| 1. |
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| 2. |
- Andersson, Lisa, et al.
(författare)
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Implementering av innovativa systemlösningar för hållbar dagvattenhantering
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Projektet Klimatsäkrade systemlösningar för urbana ytor syftar till att stärka städers förmåga att hantera ökad urbanisering och förändrat klimat, bland annat genom att utveckla innovativa systemlösningar för dagvattenhantering. I detta delprojekt har hinder och utmaningar för implementering av innovativa systemlösningar i stadsutvecklingsprocesser identifierats genom intervjuer med sakkunniga teknikexperter samt tjänstepersoner från olika förvaltningar. Som komplement har Svenskt Vattens publikationer P105 (Svenskt Vatten, 2011) och P110 (Svenskt Vatten, 2016) som är branschstandard för dagvattenhantering, samt utvalda kommuners policydokument analyserats för att undersöka hur dessa förhåller sig till innovativa systemlösningar för dagvattenhantering. Teoretisk utgångspunkt har varit studier kring vad som påverkar utveckling och spridning av tekniska innovationssystem (Bergek, 2008; Hellsmark, Bergek, Hellström, & Malmquist, 2014) samt teorier om innovation i offentlig sektor (Mulgan, 2007; Mulgan, 2014; Nählinder, 2013; Nählinder & Fogelberg Eriksson, 2017). De främsta faktorer som har identifierats påverka implementering av systemlösningar för dagvattenhantering är innovationskultur, samverkan vid planering, kunskap och ekonomi. För att överbrygga dessa hinder har rekommendationer för hållbar dagvattenhantering och uppdaterade riktlinjer för utformning av dagvattenstrategi utvecklats. För att underlätta samverkan samt val av dagvattenlösning har även ett beslutsstöd utvecklats för att kunna användas i ett tidigt skede vid planering (Brisvåg, 2017).
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| 3. |
- Caballero-Corbalán, José, et al.
(författare)
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Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation
- 2012
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 175:1, s. 163-168
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Tidskriftsartikel (refereegranskat)abstract
- Background. Histidine-tryptophan-ketoglutarate (HTK) has been established as an alternative to University-of-Wisconsin solution (UWS) for abdominal organ preservation, but data about HTK efficiency to preserve pancreata during prolonged cold ischemia time (CIT) are conflicting. In human islet transplantation, HTK provided similar isolation outcomes after short CIT. The present study aimed to investigate whether islets can be successfully isolated from HTK-preserved pancreata after prolonged CIT compared with UWS. Materials and Methods. Sixty-four human pancreata retrieved from donors meeting criteria for kidney donation were perfused utilizing either HTK or UWS and preserved for more or less than 10 h prior to islet isolation. Along with parameters related to isolation and islet quality assessment, the dry-to-wet weight ratio was evaluated. Results. Donor-and procurement-related factors did not vary between HTK- and UWS-perfused pancreata. The dry-to-wet weight ratio was lower in HTK-preserved pancreata indicated tissue edema (21.0% +/- 3.5% versus 24.8% +/- 2.0%, P = 0.007). Isolation-related variables differed between experimental groups after prolonged CIT with respect to purified packed tissue volume (9.1 +/- 5.0 versus 17.2 +/- 8.1 mu L/g, P = 0.004) and islet yield (1910 +/- 980 versus 3150 +/- 1420 IE/g, P = 0.012). Islet purity and survival after culture were similar after HTK or UWS perfusion. The preservation solution did not affect in vitro function and transplantability of isolated islets. Conclusions. Compared with UWS, HTK has similar efficiency to preserve human pancreata for subsequent islet isolation during <10 h CIT but seems to be limited for prolonged cold storage. (C) 2012 Elsevier Inc. All rights reserved.
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| 4. |
- Dacasa, Hugo, et al.
(författare)
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Single-shot extreme-ultraviolet wavefront measurements of high-order harmonics
- 2019
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Ingår i: Optics Express. - 1094-4087. ; 27:3, s. 2656-2670
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Tidskriftsartikel (refereegranskat)abstract
- We perform wavefront measurements of high-order harmonics using an extreme-ultraviolet (XUV) Hartmann sensor and study how their spatial properties vary with different generation parameters, such as pressure in the nonlinear medium, fundamental pulse energy and duration as well as beam size. In some conditions, excellent wavefront quality (up to 휆/11) was obtained. The high throughput of the intense XUV beamline at the Lund Laser Centre allows us to perform single-shot measurements of both the full harmonic beam generated in argon and individual harmonics selected by multilayer mirrors. We theoretically analyze the relationship between the spatial properties of the fundamental and those of the generated high-order harmonics, thus gaining insight into the fundamental mechanisms involved in high-order harmonic generation (HHG).
