Assessment of Risk for Type 1 Diabetes in Children of Affected Families and in the General Population : Role of Immunological and Metabolic Markers

Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.

Light scattering in random media with wavelength-scale structures : astronomical and industrial applications

Light scattering, or scattering and absorption of electromagnetic waves, is an important tool in all remote-sensing observations. In astronomy, the light scattered or absorbed by a distant object can be the only source of information. In Solar-system studies, the light-scattering methods are employed when interpreting observations of atmosphereless bodies such as asteroids, atmospheres of planets, and cometary or interplanetary dust. Our Earth is constantly monitored from artificial satellites at different wavelengths. With remote sensing of Earth the light-scattering methods are not the only source of information: there is always the possibility to make in situ measurements. The satellite-based remote sensing is, however, superior in the sense of speed and coverage if only the scattered signal can be reliably interpreted. The optical properties of many industrial products play a key role in their quality. Especially for products such as paint and paper, the ability to obscure the background and to reflect light is of utmost importance. High-grade papers are evaluated based on their brightness, opacity, color, and gloss. In product development, there is a need for computer-based simulation methods that could predict the optical properties and, therefore, could be used in optimizing the quality while reducing the material costs. With paper, for instance, pilot experiments with an actual paper machine can be very time- and resource-consuming. The light-scattering methods presented in this thesis solve rigorously the interaction of light and material with wavelength-scale structures. These methods are computationally demanding, thus the speed and accuracy of the methods play a key role. Different implementations of the discrete-dipole approximation are compared in the thesis and the results provide practical guidelines in choosing a suitable code. In addition, a novel method is presented for the numerical computations of orientation-averaged light-scattering properties of a particle, and the method is compared against existing techniques. Simulation of light scattering for various targets and the possible problems arising from the finite size of the model target are discussed in the thesis. Scattering by single particles and small clusters is considered, as well as scattering in particulate media, and scattering in continuous media with porosity or surface roughness. Various techniques for modeling the scattering media are presented and the results are applied to optimizing the structure of paper. However, the same methods can be applied in light-scattering studies of Solar-system regoliths or cometary dust, or in any remote-sensing problem involving light scattering in random media with wavelength-scale structures.

The SPHERE Study: Secondary prevention of heart disease in general practice: protocol of a randomised controlled trial of tailored practice and patient care plans with parallel qualitative, economic and policy analyses. [ISRCTN24081411]

Background: The aim of the SPHERE study is to design, implement and evaluate tailored practice and personal care plans to improve the process of care and objective clinical outcomes for patients with established coronary heart disease (CHD) in general practice across two different health systems on the island of Ireland.CHD is a common cause of death and a significant cause of morbidity in Ireland. Secondary prevention has been recommended as a key strategy for reducing levels of CHD mortality and general practice has been highlighted as an ideal setting for secondary prevention initiatives. Current indications suggest that there is considerable room for improvement in the provision of secondary prevention for patients with established heart disease on the island of Ireland. The review literature recommends structured programmes with continued support and follow-up of patients; the provision of training, tailored to practice needs of access to evidence of effectiveness of secondary prevention; structured recall programmes that also take account of individual practice needs; and patient-centred consultations accompanied by attention to disease management guidelines.

Methods: SPHERE is a cluster randomised controlled trial, with practice-level randomisation to intervention and control groups, recruiting 960 patients from 48 practices in three study centres (Belfast, Dublin and Galway). Primary outcomes are blood pressure, total cholesterol, physical and mental health status (SF-12) and hospital re-admissions. The intervention takes place over two years and data is collected at baseline, one-year and two-year follow-up. Data is obtained from medical charts, consultations with practitioners, and patient postal questionnaires. The SPHERE intervention involves the implementation of a structured systematic programme of care for patients with CHD attending general practice. It is a multi-faceted intervention that has been developed to respond to barriers and solutions to optimal secondary prevention identified in preliminary qualitative research with practitioners and patients. General practitioners and practice nurses attend training sessions in facilitating behaviour change and medication prescribing guidelines for secondary prevention of CHD. Patients are invited to attend regular four-monthly consultations over two years, during which targets and goals for secondary prevention are set and reviewed. The analysis will be strengthened by economic, policy and qualitative components.

