Quantifying Time Awake Posturographically

This thesis focuses on the issue of testing sleepiness quantitatively. The issue is relevant to policymakers concerned with traffic- and occupational safety; such testing provides a tool for safety legislation and -surveillance. The findings of this thesis provide guidelines for a posturographic sleepiness tester. Sleepiness ensuing from staying awake merely 17 h impairs our performance as much as the legally proscribed blood alcohol concentration 0.5 does. Hence, sleepiness is a major risk factor in transportation and occupational accidents. The lack of convenient, commercial sleepiness tests precludes testing impending sleepiness levels contrary to simply breath testing for alcohol intoxication. Posturography is a potential sleepiness test, since clinical diurnal balance testing suggests the hypothesis that time awake could be posturographically estimable. Relying on this hypothesis this thesis examines posturographic sleepiness testing for instrumentation purposes. Empirical results from 63 subjects for whom we tested balance with a force platform during wakefulness for maximum 36 h show that sustained wakefulness impairs balance. The results show that time awake is posturographically estimable with 88% accuracy and 97% precision which validates our hypothesis. Results also show that balance scores tested at 13:30 hours serve as a threshold to detect excessive sleepiness. Analytical results show that the test length has a marked effect on estimation accuracy: 18 s tests suffice to identify sleepiness related balance changes, but trades off some of the accuracy achieved with 30 s tests. The procedure to estimate time awake relies on equating the subject s test score to a reference table (comprising balance scores tested during sustained wakefulness, regressed against time awake). Empirical results showed that sustained wakefulness explains 60% of the diurnal balance variations, whereas the time of day explains 40% of the balance variations. The latter fact implies that time awake estimations also must rely on knowing the local times of both test and reference scores.

Testing against changing correlation

A test for time-varying correlation is developed within the framework of a dynamic conditional score (DCS) model for both Gaussian and Student t-distributions. The test may be interpreted as a Lagrange multiplier test and modified to allow for the estimation of models for time-varying volatility in the individual series. Unlike standard moment-based tests, the score-based test statistic includes information on the level of correlation under the null hypothesis and local power arguments indicate the benefits of doing so. A simulation study shows that the performance of the score-based test is strong relative to existing tests across a range of data generating processes. An application to the Hong Kong and South Korean equity markets shows that the new test reveals changes in correlation that are not detected by the standard moment-based test.

Clinical reasoning: The relative contribution of identification, interpretation and hypothesis errors to misdiagnosis

The aim of this study was to identify and describe the types of errors in clinical reasoning that contribute to poor diagnostic performance at different levels of medical training and experience. Three cohorts of subjects, second- and fourth- (final) year medical students and a group of general practitioners, completed a set of clinical reasoning problems. The responses of those whose scores fell below the 25th centile were analysed to establish the stage of the clinical reasoning process - identification of relevant information, interpretation or hypothesis generation - at which most errors occurred and whether this was dependent on problem difficulty and level of medical experience. Results indicate that hypothesis errors decrease as expertise increases but that identification and interpretation errors increase. This may be due to inappropriate use of pattern recognition or to failure of the knowledge base. Furthermore, although hypothesis errors increased in line with problem difficulty, identification and interpretation errors decreased. A possible explanation is that as problem difficulty increases, subjects at all levels of expertise are less able to differentiate between relevant and irrelevant clinical features and so give equal consideration to all information contained within a case. It is concluded that the development of clinical reasoning in medical students throughout the course of their pre-clinical and clinical education may be enhanced by both an analysis of the clinical reasoning process and a specific focus on each of the stages at which errors commonly occur.

High-quality polar UV measurements : scientific analyses and transfer of the irradiance scale

