Application of the Johnson-Cook plasticity model in the finite element simulations of the nanoindentation of the cortical bone.

The mechanical behavior of the cortical bone in nanoindentation is a complicated mechanical problem. The finite element analysis has commonly been assumed to be the most appropriate approach to this issue. One significant problem in nanoindentation modeling of the elastic-plastic materials is pile-up deformation, which is not observed in cortical bone nanoindentation testing. This phenomenon depends on the work-hardening of materials; it doesn't occur for work-hardening materials, which suggests that the cortical bone could be considered as a work-hardening material. Furthermore, in a recent study [59], a plastic hardening until failure was observed on the micro-scale of a dry ovine osteonal bone samples subjected to micropillar compression. The purpose of the current study was to apply an isotropic hardening model in the finite element simulations of the nanoindentation of the cortical bone to predict its mechanical behavior. The Johnson-Cook (JC) model was chosen as the constitutive model. The finite element modeling in combination with numerical optimization was used to identify the unknown material constants and then the finite element solutions were compared to the experimental results. A good agreement of the numerical curves with the target loading curves was found and no pile-up was predicted. A Design Of Experiments (DOE) approach was performed to evaluate the linear effects of the material constants on the mechanical response of the material. The strain hardening modulus and the strain hardening exponent were the most influential parameters. While a positive effect was noticed with the Young's modulus, the initial yield stress and the strain hardening modulus, an opposite effect was found with the Poisson's ratio and the strain hardening exponent. Finally, the JC model showed a good capability to describe the elastoplastic behavior of the cortical bone.

Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas.

Genetic and epigenetic (DNA methylation, histone modifications, microRNA expression) crosstalk promotes inactivation of tumor suppressor genes or activation of oncogenes by gene loss/hypermethylation or duplications/hypomethylation, respectively. The 8p11-p12 chromosomal region is a hotspot for genomic aberrations (chromosomal rearrangements, amplifications and deletions) in several cancer forms, including breast carcinoma where amplification has been associated with increased proliferation rates and reduced patient survival. Here, an integrative genomics screen (DNA copy number, transcriptional and DNA methylation profiling) performed in 229 primary invasive breast carcinomas identified substantial coamplification of the 8p11-p12 genomic region and the MYC oncogene (8q24.21), as well as aberrant methylation and transcriptional patterns for several genes spanning the 8q12.1-q24.22 genomic region (ENPP2, FABP5, IMPAD1, NDRG1, PLEKHF2, RRM2B, SQLE, TAF2, TATDN1, TRPS1, VPS13B). Taken together, our findings suggest that MYC activity and aberrant DNA methylation may also have a pivotal role in the aggressive tumor phenotype frequently observed in breast carcinomas harboring 8p11-p12 regional amplification.

[Drug circuit in Lebanese hospitals]. / Le circuit du médicament dans les hôpitaux libanais.

BACKGROUND: Drug errors constitute a public health problem. The objective of our study was to describe drug circuit essential steps in the Lebanese hospitals, starting at prescription to administration, in comparison with Lebanese accreditation standards. We also evaluated technical drug errors. METHODS: A cross sectional study of all hospitals in Beirut and Mount Lebanon was carried out, where a pharmacist and a nurse per hospital answered anonymous standardized questionnaires. RESULTS: We found the drug circuit suffered from gaps in all 59 hospitals that were visited: doctors should increase efforts to clarify prescriptions and furnish necessary information for nurses, pharmacists better apply accreditation standards, and nurses verify and re-verify treatments before administration. CONCLUSION: Regulatory laws are necessary for all involved actors for best responding to the responsibility in question, that is patient security.

Comparative sensitivity of three populations of the cladoceran Moinodaphnia macleayi to acute and chronic uranium exposure.

Assessment of differences in the response of three different populations of the tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The populations tested included a laboratory stock (maintained for 10 years), a wild population collected from Bowerbird Billabong (an uncontaminated environment), and a population collected from Djalkmara Billabong (a relatively contaminated environment with elevated levels of uranium), located on the Ranger uranium mine site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was determined for all three populations. The no-observed-effect-concentration (NOEC; reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1, respectively, for all three populations. The 48 h EC50 (immobilization-lethality) for uranium ranged between 160-390 micrograms L-1 for all three populations. There was little difference in the response of the three populations of M. macleayi to acute and chronic uranium exposure, although the response of the laboratory population to chronic uranium exposure appeared more variable than the "wild" populations. There was no apparent tolerance in the population of M. macleayi obtained from Djalkmara Billabong when exposed to elevated levels of uranium. M. macleayi was significantly more sensitive to uranium exposure than other species previously tested. It was concluded that the sensitivity of the laboratory population (to uranium) is still representative of natural M. macleayi populations.

The acute and chronic toxicity of cadmium and zinc to two hydra species.

The potential of two hydra species, Hydra vulgaris (pink) and Hydra viridissima (green), for use as invertebrate models for toxicity testing of waterborne metals was investigated. The acute and subchronic toxicities of cadmium (a nonessential metal) and zinc (an essential metal) were determined. Results showed that both the hydra species were more sensitive to cadmium than to zinc, and that green hydra were more sensitive than pink hydra. The mean (SE) 96 h LC50 values of cadmium and zinc for pink hydra were 83 (8.5) and 2300 (150) micrograms/L, respectively. For green hydra, the respective 96 h LC50 values for cadmium and zinc were 3.0 (0.0) and 935 (46.5) micrograms/L. The respective 7-day no-observed-effect-concentrations (NOEC) and lowest-observed-effect-concentrations (LOEC) for pink hydra were < 13 and 13 micrograms/L for cadmium, and < 250 and 250 micrograms/L for zinc. The respective 7-day NOEC and LOEC values for green hydra were 0.4 and 0.8, microgram/L for cadmium, and 38 and 75 micrograms/L for zinc. Neither 1, 2, or 3 x 90-min pulse-exposures to 0.4, 0.8, or 1.5 micrograms/L of cadmium had any significant deleterious effect on total green hydra numbers after seven days in clean water. Green hydra appeared to be excellent freshwater invertebrate models for testing dissolved metals based on their sensitivity and the ability to rapidly assess population reproduction in the laboratory.