| 1. |
|
|
| 2. |
- Berglund, David, et al.
(författare)
-
Screening of mortality in transplant patients using an assay for immune function
- 2011
-
Ingår i: Transplant Immunology. - : Elsevier BV. - 0966-3274 .- 1878-5492. ; 24:4, s. 246-250
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: So far, the ImmuKnow Immune Cell Function Assay (Cylex, Inc., Columbia, MD, USA) has been used to assess risks of infection and rejection in transplant patients. We hypothesized that the ImmuKnow assay might be used for mortality screening in transplant patients overall. METHODS: In the period of February 2007 to December 2009, at the Uppsala University Hospital, 362 patients who received either kidney, kidney+pancreas, kidney+islet cells, liver or liver+kidney allografts were randomly screened using the ImmuKnow assay. All causes of mortality were compared between two groups: patients with at least one ImmuKnow assay below 175ng/mL and patients with all ImmuKnow assays from 175ng/mL and above. Subsequently, the frequency of rejection within thirty days of the ImmuKnow assay was compared between these two groups. RESULTS: The study included 1031 ImmuKnow assays obtained from the 362 patients. A total of 111 patients had at least one ImmuKnow below 175ng/mL and 251 patients had all their ImmuKnow assays from 175ng/mL and above. By January 31st 2010, 16 of 111 patients (14.4%) with at least one ImmuKnow assay below 175ng/mL were deceased, compared to 13 of 251 patients (5.2%) with all ImmuKnow assays from 175ng/mL and above (p=0.0053, Fisher's exact test). There was no difference in the frequency of rejection between the two groups (19.8% versus 17.5%, p=0.66). CONCLUSIONS: In addition to assessing relative risks of infection and rejection in transplant patients, the ImmuKnow assay may be used to identify patients with increased risk of short-term mortality. Transplant patients being highly overimmunosuppressed as assessed by the ImmuKnow assay do not seem to have a lower risk of short-term rejection.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Almroth, Andreas, et al.
(författare)
-
Further development of SAMPERS and modeling of urban congestion
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The need to more precisely represent the consequences of congestion mitigation policies in urban transport systems calls for replacement of the static equilibrium assignment by DTA in the integrated travel demand and traffic assignment models. Despite of the availability of DTA models and despite of the conceptual clarity of how such integration should take place, only few operational model systems have been developed for large-scale applications. We report on replacement of the static traffic assignment by two different DTAs in the four stage demand model for the Greater Stockholm region: the macroscopic analytic Visum DUE and microscopic simulation Transmodeler. First results show that even without systematic calibration the DTA is in reasonable agreement with observed traffic counts and travel times. The presented experiments did not reveal striking difference between using macroscopic and microscopic assignment package. However, given the clear trend to microscopic modeling and simulation on the travel demand side, the use of micro-simulation-based DTA package appears more natural from system integration perspective.
|
|
| 6. |
- Bejerot, Susanne, 1955-, et al.
(författare)
-
The Brief Obsessive-Compulsive Scale (BOCS) : a self-report scale for OCD and obsessive-compulsive related disorders
- 2014
-
Ingår i: Nordic Journal of Psychiatry. - : Informa Healthcare. - 0803-9488 .- 1502-4725. ; 68:8, s. 549-559
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date.Aim: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population.Method: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS.Results: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's alpha = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha = 0.94).Conclusions: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry.
|
|
| 7. |
- Berglund, Anders, et al.
(författare)
-
Social inequalities in non-small cell lung cancer management and survival : a population-based study in central Sweden
- 2010
-
Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 65:4, s. 327-333
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To examine possible associations between socioeconomic status, management and survival of patients with non-small cell lung cancer (NSCLC). Methods In a population-based cohort study, information was retrieved from the Regional Lung Cancer Register in central Sweden, the Cause of Death Register and a social database. ORs and HRs were compared to assess associations between educational level and management and survival. Results 3370 eligible patients with an NSCLC diagnosis between 1996 and 2004 were identified. There were no differences in stage at diagnosis between educational groups. A higher diagnostic intensity was observed in patients with high compared with low education. There were also social gradients in time between referral and diagnosis in early stage disease ( median time: low, 32 days; high, 17 days). Social differences in treatment remained following adjustment for prognostic factors ( surgery in early stage disease, high vs low OR 2.84; CI 1.40 to 5.79). Following adjustment for prognostic factors and treatment, the risk of death in early stage disease was lower in women with a high education ( high vs low HR 0.33; CI 0.14 to 0.77). Conclusion The results of this study indicate that socioeconomically disadvantaged groups with NSCLC receive less intensive care. Low education remained an independent predictor of poor survival only in women with early stage disease. The exact underlying mechanisms of these social inequalities are unknown, but differences in access to care, co-morbidity and lifestyle factors may all contribute.
|
|
| 8. |
- Berglund, David, et al.
