28 research outputs found
Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naĂŻve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity
Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping
Peer reviewe
GAD65 An Immunomodulator in Type 1 Diabetes
Type 1 diabetes (T1D) is caused by a deficiency of insulin as a result of an autoimmune destruction of the pancreatic ÂČ -cells. A possibility to preserve remaining ÂČ -cells in children with newly diagnosed T1D is of great importance since sustained ÂČ -cell function is recognized to result in reduced end-organ complications. Glutamic acid decarboxylase 65 (GAD65) is one of the major antigens targeted by self-reactive T cells in T1D, and immunomodulation with GAD65 formulated in aluminum (GAD-alum) has been considered both in prevention and treatment of T1D. Results from a Phase II trial have shown clinical effect of subcutaneous injections with GAD-alum, this was unfortunately not fully confirmed in the following larger Phase III trial which therefore was closed after 15 months. The general aim of this thesis was to study the immunomodulatory effect of GAD-alum-treatment in children with T1D participating in the Phase II and Phase III trials. We hypothesized that treatment with GAD-alum contributes to the preservation of residual insulin secretion through deviation of the GAD65-specific immune response from a destructive to a protective process, accompanied by a shift from T helper (Th) 1 towards a predominant Th2 profile. In the Phase II trial, GAD-alum-treated patients responded with an early GAD65-specific Th2 skewed cytokine secretion, with highest IL-5 and IL-13 secretion in clinical responders. Also, the CCR4/CCR5 ratio indicating balance between Th2/Tc2 and Th1/Tc1 responses, increased in treated patients. The recall response to GAD65 was characterized by a wide range of cytokines, but the relative contribution of each cytokine suggests a shift towards a more pronounced Th2-associated profile over time. Induction of a CD4+ cell subset upon GAD65-stimulation 4 years after treatment, suggesting clonal expansion of the memory T-cell compartment upon antigen re-challenge, was seen in parallel to a persistent GAD65-specific cytokine response. Finally, even if the phase III trial failed to reach the primary endpoint at 15 months, a subgroup analysis showed that the treatment had an effect on preservation of residual insulin secretion, but the effect was not seen until after 30 months. Taken together, these results suggest that GAD-alum treatment might exert its effect through induction of an early Th2 skewed immune response which tends to deviate away from a destructive Th1/Tc1 response upon GAD65 re-challenge, and generation of GAD65-specific memory T cells that produce cytokines and exert effector responses which may be important for regulating GAD65 immunity. Continued research to better understand how immunomodulation with autoantigen modifies T-cell responses and also which patients are suitable for treatment, is crucial for optimizing future intervention trials using ÂČ -cell antigens
Grafisk Design för vĂ€lmĂ„ende i en digital vĂ€rld â En fenomenologisk undersökning och visuell retorisk analys av Headspace anvĂ€ndargrĂ€nssnitt och design
Headspace Àr en mindfulnessinriktad mobilapplikation som Àmnar att förbÀttra anvÀndarens vÀlmÄende. Denna uppsats syfte Àr att undersöka hur Headspace som mobilapplikation i sitt anvÀndargrÀnssnitt och visuella uttryck pÄverkar mottagaren. Detta kommer undersökas dels genom en litteraturstudie som tar upp begrepp som mindfulness, storytelling, ontologisk design och mÀnniska-maskin interaktion. Undersökningen genomförs med grund i visuell retorik och fenomenologi, dÀr den visuellt-retoriska delen fokuserar pÄ hur det visuella skapar mening och pÄverkar mottagaren medan den fenomenologiska delen fokuserar pÄ inviduella anvÀndares kÀnslor och upplevelser av mobilapplikationen. Slutsatsen Àr att genom att gestalta kÀnslor visar Headspace pÄ förstÄelse och empati gentemot anvÀndaren. De gör metoden minfulness till sin och skapar ett förtroende gentemot anvÀndaren genom att uppfattas vÀgledande och omhÀndertagande i sitt uttryck och genom sina handlingar
Grafisk Design för vĂ€lmĂ„ende i en digital vĂ€rld â En fenomenologisk undersökning och visuell retorisk analys av Headspace anvĂ€ndargrĂ€nssnitt och design
Headspace Àr en mindfulnessinriktad mobilapplikation som Àmnar att förbÀttra anvÀndarens vÀlmÄende. Denna uppsats syfte Àr att undersöka hur Headspace som mobilapplikation i sitt anvÀndargrÀnssnitt och visuella uttryck pÄverkar mottagaren. Detta kommer undersökas dels genom en litteraturstudie som tar upp begrepp som mindfulness, storytelling, ontologisk design och mÀnniska-maskin interaktion. Undersökningen genomförs med grund i visuell retorik och fenomenologi, dÀr den visuellt-retoriska delen fokuserar pÄ hur det visuella skapar mening och pÄverkar mottagaren medan den fenomenologiska delen fokuserar pÄ inviduella anvÀndares kÀnslor och upplevelser av mobilapplikationen. Slutsatsen Àr att genom att gestalta kÀnslor visar Headspace pÄ förstÄelse och empati gentemot anvÀndaren. De gör metoden minfulness till sin och skapar ett förtroende gentemot anvÀndaren genom att uppfattas vÀgledande och omhÀndertagande i sitt uttryck och genom sina handlingar
NÀr musiken talar - pÄ barnets nivÄ : En studie om musikens betydelse för barns sprÄkliga utveckling
