Immune response to insulin and changes in the gut immune system in children with or at risk for type 1 diabetes

Type 1 diabetes (T1D) is considered to be an autoimmune disease. The cause of T1D is the destruction of insulin-producing β-cells in the pancreatic islets. The autoimmune nature of T1D is characterized by the presence of autoreactive T-cells and autoantibodies against β-cell molecules. Insulin is the only β-cell-specific autoantigen associated with T1D but the insulin autoantibodies (IAAs) are difficult to measure with proper sensitivity. T-cell assays for detection of autoreactive T-cells, such as insulin-specific T-cells, have also proven to be difficult to perform. The genetic risk of T1D is associated with the HLA gene region but the environmental factors also play an important role. The most studied environmental risk factors of T1D are enteroviruses and cow's milk which both affect the immune system through the gut. One hypothesis is that the insulin-specific immune response develops against bovine insulin in cow's milk during early infancy and later spreads to include human insulin. The aims of this study were to determine whether the separation of immunoglobulin (Ig)G from plasma would improve the sensitivity of the IAA assay and how insulin treatment affects the cellular immune response to insulin in newly diagnosed patients. Furthermore, the effect of insulin concentration in mother's breast milk on the development of antibodies to dietary insulin in the child was examined. Small intestinal biopsies were also obtained from children with T1D to characterize any immunological changes associated with T1D in the gut. The isolation of the IgG fraction from the plasma of T1D patients negative for plasma IAA led to detectable IAA levels that exceeded those in the control children. Thus the isolation of IgG may improve the sensitivity of the IAA assay. The effect of insulin treatment on insulin-specific T-cells was studied by culturing peripheral blood mononuclear cells with insulin. The insulin stimulation induced increased expression of regulatory T-cell markers, such as Foxp3, in those patients treated with insulin than in patients examined before initiating insulin treatment. This finding suggests that insulin treatment in patients with T1D stimulates regulatory T-cells in vivo and this may partly explain the difficulties in measuring autoantigen-specific T-cell responses in recently diagnosed patients. The stimulation of regulatory T-cells by insulin treatment may also explain the remission period often seen after initiating insulin treatment. In the third study we showed that insulin concentration in mother's breast milk correlates inversely with the levels of bovine insulin-specific antibodies in those infants who were exposed to cow's milk proteins in their diet, suggesting that human insulin in breast milk induces tolerance to dietary bovine insulin. However, in infants who later developed T1D-associated autoantibodies, the insulin concentration in their mother's breast milk was increased. This finding may indicate that in those children prone to β-cell autoimmunity, breast milk insulin does not promote tolerance to insulin. In the small intestinal biopsies the presence of several immunological markers were quantified with the RT-PCR. From these markers the expression of the interleukin (IL)-18 cytokine was significantly increased in the gut in patients with T1D compared with children with celiac disease or control children. The increased IL-18 expression lends further support for the hypothesis that the gut immune system is involved in the pathogenesis of T1D.

Methodological perspectives for register-based health system performance assessment : Developing a hip fracture monitoring system in Finland

The resources of health systems are limited. There is a need for information concerning the performance of the health system for the purposes of decision-making. This study is about utilization of administrative registers in the context of health system performance evaluation. In order to address this issue, a multidisciplinary methodological framework for register-based data analysis is defined. Because the fixed structure of register-based data indirectly determines constraints on the theoretical constructs, it is essential to elaborate the whole analytic process with respect to the data. The fundamental methodological concepts and theories are synthesized into a data sensitive approach which helps to understand and overcome the problems that are likely to be encountered during a register-based data analyzing process. A pragmatically useful health system performance monitoring should produce valid information about the volume of the problems, about the use of services and about the effectiveness of provided services. A conceptual model for hip fracture performance assessment is constructed and the validity of Finnish registers as a data source for the purposes of performance assessment of hip fracture treatment is confirmed. Solutions to several pragmatic problems related to the development of a register-based hip fracture incidence surveillance system are proposed. The monitoring of effectiveness of treatment is shown to be possible in terms of care episodes. Finally, an example on the justification of a more detailed performance indicator to be used in the profiling of providers is given. In conclusion, it is possible to produce useful and valid information on health system performance by using Finnish register-based data. However, that seems to be far more complicated than is typically assumed. The perspectives given in this study introduce a necessary basis for further work and help in the routine implementation of a hip fracture monitoring system in Finland.

The watershed simulation and forecasting system in the National Board of and the Environment

Yhteenveto: Vesistömalleihin perustuva vesistöjen seuranta- ja ennustejärjestelmä vesi- ja ympäristöhallinnossa

Private and municipal forests and the forestry planning system in Japan - trends and problems after World War II.

XVIII IUFRO World Congress, Ljubljana 1986.

Requirements for information management system in agricultural contracting

Menneinä vuosikymmeninä maatalouden työt ovat ensin koneellistuneet voimakkaasti ja sittemmin mukaan on tullut automaatio. Nykyään koneiden kokoa suurentamalla ei enää saada tuottavuutta nostettua merkittävästi, vaan työn tehostaminen täytyy tehdä olemassa olevien resurssien käyttöä tehostamalla. Tässä työssä tarkastelun kohteena on ajosilppuriketju nurmisäilörehun korjuussa. Säilörehun korjuun intensiivisyys ja koneyksiköiden runsas määrä ovat työnjohdon kannalta vaativa yhdistelmä. Työn tavoitteena oli selvittää vaatimuksia maatalouden urakoinnin tueksi kehitettävälle tiedonhallintajärjestelmälle. Tutkimusta varten haastateltiin yhteensä 12 urakoitsijaa tai yhteistyötä tekevää viljelijää. Tutkimuksen perusteella urakoitsijoilla on tarvetta tietojärjestelmille.Luonnollisesti urakoinnin laajuus ja järjestelyt vaikuttavat asiaan. Tutkimuksen perusteella keskeisimpiä vaatimuksia tiedonhallinnalle ovat: • mahdollisimman laaja, yksityiskohtainen ja automaattinen tiedon keruu tehtävästä työstä • karttapohjaisuus, kuljettajien opastus kohteisiin • asiakasrekisteri, työn tilaus sähköisesti • tarjouspyyntöpohjat, hintalaskurit • luotettavuus, tiedon säilyvyys • sovellettavuus monenlaisiin töihin • yhteensopivuus muiden järjestelmien kanssa Kehitettävän järjestelmän tulisi siis tutkimuksen perusteella sisältää seuraavia osia: helppokäyttöinen suunnittelu/asiakasrekisterityökalu, toimintoja koneiden seurantaan, opastukseen ja johtamiseen, työnaikainen tiedonkeruu sekä kerätyn tiedon käsittelytoimintoja. Kaikki käyttäjät eivät kuitenkaan tarvitse kaikkia toimintoja, joten urakoitsijan on voitava valita tarvitsemansa osat ja mahdollisesti lisätä toimintoja myöhemmin. Tiukoissa taloudellisissa ja ajallisissa raameissa toimivat urakoitsijat ovat vaativia asiakkaita, joiden käyttämän tekniikan tulee olla toimivaa ja luotettavaa. Toisaalta inhimillisiä virheitä sattuu kokeneillekin, joten hyvällä tietojärjestelmällä työstä tulee helpompaa ja tehokkaampaa.