The Earth's ecosystems are protected from the dangerous part of the solar ultraviolet (UV) radiation by stratospheric ozone, which absorbs most of the harmful UV wavelengths. Severe depletion of stratospheric ozone has been observed in the Antarctic region, and to a lesser extent in the Arctic and midlatitudes. Concern about the effects of increasing UV radiation on human beings and the natural environment has led to ground based monitoring of UV radiation. In order to achieve high-quality UV time series for scientific analyses, proper quality control (QC) and quality assurance (QA) procedures have to be followed. In this work, practices of QC and QA are developed for Brewer spectroradiometers and NILU-UV multifilter radiometers, which measure in the Arctic and Antarctic regions, respectively. These practices are applicable to other UV instruments as well. The spectral features and the effect of different factors affecting UV radiation were studied for the spectral UV time series at Sodankylä. The QA of the Finnish Meteorological Institute's (FMI) two Brewer spectroradiometers included daily maintenance, laboratory characterizations, the calculation of long-term spectral responsivity, data processing and quality assessment. New methods for the cosine correction, the temperature correction and the calculation of long-term changes of spectral responsivity were developed. Reconstructed UV irradiances were used as a QA tool for spectroradiometer data. The actual cosine correction factor was found to vary between 1.08-1.12 and 1.08-1.13. The temperature characterization showed a linear temperature dependence between the instrument's internal temperature and the photon counts per cycle. Both Brewers have participated in international spectroradiometer comparisons and have shown good stability. The differences between the Brewers and the portable reference spectroradiometer QASUME have been within 5% during 2002-2010. The features of the spectral UV radiation time series at Sodankylä were analysed for the time period 1990-2001. No statistically significant long-term changes in UV irradiances were found, and the results were strongly dependent on the time period studied. Ozone was the dominant factor affecting UV radiation during the springtime, whereas clouds played a more important role during the summertime. During this work, the Antarctic NILU-UV multifilter radiometer network was established by the Instituto Nacional de Meteorogía (INM) as a joint Spanish-Argentinian-Finnish cooperation project. As part of this work, the QC/QA practices of the network were developed. They included training of the operators, daily maintenance, regular lamp tests and solar comparisons with the travelling reference instrument. Drifts of up to 35% in the sensitivity of the channels of the NILU-UV multifilter radiometers were found during the first four years of operation. This work emphasized the importance of proper QC/QA, including regular lamp tests, for the multifilter radiometers also. The effect of the drifts were corrected by a method scaling the site NILU-UV channels to those of the travelling reference NILU-UV. After correction, the mean ratios of erythemally-weighted UV dose rates measured during solar comparisons between the reference NILU-UV and the site NILU-UVs were 1.007±0.011 and 1.012±0.012 for Ushuaia and Marambio, respectively, when the solar zenith angle varied up to 80°. Solar comparisons between the NILU-UVs and spectroradiometers showed a ±5% difference near local noon time, which can be seen as proof of successful QC/QA procedures and transfer of irradiance scales. This work also showed that UV measurements made in the Arctic and Antarctic can be comparable with each other.

Seismic response of wrap-faced reinforced soil-retaining wall models using shaking table tests

This paper presents the results of shaking table tests on geotextile-reinforced wrap-faced soil-retaining walls. Construction of model retaining walls in a laminar box mounted on a shaking table, instrumentation, and results from the shaking table tests are discussed in detail. The base motion parameters, surcharge pressure and number of reinforcing layers are varied in different model tests. It is observed from these tests that the response of the wrap-faced soil-retaining walls is significantly affected by the base acceleration levels, frequency of shaking, quantity of reinforcement and magnitude of surcharge pressure on the crest. The effects of these different parameters on acceleration response at different elevations of the retaining wall, horizontal soil pressures and face deformations are also presented. The results obtained from this study are helpful in understanding the relative performance of reinforced soil-retaining walls under different test conditions used in the experiments.

Diagnostic Tests Based on Quantile Residuals for Nonlinear Time Series Models

This thesis studies quantile residuals and uses different methodologies to develop test statistics that are applicable in evaluating linear and nonlinear time series models based on continuous distributions. Models based on mixtures of distributions are of special interest because it turns out that for those models traditional residuals, often referred to as Pearson's residuals, are not appropriate. As such models have become more and more popular in practice, especially with financial time series data there is a need for reliable diagnostic tools that can be used to evaluate them. The aim of the thesis is to show how such diagnostic tools can be obtained and used in model evaluation. The quantile residuals considered here are defined in such a way that, when the model is correctly specified and its parameters are consistently estimated, they are approximately independent with standard normal distribution. All the tests derived in the thesis are pure significance type tests and are theoretically sound in that they properly take the uncertainty caused by parameter estimation into account. -- In Chapter 2 a general framework based on the likelihood function and smooth functions of univariate quantile residuals is derived that can be used to obtain misspecification tests for various purposes. Three easy-to-use tests aimed at detecting non-normality, autocorrelation, and conditional heteroscedasticity in quantile residuals are formulated. It also turns out that these tests can be interpreted as Lagrange Multiplier or score tests so that they are asymptotically optimal against local alternatives. Chapter 3 extends the concept of quantile residuals to multivariate models. The framework of Chapter 2 is generalized and tests aimed at detecting non-normality, serial correlation, and conditional heteroscedasticity in multivariate quantile residuals are derived based on it. Score test interpretations are obtained for the serial correlation and conditional heteroscedasticity tests and in a rather restricted special case for the normality test. In Chapter 4 the tests are constructed using the empirical distribution function of quantile residuals. So-called Khmaladze s martingale transformation is applied in order to eliminate the uncertainty caused by parameter estimation. Various test statistics are considered so that critical bounds for histogram type plots as well as Quantile-Quantile and Probability-Probability type plots of quantile residuals are obtained. Chapters 2, 3, and 4 contain simulations and empirical examples which illustrate the finite sample size and power properties of the derived tests and also how the tests and related graphical tools based on residuals are applied in practice.

