The influence of operator position,height and body orientation on eye lens dose in interventional radiology and cardiology: Monte Carlo simulations versus realistic clinical measurements

ObjectiveThis paper aims to provide some practical recommendations to reduce eye lens dose for workers exposed to X-rays in interventional cardiology and radiology and also to propose an eye lens correction factor when lead glasses are used.MethodsMonte Carlo simulations are used to study the variation of eye lens exposure with operator position, height and body orientation with respect to the patient and the X-ray tube. The paper also looks into the efficiency of wraparound lead glasses using simulations. Computation results are compared with experimental measurements performed in Spanish hospitals using eye lens dosemeters as well as with data from available literature.ResultsSimulations showed that left eye exposure is generally higher than the right eye, when the operator stands on the right side of the patient. Operator height can induce a strong dose decrease by up to a factor of 2 for the left eye for 10-cm-taller operators. Body rotation of the operator away from the tube by 45°–60° reduces eye exposure by a factor of 2. The calculation-based correction factor of 0.3 for wraparound type lead glasses was found to agree reasonably well with experimental data.ConclusionsSimple precautions, such as the positioning of the image screen away from the X-ray source, lead to a significant reduction of the eye lens dose. Measurements and simulations performed in this work also show that a general eye lens correction factor of 0.5 can be used when lead glasses are worn regardless of operator position, height and body orientation.     

Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids, leaving residues in the environment. There is now evidence that low doses of insecticides can have positive effects on pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction, and olfactory synaptic transmission is cholinergic, neonicotinoid residues could modify chemical communication. We recently showed that treatments with different sublethal doses of clothianidin could either enhance or decrease behavioural sex pheromone responses in the male moth, Agrotis ipsilon. We investigated now effects of the behaviourally active clothianidin doses on the sensitivity of the peripheral and central olfactory system. We show with extracellular recordings that both tested clothianidin doses do not influence pheromone responses in olfactory receptor neurons. Similarly, in vivo optical imaging does not reveal any changes in glomerular response intensities to the sex pheromone after clothianidin treatments. The sensitivity of intracellularly recorded antennal lobe output neurons, however, is upregulated by a lethal dose 20 times and downregulated by a dose 10 times lower than the lethal dose 0. This correlates with the changes of behavioural responses after clothianidin treatment and suggests the antennal lobe as neural substrate involved in clothianidin-induced behavioural changes.     

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study

PurposeTo evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR).MethodsThree anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom.ResultsThe use of AEC produced a significant dose reduction (p < 0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p < 0.01) and reduced SNR and CNR (p < 0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency.ConclusionsIn chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices.     

Influence of CYP3A4, CYP3A5 and MDR-1 polymorphisms on tacrolimus pharmacokinetics and early renal dysfunction in liver transplant recipients

Objectives

Tacrolimus is a widely used immunosuppressive drug in organ transplantation. The oral bioavailability of tacrolimus varies greatly between individuals and depends largely on the activity of both the cytochrome P450 3A (CYP3A) subfamily and P-glycoprotein (P-gp). The possible influence of single nucleotide polymorphisms (SNPs) of CYP3A subfamily and P-gp (MDR-1) in liver transplant recipients has recently been indicated as one of the most important variables affecting the pharmacokinetics of tacrolimus and the renal injury induced by tacrolimus.

Methods

A total of 216 liver transplant recipients were enrolled in this study. The recipients' mean follow-up time was 52 mo (range from 16 to 96 mo). All liver transplant recipients were all in a stable stage with normal serum creatinine (SCr). All liver transplant recipients treated with tacrolimus were genotyped for CYP3A5 (6986A>G), CYP3A4 intron 6 (CYP3A4*22), MDR-1 exon 26 (3435C>T) and exon 12 (1236 C>T) SNPs by HRM analysis (high-resolution melting curve analysis). Recipients were defined as the early renal injury by the elevation of different microproteins in the urine including microalbumin (MA), urine immunoglobulin G (IGU), urine transferrin (TRU) and α1-microglobulin (A1M).

Results

The daily dose of tacrolimus was higher for recipients with CYP3A5*1/*1 (AA) genotype than those with CYP3A5*3/*3 (GG) genotype [3.0 (2.0–4.0) versus 2.0 (1.5–2.5) mg/d, P < 0.05]. The concentration/dose ratio of recipients with CYP3A5*1 homozygotes was lowest compared to recipients with CYP3A5*3/*3 and CYP3A5*1/*3 genotypes. Furthermore, the recipients carrying CYP3A5*3 allele were associated with increased risk of early renal glomerular injury compared to the recipients carrying CYP3A5*1 allele (P = 0.01). MDR-1 polymorphisms were not related with tacrolimus pharmacokinetics and early renal injury.