 This is a study that wants to investigate whether music can contribute to linguistic development through interviews. In the literature review, researchers and educators clarify the connection between music and languages. The study is based on the sociocultural perspective. The six educators interviewed for the study suggest that music has a contributing effect on children's language development. Furthermore, it is explained that music brings joy and fellowship that becomes an interaction between the children in preschool. By interaction and learning of other people's previous experiences, the children can develop their language. In the discussion it appears that the music gathering for children gives a sense of safety, which makes them comfortable to express feelings and thoughts, which in turn leads them to communicate and interact with others to develop their language
E-handlarens digitala egenskaper och dess inverkan pÄ konsumentens subjektiva uppfattning : En kvantitativ studie om förtroende och misstro
The study examines how online retailers' digital characteristics affect consumers' perception of the online retailer and how the perception affects trust and distrust of the online retailer. The result aims to help online retailers gain an understanding of which characteristics are most salient and strategically important to generate trust among consumers. The digital properties that the study examines are, technical functionality, information quality, user-friendliness, graphic design, navigation, and recognition. A consumer's perception is considered either functional, or motivational. To investigate the relationship between the variables, a quantitative survey was carried out. Collected data was analyzed using statistical measures to investigate the purpose of the study. The internal reliability was calculated, the variables distrust, information quality, graphic design, recognition, and functional perception resulted in an acceptable internal reliability. Correlation analyzes were performed between the independent variables to rule out multicollinearity, then regression analyzes were performed to examine relationships between the variables. The correlation test resulted in exclusion of multicollinearity. The regression analysis resulted in graphic design and navigation being shown to have a significant positive impact on functional perception, which means that an appealing graphic design and an intuitive navigation on an online retailers' website contribute to the website being perceived as functioning well. Graphic design was the only variable that showed a significant positive impact on motivational perception. An attractive graphic design can thus motivate a consumer to choose a specific online retailer and to become a returning customer, furthermore, graphic design also seems to be important for creating a strong connection to the company. The regression analysis also showed that only motivational perception can explain trust and distrust with significance. In other words, a consumer's positive motivational perception can increase its trust and distrust of an e-merchant. The analysis resulted in a generally low degree of explanation, which indicates that there are variables, or dimensions of the investigated variables that the study ignored, that can explain trust and distrust. The factors may therefore be of interest to investigate in future studies.Studien undersoÌker hur e-handlares digitala egenskaper paÌverkar konsumenters uppfattning av e- handlaren samt hur uppfattningen paÌverkar foÌrtroendet och misstron foÌr e-handlaren. Resultatet straÌvar efter att hjaÌlpa e-handlare faÌ en foÌrstaÌelse foÌr vilka egenskaper som aÌr mest framtraÌdande och strategiskt viktiga foÌr att generera foÌrtroende bland konsumenter. De digitala egenskaper som studien undersoÌker aÌr, teknisk funktionalitet, informationskvalitet, anvaÌndarvaÌnlighet, grafisk design, navigation och igenkaÌnning. En konsuments uppfattning anses antingen vara funktionell, eller motiverande. FoÌr att undersoÌka relationen mellan variablerna genomfoÌrdes en kvantitativ enkaÌtundersoÌkning. Insamlad data analyserades med statistiska maÌtt foÌr att utreda studiens syfte. Den interna reliabiliteten beraÌknades, variablerna misstro, informationskvalitet, grafisk design, igenkaÌnning samt funktionell uppfattning resulterade i en acceptabel intern reliabilitet. Korrelationsanalyser utfoÌrdes mellan de oberoende variablerna foÌr att utesluta multikollinearitet, daÌrefter utfoÌrdes regressionsanalyser foÌr att undersoÌka samband mellan variablerna. Korrelationstestet resulterade i att multikollinearitet helt kunde uteslutas. Regressionsanalysen resulterade i att grafisk design och navigation kunde paÌvisas ha en signifikant positiv inverkan paÌ funktionell uppfattning, vilket betyder att en tilltalande grafisk design och en intuitiv navigering paÌ en e-handlares hemsida bidrar till att hemsidan upplevs som vaÌlfungerande. Grafisk design var den enda variabeln som visade en signifikant positiv inverkan paÌ motiverande uppfattning. En attraktiv grafisk design kan daÌrmed motivera en konsument att vaÌlja en specifik e-handlare och att bli en aÌterkommande kund, vidare verkar aÌven grafisk design vara viktigt foÌr att skapa en stark koppling till foÌretaget. Regressionsanalysen visade aÌven att endast motiverande uppfattning kan foÌrklara foÌrtroende och misstro med signifikans. Med andra ord kan en konsuments positiva motiverande uppfattning oÌka dess foÌrtroende och misstro foÌr en e-handlare. Analysen resulterade i en generellt laÌg foÌrklaringsgrad, vilket indikerar att det finns variabler, eller dimensioner av de undersoÌkta variablerna som studien bortsett, som kan foÌrklara foÌrtroende och misstro. Faktorerna kan daÌrfoÌr vara av intresse att undersoÌka i framtida studier