The effects of marriage partners' socio-economic positions on the risk of divorce in Finland

Väitöskirjatutkimuksen tavoitteena oli selvittää, miten aviopuolisoiden sosioekonominen asema vaikuttaa avioeroriskiin Suomessa. Tutkimuksessa käytettiin Tilastokeskuksen rekistereistä koottua aineistoa, joka koskee suomalaisten ensimmäisiä avioliittoja vuoden 1990 lopussa ja avioeroja vuosina 1991−93. Väitöskirjaan sisältyy kolme osatutkimusta. Ensimmäinen osatutkimus käsitteli avioeroriskin vaihtelua aviopuolisoiden sosioekonomisen aseman eri osatekijöiden (koulutusaste, sosiaaliryhmä, pääasiallinen toiminta, tulotaso, asunnon omistaminen ja asumisahtaus) mukaan. Kaiken kaikkiaan avioeroriski oli sitä pienempi, mitä paremmassa taloudellisessa ja sosiaalisessa asemassa aviopuolisot olivat. Esimerkiksi miehen ja vaimon korkea koulutusaste, toimihenkilöammatti, työssäkäynti (etenkin verrattuna työttömyyteen) sekä omistusasunnossa asuminen liittyivät pienentyneeseen avioeroriskiin. Vaimon sosioekonomisen aseman yhteys avioeroriskiin oli paljolti samanlainen kuin miehen aseman yhteys. Huomattavin poikkeus tähän oli, että vaimon suuret tulot lisäsivät avioeroriskiä, vaikka miehen suurilla tuloilla oli päinvastainen vaikutus. Lisäksi kotitaloustyötä pääasiallisena toimintanaan tekevillä naisilla (pääasiallisen toiminnan luokka ”muut”) oli vielä pienempi avioeroriski kuin työssäkäyvillä naisilla. Toisessa osatutkimuksessa keskityttiin aviomiehen ja vaimon aseman yhdistettyyn vaikutukseen. Selviä viitteitä siitä, että puolisoiden koulutustasojen erilaisuus lisäisi eroriskiä, ei saatu. Pareilla, joissa molemmilla oli enintään perusasteen koulutus, oli kuitenkin odotettua pienempi avioeroriski. Eroriski oli suhteellisen alhainen pareilla, joissa vaimo oli työssäkäyvä tai kotitaloustyötä tekevä ja aviomies työssäkäyvä. Eroriskiä kasvatti se, että aviomies, vaimo tai molemmat puolisot olivat työttömiä. Vaimon korkea tulotaso lisäsi eroriskiä miehen kaikilla tulotasoilla mutta erityisen voimakkaasti silloin, kun miehen tulotaso oli alhainen. Kolmanneksi selvitettiin, vaikuttaako puolisoiden sosioekonominen asema avioeroriskiin eri tavalla riippuen siitä, kauanko avioliitto on kestänyt. Tällöin havaittiin, että vähän koulutettujen ja työntekijäammateissa toimivien puolisoiden suuri eroriski rajoittuu paljolti nuorimpiin avioliittoihin. Sen sijaan esim. puolisoiden työttömyys, vaimon korkea tulotaso ja vuokra-asunnossa asuminen kasvattivat eroriskiä riippumatta siitä, kuinka kauan avioliitto oli kestänyt. Kaiken kaikkiaan eroriski oli siis sitä pienempi, mitä paremmassa taloudellisessa ja sosiaalisessa asemassa puolisot olivat. Vaimon taloudellisilla ja sosiaalisilla resursseilla näyttää kuitenkin olevan myös joitakin avioeroriskiä lisääviä vaikutuksia.

