| 1. |
|
|
| 2. |
- Andersson, Johanna, et al.
(author)
-
Actor or arena : Contrasting translations of a law on interorganizational integration
- 2012
-
In: Journal of Health Organization & Management. - : Emerald Group Publishing Limited. - 1477-7266 .- 1758-7247. ; 26:6, s. 778-793
-
Journal article (peer-reviewed)abstract
- Purpose – A Swedish framework law has enabled integration between public agencies in vocational rehabilitation. With the support of this law, coordination associations can be formed to fund and organize joint activities. The purpose of this study is to describe and analyze how the law has been interpreted and translated into local coordination associations and how local institutional logics have developed to guide the organization of these associations. Design/methodology/approach – Data was collected through observations of meetings within two coordination associations and supplemented with documents. The material was analyzed by compilation and examination of data from field notes, whereupon the most important aspects were crystallized and framed with institutional organization theory. Findings – Two different translations of the law were seen in the associations studied: the association as an independent actor, and as an arena for its member organizations. Two subsequent institutional logics have developed, influencing decisions on autonomy, objectives and rationality for initiating and organizing in the two associations and their activities. The institutional logics are circular, further enhancing the different translations creating different forms of integration. Research implications/limitations – Both forms of integration are legitimate, but the different translations have created integration with different degrees of autonomy in relation to the member organizations. Only a long-term analysis can show whether one form of integration is more functional than the other. Originality/value – This article is based on an extensive material providing insights into a form of interorganizational integration which has been scarcely researched. The findings show how different translations can influence the integration of welfare services.
|
|
| 3. |
- Axelsson, Stina, et al.
(author)
-
Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial
- 2013
-
In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3418-3424
-
Journal article (peer-reviewed)abstract
- OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.
|
|
| 4. |
- Axelsson, Stina, et al.
(author)
-
Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
- 2011
-
In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:12
-
Journal article (peer-reviewed)abstract
- 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 GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) 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 GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-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 GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.
|
|
| 5. |
- Axelsson, Stina, et al.
(author)
-
Preserved C-peptide 30 months after GAD-alum treatment of children and adolescents with recent-onset type 1 diabetes, and its relation to immune markers
-
Other publication (other academic/artistic)abstract
- Glutamic acid decarboxylase 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes (T1D). Although alum-formulated GAD65 (GAD-alum) induced preservation of residual insulin secretion in a previous clinical Phase II trial, recent Phase II and Phase III trials failed to reach their primary end-points. The European Phase III trial was therefore closed after 15 months, and the 30 months follow-up period was completed only for a minority of the patients. This study aimed to assess whether GAD-alum preserved β-cell function in those recent-onset T1D patients who completed their 30 months visit in the European Phase III trial, and to characterize their GAD65-induced cytokine secretion and proliferation. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and after 1, 3, 9, 15 and 21 months from the 148 Swedish subjects included in the Phase III GAD-alum trial, and also at 30 months from 45 patients who had reached the final visit before the trial was closed. Patients had been randomly assigned into three arms: 4 doses of GAD-alum (4D), 2 doses of GAD-alum followed by two doses of placebo (2D), or 4 doses of placebo. Cytokine secretion was detected in cell culture supernatants by Luminex, after 7 days of in vitro culture. Cell proliferation was determined by 3H thymidine incorporation assay. Fasting and stimulated C-peptide was analysed in serum. Patients treated with 2 doses of GAD-alum had less decline of both fasting (p=0.040) and stimulated C-peptide (p=0.012) after 30 months, and a larger proportion of these patients preserved >25% of their initial stimulated C-peptide AUC compared to placebo (p=0.012). Both 2D and 4D patients showed increased PBMC proliferation to GAD65 and a cytokine profile that tended to switch towards a more predominant Th2 associated profile over time. The results support the concept of GAD-alum treatment, but no specific immune markers have been identified.
|
|
| 6. |
- Axelsson, Ulrik, et al.