General local and rectilinear vibrational coordinates consistent with Eckart's conditions

We present a general method to construct a set of local rectilinear vibrational coordinates for a nonlinear molecule whose reference structure does not necessarily correspond to a stationary point of the potential-energy surface. We show both analytically and with a numerical example that the vibrational coordinates satisfy Eckart's conditions. In addition, we find that the Watson Hamiltonian provides a fairly robust description even of highly excited vibrational states of triatomic molecules, except for a few states of large amplitude motion sampling the singular region of the Hamiltonian. These states can be identified through slow convergence.

A randomized follow-up study of the general health and quality of life of an elderly edentulous population wearing either mandibular two-implant overdentures or conventional dentures

L’augmentation de la population âgée dans la société indique que les systèmes de soins de la santé font face à de nouveaux défis. Les hauts niveaux d’incapacité qui en résultent peuvent être réduits par les nouvelles technologies, la promotion de la santé ainsi que des stratégies de prévention. Les écrits scientifiques récents soulignent la supériorité des prothèses dentaires implanto-portées par rapport aux prothèses conventionnelles en termes de satisfaction et de qualité de la vie des patients. Cependant, il n'est toujours pas clair si ces avantages ont des effets positifs à long terme sur la santé orale et générale ainsi que sur la qualité de vie des populations âgées. Objectifs, Hypothèses : Notre but était de mesurer l’impact des prothèses mandibulaires retenues par 2 implants sur la qualité de vie associée à la santé bucco-dentaire et générale ainsi que sur la santé orale et la qualité du sommeil des aînés édentés. Nous avons évalué les hypothèses nulles suivantes : il n'y a aucune différence entre les individus portants des prothèses mandibulaires retenues par 2 implants (IODs) et ceux qui portent des prothèses conventionnelles (CDs), par rapport à la qualité de vie reliée à la santé bucco-dentaire et générale, la santé orale et la qualité du sommeil, un an après avoir reçu leurs nouvelles prothèses. Méthodes : Dans cette étude randomisée contrôlée, 255 aînés ont reçu au hasard IODs ou les CDs, les deux types de prothèses étant opposés à des prothèses maxillaires conventionnelles. La qualité de la vie reliée à la santé bucco-dentaire (OHRQoL) et la santé générale subjective ont été mesurées avec les questionnaires Oral Health Impact Profile (OHIP-20) et Short Form-36 (SF-36) en condition pré-traitement et après un an. La qualité du sommeil et la somnolence diurne ont été mesurées à l’aide du questionnaire Qualité de Sommeil de Pittsburg et de l'Échelle de Somnolence Epworth. La santé orale a été évaluée par un examen clinique. Les variables indépendantes étaient le sens de cohérence et le type de prosthèse, ainsi que des variables socio-démographiques. En utilisant des analyses statistiques bi et multi-factorielles, des comparaisons à l’intérieur d’un même groupe et entre deux groupes ont été effectuées. Résultats : Les différences pré et post traitement pour les cotes OHIP étaient significativement plus grandes pour le groupe IOD que le groupe CD (p<0.05). Le type de traitement et la cote pré-traitement étaient des facteurs significatifs à OHRQoL (p < 0.0001). Dans le groupe CD, il y avait une diminution significative par rapport aux cotes de «Physical Component Scores (PCS)», le fonctionnement physique, le rôle physique et la douleur physique entre les données pré-traitement et un an après le traitement, ce qui indique une diminution au niveau de la santé générale subjective. Dans le groupe IOD, une diminution statistiquement non significative a été remarquée par rapport à toutes les cotes des sous-échelles de SF-36, sauf pour la douleur physique. Le modèle final de régression a démontré qu’après ajustement pour les variables âge, sexe, statut marital et type de traitement, la cote totale finale d’OHIP et les données de bases de PCS prédisaient la cote finale de PCS (p < 0.0001). Aucune corrélation significative entre sens de cohérence et OHRQoL n'a été détectée (r =-0.1; p > 0.05). Les aînés porteurs des prothèses conventionnelles avaient presque 5 fois plus de chance d’avoir une stomatite prothétique que ceux portant des prothèses mandibulaires hybrides retenues par 2 implants (p < 0.0001). Les aînés ayant subjectivement une mauvaise santé générale avaient une qualité de sommeil moins bonne que ceux avec une meilleure santé générale subjective (p < 0.05). Les personnes qui avaient une OHRQoL moins bonne étaient presque 4 fois plus somnolentes pendant le jour que celles avec une meilleure OHRQoL (p=0.003, χ2; OR =3.8 CI 1.5 to 9.8). L'analyse de régression a montré que la santé générale subjective et OHRQoL prévoient la qualité du sommeil (p=0.022 et p=0.001, respectivement) et la somnolence diurne (p=0.017 et p=0.005, respectivement). Conclusions: Les résultats de cette étude suggèrent que, chez les aînés édentés, des prothèses mandibulaires hybrides retenues par deux implants amènent une amélioration significative de la qualité de vie reliée à la santé bucco-dentaire et maintiennent la sensation d’une meilleure santé physique. Des prothèses hybrides implanto-portées peuvent contribuer à la santé orale en réduisant les traumatismes infligés à la muqueuse orale et en contrôlant la stomatite prothétique. Les aînés édentés dont le niveau de qualité de vie reliée à la santé bucco-dentaire est bas, peuvent aussi avoir des troubles de qualité du sommeil.

