Implantable Sensor System for Remote Detection of a Restenosis Condition

Part 7: Perceptional SystemsInternational audienceThe increase of life expectancy in the European Union, and the high risk of cardiovascular diseases associated with age, are some of the main factors to contribute to the rise of healthcare costs. An intelligent stent (e-stent), capable of obtaining and transmitting real-time measurements of physiological parameters for its clinical consultation, can be a useful tool for long-term monitoring, diagnostic, and early warning system for arterial blockage without patient hospitalization. In this paper, a behavioural model of capacitive Micro-Electro-Mechanical (MEMS) pressure sensor is proposed and simulated under several restenosis conditions. Special attention has been given to the need of an accurate fault model, obtained from realistic finite-element simulations,to ensure long-term reliability; particularly for those faults whose behavior cannot be easily described by an analytical model

Bendamustine: Safety and Efficacy in the Management of Indolent Non-Hodgkins Lymphoma

Bendamustine (Treanda, Ribomustin) was recently approved by the US Food and Drug Administration (FDA) for treatment of patients with rituximab refractory indolent lymphoma and is expected to turn into a frontline therapy option for indolent lymphoma. This compound with amphoteric properties was designed in the former Germany Democratic Republic in 1960s and re-discovered in 1990s with multiple successive well-designed studies. Bendamustine possesses a unique mechanism of action with potential antimetabolite properties, and only partial cross-resistance with other alkylators. Used in combination with rituximab in vitro, bendamustine shows synergistic effects against various leukemia and lymphoma cell lines. In clinical studies, bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median progression-free survival of 23–24 months. The optimal dosing and schedule of bendamustine administration is largely undecided and varies among studies. Results of ongoing trials and dose-finding studies will help to further help ascertain the optimal place of bendamustine in the management of indolent NHL

A Damage Mechanics Approach to Fatigue Assessment in Offshore Structures

This article is intended to describe the development of a fatigue damage model capable of assessing fatigue damage in offshore structures. This is achieved by for mulating a set of damage coupled constitutive and evolution equations which make the for mulation of a unified approach possible under both low and high cycle fatigue damage and consistent with the structural dynamic response of the changing/deteriorating material be haviors. The structural analysis for the whole designed period, say about 30 years, can be carried out with the aid of the proposed analytical procedure, in which the fundamental characteristics of sea wave statistics responsible for the structural dynamic response can be sufficiently considered. An offshore structure subject to complex ocean environment is described by a general stochastic system which embeds a group of stochastic subsystems, each characterizing a duty cycle. An effective analytical method is established by introduc ing the concept of duty strain range with a clear mathematical definition and its analytical solution which covers all possible spectral parameters. The history-dependent damage is also included in the damage model so that the overload effects can be analyzed. It should be pointed out that the whole procedure can be fully computerized such that the practical or engineering significance of varying design variables can be readily highlighted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67255/2/10.1177_105678959300200405.pd

An analysis of growth, differentiation and apoptosis genes with risk of renal cancer

We conducted a case-control study of renal cancer (987 cases and 1298 controls) in Central and Eastern Europe and analyzed genomic DNA for 319 tagging single-nucleotide polymorphisms (SNPs) in 21 genes involved in cellular growth, differentiation and apoptosis using an Illumina Oligo Pool All (OPA). A haplotype-based method (sliding window analysis of consecutive SNPs) was used to identify chromosome regions of interest that remained significant at a false discovery rate of 10%. Subsequently, risk estimates were generated for regions with a high level of signal and individual SNPs by unconditional logistic regression adjusting for age, gender and study center. Three regions containing genes associated with renal cancer were identified: caspase 1/5/4/ 12(CASP 1/5/4/12), epidermal growth factor receptor (EGFR), and insulin-like growth factor binding protein-3 (IGFBP3). We observed that individuals with CASP1/5/4/12 haplotype (spanning area upstream of CASP1 through exon 2 of CASP5) GGGCTCAGT were at higher risk of renal cancer compared to individuals with the most common haplotype (OR:1.40, 95% CI:1.10-1.78, p-value = 0.007). Analysis of EGFR revealed three strong signals within intron 1, particularly a region centered around rs759158 with a global p = 0.006 (GGG: OR:1.26, 95% CI:1.04-1.53 and ATG: OR:1.55, 95% CI:1.14-2.11). A region in IGFBP3 was also associated with increased risk (global p = 0.04). In addition, the number of statistically significant (p-value 0.05) SNP associations observed within these three genes was higher than would be expected by chance on a gene level. To our knowledge, this is the first study to evaluate these genes in relation to renal cancer and there is need to replicate and extend our findings. The specific regions associated with risk may have particular relevance for gene function and/or carcinogenesis. In conclusion, our evaluation has identified common genetic variants in CASP1, CASP5, EGFR, and IGFBP3 that could be associated with renal cancer risk

LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast cancer

Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We show here that LARG, from 11q23, has functional characteristics of a tumor suppressor. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, utilizing both loss of heterozygosity (LOH) analysis and microarray comparative genomic hybridization (CGH). LARG (also called ARHGEF12), identified from the analyzed region, was underexpressed in 34% of primary breast carcinomas and 80% of breast cancer cell lines including the MCF-7 line. Multiplex ligation-dependent probe amplification on 30 primary breast cancers and six breast cancer cell lines showed that LARG had the highest frequency of deletion compared to the BCSC-1 and TSLC1 genes, two known candidate tumor suppressor genes from 11q. In vitro analysis of breast cancer cell lines that underexpress LARG showed that LARG could be reactivated by trichostatin A, a histone deacetylase inhibitor, but not by 5-Aza-2{prime}-deoxycytidine, a demethylating agent. Bisulfite sequencing and quantitative high-throughput analysis of DNA methylation confirmed the lack of CpG island methylation in LARG in breast cancer. Restoration of LARG expression in MCF-7 cells by stable transfection resulted in reduced proliferation and colony formation, suggesting that LARG has functional characteristics of a tumor suppressor gene

Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors

OnlinePublAccurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.Nicole Dmochowska, Valentina Milanova, Ramesh Mukkamala, Kwok Keung Chow, Nguyen T. H. Pham, Madduri Srinivasarao, Lisa M. Ebert, Timothy Stait-Gardner, Hien Le, Anil Shetty, Melanie Nelson, Philip S. Low, and Benjamin Thierr

Synchronization of coupled limit cycles

A unified approach for analyzing synchronization in coupled systems of autonomous differential equations is presented in this work. Through a careful analysis of the variational equation of the coupled system we establish a sufficient condition for synchronization in terms of the geometric properties of the local limit cycles and the coupling operator. This result applies to a large class of differential equation models in physics and biology. The stability analysis is complemented with a discussion of numerical simulations of a compartmental model of a neuron.Comment: Journal of Nonlinear Science, accepte