Stress in Laboratory Animal Studies: Preconceptions Misconceptions

Abstract not availabl

Problems in density estimation for independent and dependent data

The aim of this thesis is to provide two extensions to the theory of nonparametric kernel density estimation that increase the scope of the technique. The basic ideas of kernel density estimation are not new, having been proposed by Rosenblatt [20] and extended by Parzen [17]. The objective is that for a given set of data, estimates of functions of the distribution of the data such as probability densities are derived without recourse to rigid parametric assumptions and allow the data themselves to be more expressive in the statistical outcome. Thus kernel estimation has captured the imagination of statisticians searching for more flexibility and eager to utilise the computing revolution. The abundance of data and computing power have revealed distributional shapes that are difficult to model by traditional parametric approaches and in this era, the computer intensive technique of kernel estimation can be performed routinely. Also we are aware that computing power can be harnessed to give improved statistical analyses. Thus a lot of modern statistical research involves kernel estimation from complex data sets and our research is concordant with that momentum. The thesis contains three chapters. In Chapter 1 we provide an introduction to kernel density estimation and we give an outline to our two research topics. Our first extension to the theory is given in Chapter 2 where we investigate density estimation from independent data, using high order kernel functions. These kernel functions are designed for bias reduction but they have the penalty of yielding negative density estimates where data are sparse. In common practice, the negative estimates would arise in the tails of the density and we provide four ways of correcting this negativity to give bona fide estimates of the probability density. Our theory shows that the effects of these corrections are asymptotically negligible and thus opens the way for the regular use of bias reducing, high order kernel functions. We also consider density estimation of continuous stationary stochastic processes and this is the content of Chapter 3. With this problem, the dependent nature of the data influences the accuracy of the kernel density estimator and we provide theory regarding the convergence of the kernel estimators of the density and its derivatives to the true functions. An important result from this study is that nonparametric density estimators from dependent processes can have the same rates of convergence as their parametric counterparts yet retain the flexibility of being independent of parametric assumptions. Our other results indicate that the convergence rate of the density estimator can be quite slow if there are large lag dependencies amongst the data and suggests that large samples would be required for reliable inference about such data. The flexibility of kernel density estimation for continuous and discrete data, independent and dependent observations, means that it is a useful statistical tool. The techniques given in this thesis are not restricted to the analysis of simple sets of data but may be employed in the construction of statistical models for complex data with a high degree of structure

Heart rate variability and cortisol responses during attentional and working memory tasks in naval cadets

The aim of the project was to study the relationship between heart rate variability (HRV) and cortisol release during cognitive challenging tasks. Forty-nine male naval cadets from the Royal Norwegian Naval Academy were administered computerised versions of attentional and working memory tests. The results from this study support the hypothesis of a negative correlation between HRV and cortisol secretion during cognitive tasks. Confirmation of the hypothesis with the low HRV group scoring higher on cortisol only during performance of cognitive tasks and recovery was also found. Furthermore, a replication of the previous findings of a negative association between cortisol levels and performance were supported when using uncorrected comparisons. None of the correlations survived Bonferonin corrections. The findings are discussed in relation to factors increasing HRV thus improving tolerance to cognitive stress in onboard environments.publishedVersio

Heart rate variability and cortisol responses during attentional and working memory tasks in naval cadets

The aim of the paper was to study the relationship between heart rate variability (HRV) and cortisol release during cognitive challenging tasks. Forty-nine male naval cadets from the Royal Norwegian Naval Academy were administered computerised versions of attentional and working memory tests. The results from this study support the hypothesis of a negative correlation between HRV and cortisol secretion during cognitive tasks. Confirmation of the hypothesis with the low HRV group scoring higher on cortisol only during performance of cognitive tasks and recovery was also found. Furthermore, a replication of the previous findings of a negative association between cortisol levels and performance were supported when using uncorrected comparisons. None of the correlations survived Bonferonin corrections. The findings are discussed in relation to factors increasing HRV, thus improving tolerance to cognitive stress in onboard environments

Intestinal permeability and faecal Granulocyte Marker Protein in Dextran Sulphate Sodium - induced colitis in rats

The aims of this preliminary study were to foster the development of an animal model of inflammatory bowel disease (IBD). We hereby studied the effects of dextran sulphate sodium (DSS) in drinking water on (a) intestinal permeability and (b) faecal levels of granulocyte marker protein (GMP) in rats. Methods were adopted to keep stress at a minimum. The animals had free access to DSS for 36 or 96 hrs. Controls received only water. Oral administration of 51Cr-labelled ethylenediaminetetraacetic acid (51CrEDTA) is used for clinical evaluation of intestinal permeability in IBD. 51CrEDTA was administered by training the animals to drink a given quantity of fluid within 5 minutes in a specific environment. On the test day, they voluntarily consumed 1 ml water containing 2 μCi 51CrEDTA. Urine samples were taken from filter paper in their home-cages for 6 hrs and radioactivity measured in a gamma counter. Faecal samples were collected after 36 and 96 hrs on DSS or water for GMP analysis. RESULTS: GMP was elevated in the DSSinduced animals after both 36 hrs (p<.05) and 96 hrs (p<.01), the elevation being greater after 96 hrs. Consumption of DSS increased the urinary excretion of 51CrEDTA after 36 hrs, but not after 96 hrs. Only DSS consumption for 96 hrs resulted in visible colonic erosions in either the proximal, mid or distal part of the colon. CONCLUSION: DSS has an acute effect upon urinary excretion of 51CrEDTA, and 96 hrs of access to DSS is sufficient to induce elevated GMP levels and colonic erosions in adult rats

Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models.publishedVersio

Multi-Scale Methods Applied to Small-Angle X-Ray Scattering Images of Breast Tumour Tissue

This thesis develops statistical methods for investigating small angle x-ray scattering (SAXS) images of breast tissue of three different pathologies: normal, benign and malignant. The objective was to thoroughly examine the images and detect those features indicative of malignancy. The tissue sample which is the source of the SAXS image is approximately ten millimetres long and one millimetre wide. In comparison, the structures of interest are on the nanometre scale and therefore we would expect that in practice each sample is a mixture of the different tissue pathologies. This mixture of different pathologies will have a bearing on the overall classification of the sample. Conventional classification models will tend to use data that has been reduced to those components that show the most variation. However in this case, even trivial amounts of feature suggestive of malignancy must be retained as they might be influential in the classification of tissue type. The mathematical strategy adopted in this thesis relied on a series of transforms along with the resulting interpretation of their coefficients. An adaptive transform that used a range of filter functions was applied to the SAXS images. The coefficients from this transform that had an acceptable probability of misclassification were retained and the others rejected

Stellar Astrophysics with a Dispersed Fourier Transform Spectrograph. II. Orbits of Double-lined Spectroscopic Binaries

We present orbital parameters for six double-lined spectroscopic binaries (iota Pegasi, omega Draconis, 12 Bootis, V1143 Cygni, beta Aurigae, and Mizar A) and two double-lined triple star systems (kappa Pegasi and eta Virginis). The orbital fits are based upon high-precision radial velocity observations made with a dispersed Fourier Transform Spectrograph, or dFTS, a new instrument which combines interferometric and dispersive elements. For some of the double-lined binaries with known inclination angles, the quality of our RV data permits us to determine the masses M_1 and M_2 of the stellar components with relative errors as small as 0.2%.Comment: 41 pages, 8 figures, accepted by A

The Full-sky Astrometric Mapping Explorer -- Astrometry for the New Millennium

FAME is designed to perform an all-sky, astrometric survey with unprecedented accuracy. It will create a rigid astrometric catalog of 4x10^7 stars with 5 < m_V < 15. For bright stars, 5 < m_V < 9, FAME will determine positions and parallaxes accurate to < 50 microarcseconds, with proper motion errors < 50 microarcseconds/year. For fainter stars, 9 < m_V < 15, FAME will determine positions and parallaxes accurate to < 500 microarcseconds, with proper motion errors < 500 microarcseconds/year. It will also collect photometric data on these 4 x 10^7 stars in four Sloan DSS colors.Comment: 6 pages, 4 figures, to appear in "Working on the Fringe

Astrophysical Adaptation of Points, the Precision Optical Interferometer in Space

POINTS (Precision Optical INTerferometer in Space) would perform microarcsecond optical astrometric measurements from space, yielding submicroarcsecond astrometric results from the mission. It comprises a pair of independent Michelson stellar interferometers and a laser metrology system that measures both the critical starlight paths and the angle between the baselines. The instrument has two baselines of 2 m, each with two subapertures of 35 cm; by articulating the angle between the baselines, it observes targets separated by 87 to 93 deg. POINTS does global astrometry, i.e., it measures widely separated targets, which yields closure calibration, numerous bright reference stars, and absolute parallax. Simplicity, stability, and the mitigation of systematic error are the central design themes. The instrument has only three moving-part mechanisms, and only one of these must move with sub-milliradian precision; the other two can tolerate a precision of several tenths of a degree. Optical surfaces preceding the beamsplitter or its fold flat are interferometrically critical; on each side of the interferometer, there are only three such. Thus, light loss and wavefront distortion are minimized. POINTS represents a minimalistic design developed ab initio for space. Since it is intended for astrometry, and therefore does not require the u-v-plane coverage of an imaging, instrument, each interferometer need have only two subapertures. The design relies on articulation of the angle between the interferometers and body pointing to select targets; the observations are restricted to the 'instrument plane.' That plane, which is fixed in the pointed instrument, is defined by the sensitive direction for the two interferometers. Thus, there is no need for siderostats and moving delay lines, which would have added many precision mechanisms with rolling and sliding parts that would be required to function throughout the mission. Further, there is no need for a third interferometer, as is required when out-of-plane observations are made. An instrument for astrometry, unlike those for imaging, can be compact and yet scientifically productive. The POINTS instrument is compact and therefore requires no deployment of precision structures, has no low-frequency (i.e., under 100 Hz) vibration modes, and is relatively easy to control thermally. Because of its small size and mass, it is easily and quickly repointed between observations. Further, because of the low mass, it can be economically launched into high Earth orbit which, in conjunction with a solar shield, yields nearly unrestricted sky coverage and a stable thermal environment