Conclusion

CYP3A5 6986A>G genetic polymorphism affected daily dose requirements, concentration and nephrotoxicity of tacrolimus. Screening for this single nucleotide polymorphism before the transplantation might be helpful for the selection of adequate initial daily dose and to achieve the desired immunosuppression outcome.     

Dose finding for continuous and ordinal outcomes with a monotone objective function: a unified approach

Summary .  In many phase I trials, the design goal is to find the dose associated with a certain target toxicity rate. In some trials, the goal can be to find the dose with a certain weighted sum of rates of various toxicity grades. For others, the goal is to find the dose with a certain mean value of a continuous response. In this article, we describe a dose-finding design that can be used in any of the dose-finding trials described above, trials where the target dose is defined as the dose at which a certain monotone function of the dose is a prespecified value. At each step of the proposed design, the normalized difference between the current dose and the target is computed. If that difference is close to zero, the dose is repeated. Otherwise, the dose is increased or decreased, depending on the sign of the difference.     

No influence of 20 and 400 microT, 50 Hz magnetic field exposure on cognitive function in humans

The aim of the present study was to investigate cognitive effects of a continuous, vertical extremely low frequency (ELF) magnetic field (MF) of 20 and 400 microT 50 Hz in healthy young men during performance on cognitive tests. Thirty-two volunteers (20-30 years old, mean 22.6 +/- 2.2 years) participated in this double blind study. The test protocol consisted of a set of tests: divided attention, flexibility, memory updating, digit span, digit span with articulary suppression, and time perception. The total duration of the exposure was 65 min. Participants were assigned four sessions: three conditions in the helmet (sham exposure, 20 and 400 microT) and one condition out of the helmet (to control the expectancy effect). No effect of MF exposure was observed on performance.     

Relationship between Cancer Slope Factor and Acute Toxicity in Rats and Fish

The purpose of this study was to examine bivariate relationships among cancer slope factor (CSF) and acute toxicity in rats and salmonid fish. Chemicals (n=43) were selected based on the availability of both oral CSF and acute toxicity data (rat oral median lethal dose [LD50] or salmonid median lethal concentration [LC50]). Rat oral LD50, salmonid LC50, and oral CSF data were log-transformed, and a Bonferroni-adjusted alpha level was set at 0.05 for subsequent correlation analysis. A significant correlation was observed between CSF and rat oral LD50 (r=?0.61) but not for CSF and salmonid LC50 (r=?0.29). Moreover, rat and fish acute toxicity were not significantly correlated (r=0.38). The significant correlation between CSF and rat oral LD50 compares favorably with published results reported in related studies. Accordingly, these results support prediction of carcinogenic potency, expressed as oral CSF, based in part on acute toxicity in rats.     

DLPC and SAMe prevent alpha1(I) collagen mRNA up-regulation in human hepatic stellate cells, whether caused by leptin or menadione

We previously reported that the combination of dilinoleoylphosphatidylcholine (DLPC) and S-adenosylmethionine (SAMe), which have antioxidant properties and antifibrogenic actions, prevented leptin-stimulated tissue inhibitor of metalloproteinase (TIMP)-1 production in hepatic stellate cells (HSCs) by inhibiting H2O2-mediated signal transduction. We now show that DLPC and SAMe inhibit alpha1(I) collagen mRNA expression induced by leptin or menadione in LX-2 human HSCs. We found that DLPC and SAMe prevent H2O2 generation and restore reduced glutathione (GSH) depletion whether caused by leptin or menadione. Blocking H2O2 signaling through ERK1/2 and p38 pathways resulted in a complete inhibition of leptin or menadione-induced alpha1(I) collagen mRNA. The inhibition of collagen mRNA by DLPC and SAMe combined is at least two times more effective than that by DLPC or SAMe alone. In conjunction with the prevention of TIMP-1 production, the ability of DLPC and SAMe to inhibit alpha1(I) collagen mRNA expression provides a mechanistic basis for these innocuous compounds in the prevention of hepatic fibrosis, because enhanced TIMP-1 and collagen productions are associated with hepatic fibrogenesis and their attenuation may diminish fibrosis.     

Total Hourglass Control - A Robust Finite Element Formulation for the Calculation of Organ Deformations

For use in a virtual reality based laparoscopic surgery simulator methods have been developed to model the mechanical behavior of soft tissue. Explicit Finite Element analysis turned out to be a robust basis when the approximation of hyperelastic materials is used. To reduce calculation times reduced volume integration schemes were applied, where classical hourglass control leads to drastic errors which make a simulation expanding over a long period of time impossible. Therefore, the total hourglass control scheme was developed and is presented here for several material laws. This new formulation takes the existence of the elastic potential of a hyperelastic material into account and leads to robust simulations without loss of accuracy. This is demonstrated with the off-line simulation of a model of an uterus and its adnexe.