A new approach to deposit homogeneous samples of asbestos fibres for toxicological tests in vitro

In this paper we describe the results obtained with a novel method to prepare depositions of asbestos fibres for toxicological tests in vitro. The technique is based on a micro-dispenser, working as an inkjet printer, able to deposit micro-sized droplets from a suspension of fibres in a liquid medium; we used here a highly evaporating liquid (ethanol) to reduce the experimental time, however other solvents could be used. Both the amount and spatial distribution of fibres on the substrate can be controlled by adjusting the parameters of the micro-dispenser such as deposition area, deposition time, uniformity and volume of the deposited liquid. Statistical analysis of images obtained by optical and scanning electron microscopy shows that this technique produces an extremely homogeneous distribution of fibers. Specifically, the number of deposited single fibres is maximized (up to 20 times), a feature that is essential when performing viability tests where agglomerated or untangled fibrous particles need to be avoided

Strontium Substituted Tricalcium Phosphate Bone Cement: Short and Long‐Term Time‐Resolved Studies and In Vitro Properties

Due to a significant influence of strontium (Sr) on bone regeneration, Sr substituted beta-tricalcium phosphate (Sr-TCP) cement is prepared and investigated by short- and long-term time-resolved techniques. For short-term investigations, energy-dispersive X-ray diffraction, infrared spectroscopy, and, for the first time, terahertz time-domain spectroscopy techniques are applied. For long-term time-resolved studies, angular dispersive X-ray diffraction, scanning electron microscopy, mechanical tests, and behavior in Ringer solution are carried out. After 45 min of the cement setting, the Sr-TCP phase is no longer detectable. During this time period, an appearance and constant increase of the final brushite phase are registered. The compressive strength of the Sr-TCP cement increases from 4.5 MPa after 2 h of setting and reaches maximum at 13.3 MPa after 21 d. After cement soaking for 21 d in Ringer solution, apatite final product, with an admixture of brushite and TCP phases is detected. The cytotoxicity aspects of the prepared cement are investigated using NCTC 3T3 fibroblast cell line, and the cytocompatibility-by human dental pulp mesenchymal stem cells. The obtained results allow to conclude that the developed Sr-TCP cement is promising for biomedical applications for bone tissue

Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status ≤ 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m(2), every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m(2), every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable

A perspective on advanced signal generation techniques

The functionalities of signal sources have kept the pace with the mounting complexity of the available systems. It could appear, that the types of signal sources nowadays available on the market allow the user to satisfy every need in test and measurement applications. On the contrary, despite the wide range of functionalities provided by the very last generation sources, there is still room to imagine challenges and propose hypothetical architectures of generators suitable to face them. The speculative case of architectures made up of multiple direct digital synthesizers (DDS) circuits that operate synchronously to produce non periodic signals and emulate interesting scenarios is discussed

Spectral estimation of piece-constant waveforms generated by digital-to-analog converters

DACs are frequently utilized to generate non-standard waveforms. In particular any DACs approximate the desired waveform with a piece-constant one, produced by stepping up or down the output voltage of some amount at regular time intervals. The effect of the voltage steps characterizing piececonstant waveforms have been barely investigated in the past years. The paper presents a descriptive model for DACs that takes into account the piece-constant nature of the output waveform as well as non-idealities, such as time-base instability and non-linearity errors. The model describes well the behaviour of real DACs and permits to estimate the spectral features of the generated waveform, avoiding some pitfalls the simulation can be responsible for

ANOVA based approach for DAC diagnostics

In order to assess the performance of digital to analog converters (DAC) the attention is generally focused on the integral nonlinearity (INL). Useful diagnostic tools to detect the causes of poor linearity are the linearity and intermodulation errors, which can be evaluated from INL measurements. Linearity and intermodulation errors highlight and quantify erroneous calibration and unwanted interactions between current sources inside the DAC hardware. Unfortunately, their estimates, especially those related to high order intermodulation errors are characterized by high uncertainty. On the base of their very uncertain value it is difficult to establish if interactions represent relevant factors or not. It is shown that by means of the analysis of variance (ANOVA) the relevance of intermodulation errors can be assessed from a limited set counting a minimum of two INL measurements. ANOVA is in fact capable of distinguishing if the variance in INL measurements has to be addressed to active factors or noise, even if the effect of each factor is widespread upon different elements of the INL array and in different combinations with the other factors