(author)
-
Strukturerad miljödatahantering inom järn- och stålindustri. Etapp 2; Miljöinformationssystem
- 2004
-
Reports (other academic/artistic)abstract
- Det analysarbete som gjorts har i denna etapp har genomförts i samarbete med samma tre typföretag - Höganäs AB, Sandvik Materials Technology samt Ovako Steel AB - som i etapp 1. De tre företagen hanterar vardera en avsevärda mängd miljödata som idag finns utspridd inom organisationerna och lagras i olika system varför sammanställningar försvåras. Det betyder att den miljödata som mäts och beräknas lagras på ett sätt som innebär en irrationell hantering av den samlade miljöinformationen. Den analys som visar att det inom järn- och stålbranschen går att beskriva verksamhetsprocesser på ett enhetligt sätt och att miljödatan som företagen mäter, beräknar och lagrar överensstämmer i mycket stor grad. Baserat på detta har en branschgemensam miljödatastruktur varit möjlig att ta fram. Denna struktur är framtagen för att kunna lagra miljödata för utsläpp till luft, utsläpp till vatten, energianvändning och avfall. Utifrån den miljödatastruktur som arbetats fram och genom diskussioner med representanter för typföretagen i projektet har en översiktlig systemskiss för ett miljöinformationssystem inom järn- och stålindustrin tagits fram. Detta miljöinformationssystem kan vara generellt inom branschen och svara upp mot gemensamma krav på hantering av miljödata.
|
|
| 7. |
|
|
| 8. |
- Chéramy, Mikael, et al.
(author)
-
GAD65 autoantibody (GADA) responses in Type 1 diabetes patients participating in a phase III GAD-alum intervention trial
-
Other publication (other academic/artistic)abstract
- Glutamic acid decarboxylase 65 kDa isoform (GAD65) is a major autoantigen in type 1 diabetes (T1D). Although aluminum-formulated GAD65 (GAD-alum) induced preservation of residual insulin secretion in a previous clinical phase II trial, recent phase II and III trials failed to reach their primary end-points. The European phase III trial was therefore closed after 15 months, and the entire study period was completed only for a minority of the patients. This study aimed to characterize GAD65 autoantibodies (GADA) and Tyrosine phosphatase IA-2 autoantibody (IA-2A) levels, GADA IgG1-4 subclass distribution, B-cell frequencies/phenotypes and cytokine secretion. We also assessed whether GAD-alum preserved β-cell function in the small subgroup of Swedish patients who completed the 30 months visit. Serum samples and peripheral blood mononuclear cells (PBMC) were collected at baseline and after 1, 3, 9, 15 and 21 months from the 148 Swedish subjects included in the trial, and also at 30 months from the 45 patients who reached the final visit. Patients were randomly assigned to; i) 4 doses of GAD-alum (4D), ii) 2 doses of GAD-alum followed by two doses of placebo (2D), or iii) 4 doses of placebo.GADA titers were induced both in the 4D and 2D group compared to placebo, and 4D patients also displayed a higher GADA fold-change after receiving the two additional injections compared to the 2D group. The 4D group switched to a higher frequency of GADA IgG4, associated to a Th2 type response at 9 months, whereas an association between GADA fold-change and GAD65-induced in vitro cytokine secretion was observed in the 2D group. These findings suggest that the humoral response, induced by the 2D treatment, seems to be associated with a GAD65-specific cellular response, while 4D induces a distinct humoral response. Even though GADA titers were elevated, no changes in B-cell frequencies or phenotype were observed in any group. IA-2A levels declined at a similar rate in all groups during the trial.The subgroup of patients who completed the 30 month visit receiving 2 doses of GAD-alum had less decline of both fasting and stimulated C-peptide after 30 months compared to placebo. These results support the concept of GAD-alum treatment, but no specific immune markers have been identified.
|
|
| 9. |
- Ludvigsson, Johnny, et al.
(author)
-
Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
- 2011
-
In: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
|
|
| 10. |
- Ludvigsson, Johnny, 1943-, et al.
(author)
-
GAD treatment and insulin secretion in recent-onset type 1 diabetes
- 2008
-
In: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
-
Journal article (peer-reviewed)abstract
- Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
|
|