Near-Earth asteroid binaries in close encounters with the Earth

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stability and dynamics of terrestrial planets in binary star systems: application on Alpha Centauri

Binary stars are frequent in the universe, with about 50% of the known main sequence stars being located at a multiple star system (Abt, 1979). Even though, they are universally thought as second rate sites for the location of exo-planets and the habitable zone, due to the difficulties of detection and high perturbation that could prevent planet formation and long term stability. In this work we show that planets in binary star systems can have regular orbits and remain on the habitable zone. We introduce a stability criterium based on the solution of the restricted three body problem and apply it to describe the short period planar and three-dimentional stability zones of S-type orbits around each star of the Alpha Centauri system. We develop as well a semi-analytical secular model to study the long term dynamics of fictional planets in the habitable zone of those stars and we verify that planets on the habitable zone would be in regular orbits with any eccentricity and with inclination to the binary orbital plane up until 35 degrees. We show as well that the short period oscillations on the semi-major axis is 100 times greater than the Earth's, but at all the time the planet would still be found inside the Habitable zone.

Pupil phase apodization for achromatic imaging of extra-solar planets

Direct imaging of extra-solar planets in the visible and infrared region has generated great interest among scientists and the general public as well. However, this is a challenging problem. Diffculties of detecting a planet (faint source) are caused, mostly, by two factors: sidelobes caused by starlight diffraction from the edge of the pupil and the randomly scattered starlight caused by the phase errors from the imperfections in the optical system. While the latter diffculty can be corrected by high density active deformable mirrors with advanced phase sensing and control technology, the optimized strategy for suppressing the diffraction sidelobes is still an open question. In this thesis, I present a new approach to the sidelobe reduction problem: pupil phase apodization. It is based on a discovery that an anti-symmetric spatial phase modulation pattern imposed over a pupil or a relay plane causes diffracted starlight suppression sufficient for imaging of extra-solar planets. Numerical simulations with specific square pupil (side D) phase functions, such as ... demonstrate annulling in at least one quadrant of the diffraction plane to the contrast level of better than 10^12 with an inner working angle down to 3.5L/D (with a = 3 and e = 10^3). Furthermore, our computer experiments show that phase apodization remains effective throughout a broad spectrum (60% of the central wavelength) covering the entire visible light range. In addition to the specific phase functions that can yield deep sidelobe reduction on one quadrant, we also found that a modified Gerchberg-Saxton algorithm can help to find small sized (101 x 101 element) discrete phase functions if regional sidelobe reduction is desired. Our simulation shows that a 101x101 segmented but gapless active mirror can also generate a dark region with Inner Working Distance about 2.8L/D in one quadrant. Phase-only modulation has the additional appeal of potential implementation via active segmented or deformable mirrors, thereby combining compensation of random phase aberrations and diffraction halo removal in a single optical element.

