanced in ErbB2-overexpressing cells, whilst loss of ErbB2 expression by siRNA silencing reduced IGF1 signalling. Furthermore, IGFBP3 knockdown resulted in basal ERK and Akt activation in luminal epithelial cells and increased invasiveness and anchorage-independent colony formation in SKBR3 cells.Conclusions: These data show IGFBP3 as a negative regulator of transformation and that its down-regulation enhances IGF1-dependent signalling. They also show that ErbB2 can up-regulate IGF1-dependent signalling, possibly via the regulated expression of IGFBP3

Towards the AlexNet Moment for Homomorphic Encryption: HCNN, theFirst Homomorphic CNN on Encrypted Data with GPUs

Deep Learning as a Service (DLaaS) stands as a promising solution for cloud-based inference applications. In this setting, the cloud has a pre-learned model whereas the user has samples on which she wants to run the model. The biggest concern with DLaaS is user privacy if the input samples are sensitive data. We provide here an efficient privacy-preserving system by employing high-end technologies such as Fully Homomorphic Encryption (FHE), Convolutional Neural Networks (CNNs) and Graphics Processing Units (GPUs). FHE, with its widely-known feature of computing on encrypted data, empowers a wide range of privacy-concerned applications. This comes at high cost as it requires enormous computing power. In this paper, we show how to accelerate the performance of running CNNs on encrypted data with GPUs. We evaluated two CNNs to classify homomorphically the MNIST and CIFAR-10 datasets. Our solution achieved a sufficient security level (> 80 bit) and reasonable classification accuracy (99%) and (77.55%) for MNIST and CIFAR-10, respectively. In terms of latency, we could classify an image in 5.16 seconds and 304.43 seconds for MNIST and CIFAR-10, respectively. Our system can also classify a batch of images (> 8,000) without extra overhead

Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells

Rhein is a natural product purified from herbal plants such as Rheum palmatum, which has been shown to have anti-angiogenesis and anti-tumor metastasis properties. However, the biological effects of rhein on the behavior of breast cancers are not completely elucidated. To evaluate whether rhein might be useful in the treatment of breast cancer and its cytotoxic mechanism, we analyzed the impact of rhein treatment on differential protein expression as well as redox regulation in a non-invasive breast cancer cell line, MCF-7, and an invasive breast cancer cell line, MDA-MB-231, using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry. This proteomic study revealed that 73 proteins were significantly changed in protein expression; while 9 proteins were significantly altered in thiol reactivity in both MCF-7 and MDA-MB-231 cells. The results also demonstrated that rhein-induced cytotoxicity in breast cancer cells mostly involves dysregulation of cytoskeleton regulation, protein folding, the glycolysis pathway and transcription control. A further study also indicated that rhein promotes misfolding of cellular proteins as well as unbalancing of the cellular redox status leading to ER-stress. Our work shows that the current proteomic strategy offers a high-through-put platform to study the molecular mechanisms of rhein-induced cytotoxicity in breast cancer cells. The identified differentially expressed proteins might be further evaluated as potential targets in breast cancer therapy

Technology Anxiety and Implicit Learning Ability Affect Technology Leadership to Promote the use of Information Technology at Elementary Schools

Abstract“Oversold & underused” is a criticism by Cuban (2001) of the investment of information technology (IT) in the classroom. Recently, Taiwan's educational administration has provided considerable financial support to IT in elementary schools, but few reports have provided evidence of its successful use. The present study aims to identify the personal factors that affect principals’ beliefs about the promotion of IT in their schools. 331 data were collected and analyzed with AMOS 19.0. The results of this study indicated that greater technology anxiety was negatively associated with perceived ease of using (PEU) IT, whereas implicit learning ability was positively correlated with perceived usefulness of IT. Technology leadership increased significantly with PEU and perceived usefulness (PU), it is also associated with the intention to overcome difficulties in promoting information technology in schools. The implications of this study may contribute to the reduction of principals’ technology anxiety, increasing their implicit learning ability and therefore fostering the future implementation of IT in schools, changing the myth of technology as “oversold & underused”