Toxicity screenings of nanomaterials: challenges due to interference with assay processes and components of classic in vitro tests.

Given the multiplicity of nanoparticles (NPs), there is a requirement to develop screening strategies to evaluate their toxicity. Within the EU-funded FP7 NanoTEST project, a panel of medically relevant NPs has been used to develop alternative testing strategies of NPs used in medical diagnostics. As conventional toxicity tests cannot necessarily be directly applied to NPs in the same manner as for soluble chemicals and drugs, we determined the extent of interference of NPs with each assay process and components. In this study, we fully characterized the panel of NP suspensions used in this project (poly(lactic-co-glycolic acid)-polyethylene oxide [PLGA-PEO], TiO2, SiO2, and uncoated and oleic-acid coated Fe3O4) and showed that many NP characteristics (composition, size, coatings, and agglomeration) interfere with a range of in vitro cytotoxicity assays (WST-1, MTT, lactate dehydrogenase, neutral red, propidium iodide, (3)H-thymidine incorporation, and cell counting), pro-inflammatory response evaluation (ELISA for GM-CSF, IL-6, and IL-8), and oxidative stress detection (monoBromoBimane, dichlorofluorescein, and NO assays). Interferences were assay specific as well as NP specific. We propose how to integrate and avoid interference with testing systems as a first step of a screening strategy for biomedical NPs.

Data-division-specific robustness and power of randomization tests for ABAB designs

This study deals with the statistical properties of a randomization test applied to an ABAB design in cases where the desirable random assignment of the points of change in phase is not possible. In order to obtain information about each possible data division we carried out a conditional Monte Carlo simulation with 100,000 samples for each systematically chosen triplet. Robustness and power are studied under several experimental conditions: different autocorrelation levels and different effect sizes, as well as different phase lengths determined by the points of change. Type I error rates were distorted by the presence of autocorrelation for the majority of data divisions. Satisfactory Type II error rates were obtained only for large treatment effects. The relationship between the lengths of the four phases appeared to be an important factor for the robustness and the power of the randomization test.

Randomization tests for ABAB designs: Comparing-data-division-specific and common distributions

Monte Carlo simulations were used to generate data for ABAB designs of different lengths. The points of change in phase are randomly determined before gathering behaviour measurements, which allows the use of a randomization test as an analytic technique. Data simulation and analysis can be based either on data-division-specific or on common distributions. Following one method or another affects the results obtained after the randomization test has been applied. Therefore, the goal of the study was to examine these effects in more detail. The discrepancies in these approaches are obvious when data with zero treatment effect are considered and such approaches have implications for statistical power studies. Data-division-specific distributions provide more detailed information about the performance of the statistical technique.

Measuring individuals' response quality in self-administered psychological tests : an introduction to Gendre's functional method

The functional method is a new test theory using a new scoring method that assumes complexity in test structure, and thus takes into account every correlation between factors and items. The main specificity of the functional method is to model test scores by multiple regression instead of estimating them by using simplistic sums of points. In order to proceed, the functional method requires the creation of hyperspherical measurement space, in which item responses are expressed by their correlation with orthogonal factors. This method has three main qualities. First, measures are expressed in the absolute metric of correlations; therefore, items, scales and persons are expressed in the same measurement space using the same single metric. Second, factors are systematically orthogonal and without errors, which is optimal in order to predict other outcomes. Such predictions can be performed to estimate how one would answer to other tests, or even to model one's response strategy if it was perfectly coherent. Third, the functional method provides measures of individuals' response validity (i.e., control indices). Herein, we propose a standard procedure in order to identify whether test results are interpretable and to exclude invalid results caused by various response biases based on control indices.

Mittausjärjestelmän kehittäminen massansyöttöön

Tämän diplomityön tavoitteena on kehittää menetelmä mitata keskisakeuksisen sellumassan virtausta; suuntaa ja suuruutta, vapaassa tilassa ja kehittää koelaite, jolla sellupesurin massansyöttötapahtumaa voidaan tutkia sekä rakenteellisesta että prosessinäkökulmasta. Virtausmittausmenetelmän kehityksessä arvioitiin ensin erilaisten perusmittausmenetelmien soveltuvuutta keskisakeuksisen sellumassan virtausmittaukseen. Valitun menetelmän, vastusvenymäliuskamittauksen, kehityksessä ideoitiin sekä anturin mittoja ja geometriaa että virtauskappaleiden geometriaa. Lopullisella anturikonstruktiolla suoritettiin virtausmittauskokeita erilaisilla virtauskappaleilla putkivirtauksessa. Virtausaineena oli vesi sekä sellumassa eri sakeuksissa. Tulosten analysoinnin perusteella suoritettiin valitulla virtauskappaleella alustava koeajo prosessilaitteessa. Koelaitteen kehityksessä määritettiin ensin laitteelle tutkimukselliset tavoitteet. Erilaisia tutkimusmenetelmien arvioinnin perustella valittiin koelaitteeseen sopivat menetelmät. Tutkimuksellisten tavoitteiden ja sovellettavien menetelmien perusteella mitoitettiin ja suunniteltiin koelaite.