General Geology and Mines of Northwestern Montana

The five counties discussed in this paper compose the northernmost and westernmost counties in Montana. On the eastern boundary are Glacier National Park and the Continental Divide; on the southern boundary are Missoula and Powell counties; Idaho lies on the southwestern and western side; and the Canadian border lies along the northern edge. The region is on the Pacific Ocean side of the Rocky Mountains. Three major rivers, the Clark Fork, the Flathead, and the Kootenai drain this area into the Columbia River.

Can we constrain the interior structure of rocky exoplanets from mass and radius measurements?

Aims. We present an inversion method based on Bayesian analysis to constrain the interior structure of terrestrial exoplanets, in the form of chemical composition of the mantle and core size. Specifically, we identify what parts of the interior structure of terrestrial exoplanets can be determined from observations of mass, radius, and stellar elemental abundances. Methods. We perform a full probabilistic inverse analysis to formally account for observational and model uncertainties and obtain confidence regions of interior structure models. This enables us to characterize how model variability depends on data and associated uncertainties. Results. We test our method on terrestrial solar system planets and find that our model predictions are consistent with independent estimates. Furthermore, we apply our method to synthetic exoplanets up to 10 Earth masses and up to 1.7 Earth radii, and to exoplanet Kepler-36b. Importantly, the inversion strategy proposed here provides a framework for understanding the level of precision required to characterize the interior of exoplanets. Conclusions. Our main conclusions are (1) observations of mass and radius are sufficient to constrain core size; (2) stellar elemental abundances (Fe, Si, Mg) are principal constraints to reduce degeneracy in interior structure models and to constrain mantle composition; (3) the inherent degeneracy in determining interior structure from mass and radius observations does not only depend on measurement accuracies, but also on the actual size and density of the exoplanet. We argue that precise observations of stellar elemental abundances are central in order to place constraints on planetary bulk composition and to reduce model degeneracy. We provide a general methodology of analyzing interior structures of exoplanets that may help to understand how interior models are distributed among star systems. The methodology we propose is sufficiently general to allow its future extension to more complex internal structures including hydrogen- and water-rich exoplanets.

Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID

Coactivators previously implicated in ligand-dependent activation functions by thyroid hormone receptor (TR) include p300 and CREB-binding protein (CBP), the steroid receptor coactivator-1 (SRC-1)-related family of proteins, and the multicomponent TR-associated protein (TRAP) complex. Here we show that two positive cofactors (PC2 and PC4) derived from the upstream stimulatory activity (USA) cofactor fraction act synergistically to mediate thyroid hormone (T3)-dependent activation either by TR or by a TR-TRAP complex in an in vitro system reconstituted with purified factors and DNA templates. Significantly, the TRAP-mediated enhancement of activation by TR does not require the TATA box-binding protein-associated factors of TFIID. Furthermore, neither the pleiotropic coactivators CBP and p300 nor members of the SRC-1 family were detected in either the TR-TRAP complex or the other components of the in vitro assay system. These results show that activation by TR at the level of naked DNA templates is enhanced by cooperative functions of the TRAP coactivators and the general coactivators PC2 and PC4, and they further indicate a potential functional redundancy between TRAPs and TATA box-binding protein-associated factors in TFIID. In conjunction with earlier studies on other nuclear receptor-interacting cofactors, the present study also suggests a multistep pathway, involving distinct sets of cofactors, for activation of hormone responsive genes.

Martine's hand-book of etiquette and guide to true politeness : a complete manual for those who desire to understand the rules of good breeding, the customs of good society, and to avoid incorrect and vulgar habits : containing clear and comprehensive directions for correct manners, dress, and conversation, instructions for good behavior at dinner parties and the table : together with the etiquette of the ball and assembly room, evening parties, deportment in the street and when traveling, and the usage to be observed when visiting or receiving calls : to which is added the etiquette of courtship, marriage, domestic duties, and fifty-six rules to be observed in general society /

"Almost every gentleman has wine at his table whenever he has invited guests"-- p. [74].

General management plan : Glacier Bay National Park and Preserve, Alaska.

"NPS D-2034A"--Colophon.

General geology, classification, and use of clays, and use of bentonite as a lower-cost canal lining material /

Mode of access: Internet.

Report and recommendations to Governor ... and the ... Illinois General Assembly /

Description based on: 77th, issued Mar. 1971; title from cover.