(författare)
-
Isolation, expansion and functional assessment of CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients awaiting kidney transplantation
- 2012
-
Ingår i: Transplant Immunology. - : Elsevier BV. - 0966-3274 .- 1878-5492. ; 26:1, s. 27-33
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The immunosuppressive properties of regulatory T cells have emerged as an attractive tool for the development of immunotherapies in various disease contexts, e.g. to treat transplantation induced immune reactions. This paper focuses on the process of obtaining and functionally characterizing CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients awaiting kidney transplantation. Methods: From October 2010 to March 2011 uremic patients awaiting living donor kidney transplantation, and their corresponding kidney donors, were enrolled in the study. A total of seven pairs were included. Isolation of CD4+CD25+FoxP3+ regulatory T cells was performed by magnetic activated cell sorting of peripheral blood mononuclear cells obtained from the uremic patients. Donor specific Tr1 cells were differentiated by repetitive stimulation of immature CD4+ T cells with immature dendritic cells, with the T cells coming from the future kidney recipients and the dendritic cells from the corresponding kidney donors. Cells were then expanded and functionally characterized by the one-way mixed leukocyte reaction and assessment of IL-10 production. Phenotypic analysis was performed by flow cytometry. Results: The fraction of CD4+CD25+FoxP3+ regulatory T cells after expansion varied from 39.1 to 50.4% and the cells retained their ability to substantially suppress the mixed leukocyte reaction in all but one patient (3.8–19.2% of the baseline stimulated leukocyte activity, p<0.05). Tr1 cells were successfully differentiated from all but one patient and produced high levels of IL-10 when stimulated with immature dendritic cells (1,275–11,038% of the baseline IL-10 secretion, pb0.05). Conclusion: It is practically feasible to obtain and subsequently expand CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients without loss of function as assessed by in vitro analyses. This forms a base for adoptive regulatory T cell therapy in the setting of living donor kidney transplantation.
|
|
| 9. |
- Berglund, David, et al.
(författare)
-
Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials
- 2013
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 173:2, s. 310-322
-
Tidskriftsartikel (refereegranskat)abstract
- Adoptive transfer of regulatory T cells (Tregs) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with Treg therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4+CD25highCD127low Tregs from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare Treg preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded Treg preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that Treg preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the Treg preparations. In particular, FACS-sorted Treg preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted Treg preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with Tregs from uraemic patients that may guide future efforts to produce clinical-grade Tregs for use in kidney transplantation.
|
|
| 10. |
- Berglund, David, 1984-
(författare)
-
Preparatory Studies to Introduce Regulatory T Cells in Clinical Transplantation
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Solid organ transplantation has evolved from being an experimental procedure to a life-saving treatment for patients with end-stage organ failure. The risk of losing a transplant due to acute rejection is very low with the use of modern immunosuppressive protocols and the short-term results are impressive. However, long-term outcomes are suboptimal and transplant recipients are at increased risks for severe complications such as cancers, opportunistic infections and cardiovascular events. The previous struggle to achieve short-term survival has turned into a search for new strategies to improve patient and transplant longevity.Regulatory T cells (TRegs), a subset of T cells, occur naturally in the immune system and have the capacity to down regulate immune responses. Under normal conditions they maintain self-tolerance and prevent excessive immune activation. Functional TReg defects lead to a massive autoimmune response and are not compatible with life. Preclinical data support that TRegs can be used as a cell therapy to prevent transplant rejection, with the potential to minimize the need for traditional immunosuppression and improve the long-term outcome.This thesis aims to enhance the translation of TReg cell therapy to clinical organ transplantation. In particular, strategies for isolation and expansion of TRegs from uremic patients awaiting kidney transplantation have been assessed. A non-invasive imaging technique to study T cell products after intravenous administration was developed, for use in future clinical trials. The performance of a novel cell purification technique was investigated to potentially improve the clinical production of TRegs.The thesis demonstrates that TRegs can be isolated and expanded from uremic patients to display potent suppressive properties in vitro. The mode of isolation and expansion affect the functional characteristics, where cells purified with cytometry based techniques and expanded with mature dendritic cells were the most advantageous. T cells can be labeled using the radioactive tracer [111In]oxine with preserved viability and subsequently followed in vivo with SPECT/CT for more than 1 week after intravenous administration. The use of microfluidic switch technology offers a novel way of purifying TRegs at high speed, purity and viability, under conditions compatible with clinical use.
|
|