E-handlarens digitala egenskaper och dess inverkan pÄ konsumentens subjektiva uppfattning : En kvantitativ studie om förtroende och misstro
The study examines how online retailers' digital characteristics affect consumers' perception of the online retailer and how the perception affects trust and distrust of the online retailer. The result aims to help online retailers gain an understanding of which characteristics are most salient and strategically important to generate trust among consumers. The digital properties that the study examines are, technical functionality, information quality, user-friendliness, graphic design, navigation, and recognition. A consumer's perception is considered either functional, or motivational. To investigate the relationship between the variables, a quantitative survey was carried out. Collected data was analyzed using statistical measures to investigate the purpose of the study. The internal reliability was calculated, the variables distrust, information quality, graphic design, recognition, and functional perception resulted in an acceptable internal reliability. Correlation analyzes were performed between the independent variables to rule out multicollinearity, then regression analyzes were performed to examine relationships between the variables. The correlation test resulted in exclusion of multicollinearity. The regression analysis resulted in graphic design and navigation being shown to have a significant positive impact on functional perception, which means that an appealing graphic design and an intuitive navigation on an online retailers' website contribute to the website being perceived as functioning well. Graphic design was the only variable that showed a significant positive impact on motivational perception. An attractive graphic design can thus motivate a consumer to choose a specific online retailer and to become a returning customer, furthermore, graphic design also seems to be important for creating a strong connection to the company. The regression analysis also showed that only motivational perception can explain trust and distrust with significance. In other words, a consumer's positive motivational perception can increase its trust and distrust of an e-merchant. The analysis resulted in a generally low degree of explanation, which indicates that there are variables, or dimensions of the investigated variables that the study ignored, that can explain trust and distrust. The factors may therefore be of interest to investigate in future studies.Studien undersoÌker hur e-handlares digitala egenskaper paÌverkar konsumenters uppfattning av e- handlaren samt hur uppfattningen paÌverkar foÌrtroendet och misstron foÌr e-handlaren. Resultatet straÌvar efter att hjaÌlpa e-handlare faÌ en foÌrstaÌelse foÌr vilka egenskaper som aÌr mest framtraÌdande och strategiskt viktiga foÌr att generera foÌrtroende bland konsumenter. De digitala egenskaper som studien undersoÌker aÌr, teknisk funktionalitet, informationskvalitet, anvaÌndarvaÌnlighet, grafisk design, navigation och igenkaÌnning. En konsuments uppfattning anses antingen vara funktionell, eller motiverande. FoÌr att undersoÌka relationen mellan variablerna genomfoÌrdes en kvantitativ enkaÌtundersoÌkning. Insamlad data analyserades med statistiska maÌtt foÌr att utreda studiens syfte. Den interna reliabiliteten beraÌknades, variablerna misstro, informationskvalitet, grafisk design, igenkaÌnning samt funktionell uppfattning resulterade i en acceptabel intern reliabilitet. Korrelationsanalyser utfoÌrdes mellan de oberoende variablerna foÌr att utesluta multikollinearitet, daÌrefter utfoÌrdes regressionsanalyser foÌr att undersoÌka samband mellan variablerna. Korrelationstestet resulterade i att multikollinearitet helt kunde uteslutas. Regressionsanalysen resulterade i att grafisk design och navigation kunde paÌvisas ha en signifikant positiv inverkan paÌ funktionell uppfattning, vilket betyder att en tilltalande grafisk design och en intuitiv navigering paÌ en e-handlares hemsida bidrar till att hemsidan upplevs som vaÌlfungerande. Grafisk design var den enda variabeln som visade en signifikant positiv inverkan paÌ motiverande uppfattning. En attraktiv grafisk design kan daÌrmed motivera en konsument att vaÌlja en specifik e-handlare och att bli en aÌterkommande kund, vidare verkar aÌven grafisk design vara viktigt foÌr att skapa en stark koppling till foÌretaget. Regressionsanalysen visade aÌven att endast motiverande uppfattning kan foÌrklara foÌrtroende och misstro med signifikans. Med andra ord kan en konsuments positiva motiverande uppfattning oÌka dess foÌrtroende och misstro foÌr en e-handlare. Analysen resulterade i en generellt laÌg foÌrklaringsgrad, vilket indikerar att det finns variabler, eller dimensioner av de undersoÌkta variablerna som studien bortsett, som kan foÌrklara foÌrtroende och misstro. Faktorerna kan daÌrfoÌr vara av intresse att undersoÌka i framtida studier