Tests of a Roman Pot Prototype for the TOTEM Experiment

The TOTEM collaboration has developed and tested the first prototype of its Roman Pots to be operated in the LHC. TOTEM Roman Pots contain stacks of 10 silicon detectors with strips oriented in two orthogonal directions. To measure proton scattering angles of a few microradians, the detectors will approach the beam centre to a distance of 10 sigma + 0.5 mm (= 1.3 mm). Dead space near the detector edge is minimised by using two novel "edgeless" detector technologies. The silicon detectors are used both for precise track reconstruction and for triggering. The first full-sized prototypes of both detector technologies as well as their read-out electronics have been developed, built and operated. The tests took place first in a fixed-target muon beam at CERN's SPS, and then in the proton beam-line of the SPS accelerator ring. We present the test beam results demonstrating the successful functionality of the system despite slight technical shortcomings to be improved in the near future.

Loading of itraconazole into porous silica and silicon microparticles: characterization and dissolution tests

Most new drug molecules discovered today suffer from poor bioavailability. Poor oral bioavailability results mainly from poor dissolution properties of hydrophobic drug molecules, because the drug dissolution is often the rate-limiting event of the drug’s absorption through the intestinal wall into the systemic circulation. During the last few years, the use of mesoporous silica and silicon particles as oral drug delivery vehicles has been widely studied, and there have been promising results of their suitability to enhance the physicochemical properties of poorly soluble drug molecules. Mesoporous silica and silicon particles can be used to enhance the solubility and dissolution rate of a drug by incorporating the drug inside the pores, which are only a few times larger than the drug molecules, and thus, breaking the crystalline structure into a disordered, amorphous form with better dissolution properties. Also, the high surface area of the mesoporous particles improves the dissolution rate of the incorporated drug. In addition, the mesoporous materials can also enhance the permeability of large, hydrophilic drug substances across biological barriers. T he loading process of drugs into silica and silicon mesopores is mainly based on the adsorption of drug molecules from a loading solution into the silica or silicon pore walls. There are several factors that affect the loading process: the surface area, the pore size, the total pore volume, the pore geometry and surface chemistry of the mesoporous material, as well as the chemical nature of the drugs and the solvents. Furthermore, both the pore and the surface structure of the particles also affect the drug release kinetics. In this study, the loading of itraconazole into mesoporous silica (Syloid AL-1 and Syloid 244) and silicon (TOPSi and TCPSi) microparticles was studied, as well as the release of itraconazole from the microparticles and its stability after loading. Itraconazole was selected for this study because of its highly hydrophobic and poorly soluble nature. Different mesoporous materials with different surface structures, pore volumes and surface areas were selected in order to evaluate the structural effect of the particles on the loading degree and dissolution behaviour of the drug using different loading parameters. The loaded particles were characterized with various analytical methods, and the drug release from the particles was assessed by in vitro dissolution tests. The results showed that the loaded drug was apparently in amorphous form after loading, and that the loading process did not alter the chemical structure of the silica or silicon surface. Both the mesoporous silica and silicon microparticles enhanced the solubility and dissolution rate of itraconazole. Moreover, the physicochemical properties of the particles and the loading procedure were shown to have an effect on the drug loading efficiency and drug release kinetics. Finally, the mesoporous silicon particles loaded with itraconazole were found to be unstable under stressed conditions (at 38 qC and 70 % relative humidity).

Effect of relative density and confining pressure on Poisson ratio from bender and extender elements tests

By using the bender and extender elements tests, together with measurements of the travel times of shear (S) and primary (P) waves, the variation of Poisson ratio (nu) was determined for dry sands with respect to changes in relative densities and effective confining pressures (sigma(3)). The tests were performed for three different ranges of particle sizes. The magnitude of the Poisson ratio decreases invariably with an increase in both the relative density and the effective confining pressure. The effect of the confining pressure on the Poisson ratio was found to become relatively more significant for fine-grained sand as compared with the coarse-grained sand. For a given material, at a particular value of sigma(3), the magnitude of the Poisson ratio decreases, almost in a linear fashion, with an increase in the value of maximum shear modulus (G(max)). The two widely used correlations in literature, providing the relationships among G(max), void ratio (e) and effective confining pressure (sigma(3)), applicable for angular granular materials, were found to compare reasonably well with the present experimental data for the fine- and medium-grained sands. However, for the coarse-grained sand, these correlations tend to overestimate the values of G(max).

Export of proteins across membranes: The helix reversion hypothesis

A model is presented which explains the biological role of the leader peptide in protein export. Along the lines of this model, the conformational changes of a protein with environment serves as a general mechanism for translocation. The leader peptide in the cytoplasm takes a hairpin like conformation which reverts to an extended helix upon integration into the membrane. The essential features of this model are in accord with recent results of protein export.