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| 5. |
- Ejhed, Helene, et al.
(författare)
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Nettobelastning av metaller i Dalälven
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Belastning och utsläpp av metaller till vatten rapporteras inom ett flertal internat-ionella rapporteringar; årligen till HELCOM och OSPAR samt vart tredje år till EEA WISE SoE Emissions. Cd, Pb, Hg och Ni ingår i listan av prioriterade ämnen enligt dotterdirektivet (2008/105/EG) till EUs ramdirektiv för vatten (2000/60/EG). För att analysera utsläpp och transport av metaller till inlandsvatten och havet måste källorna, men även avskiljning (retentionen) från källan till havet beräknas. En av de viktigaste indataparametrarna för att beräkna retention av metallerna är partikulär andel av metallerna i vatten.Syftet med detta projekt var att beräkna retention av metaller under transport från källan till havet i ett helt huvudavrinningsområde, Dalälven. Syftet var vidare att ta fram bättre regressionsekvationer som kan skatta andel partikulär metall med ytter-ligare styrande data utöver de kemiska parametrar som användes i tidigare studier och som kan ta hänsyn till förutsättningarna i Dalälvens avrinningsområde. Detta arbete bygger vidare på en tidigare testad retentionsmodell och framtagna regress-ionsekvationer för partikulär andel metaller (Lindström och Håkanson 2001, Ejhed m.fl.2011) och bruttobelastning (utsläpp vid källan) av metaller beräknat för avrin-ningsområden i hela Sverige (Ejhed m.fl., 2010). De metaller som hanterades i projektet var de prioriterade ämnena Cd, Hg, Pb och Ni, samt Cu och Zn som prio-riterades av Naturvårdsverket.För att förbättra regressionsekvationer för beräkning av andel partikulära metaller och anpassa till Dalälvens avrinningsområde utökades den befintliga miljööver-vakningen i Dalälven genom detta projekt med provtagning och analys av metaller i ofiltrerade prover både vid de redan befintliga provplatserna och vid ytterligare fem provplatser, i samråd med länsstyrelsen i Dalarna. Både flödesdata, andra ke-midata och markanvändning studerades för att bestämma vilka faktorer som styr andel metaller i partikulär form. Ekvationer togs fram för beräkning av andel me-taller i löst form för alla ovan nämnda metaller. Tillsammans med totalhalterna kan andel metaller i partikulär form skattas för alla metallerna i alla områden.Av analysen framgår att det finns stora skillnader för partikulär respektive löst andel för de olika metallerna och de olika områdena. Den största källan till variat-ion är dock pH. I sura vatten så som Lill-Fämtan är nästan alla metaller i löst form medan i mer alkaliska områden så som Dalälven Älvkarleby finns mycket större andel metaller i partikulär form. Vatten med större tillrinningsområden har oftast högre pH värden eftersom bidragen av välbuffrat grundvatten är större. Detta gäller också för sjöar med längre uppehållstider. Områden med stor andel åkermark och låg terräng uppvisar också högre andel metaller i partikulär form (Holen). Detta härrör förmodligen av mobilisering av större andel partiklar än i de andra vatten-dragen. Regressionerna som framtogs i denna rapport verka vara någorlunda uni-versella för alla studerade områden och påverkas inte av markanvändning eller om områdena är påverkade. Andel partikulära metaller varierar från 12% för Cu till 92% för Hg.En förenklad retentionsmodell utvecklades baserat på sjöarea, medeldjup, medel-tillrinning, partikulär andel metaller och fallhastighet för metallerna i Dalälvens avrinningsområde. Nettobelastningen och transport mellan delavrinningsområdena i Dalälven ner till havet beräknades genom att använda uppsättningen av HYPE-modellen baserat på Svenskt vattenarkiv 2010_2. Retentionsmodellens tillförlitlig-het testades genom att jämföra beräknad retention med motsvarande uppmätta värden i tre sjöar i Dalälvens avrinningsområde. Det konstaterades att den förenk-lade modellansatsen tämligen väl beskriver retentionen för de undersökta metaller-na. Den största avvikelsen noteras för Cu där den genomsnittliga retentionen un-derskattas med 16 procentenheter medan det för Zn och Pb skiljer 8 procentenheter mellan empiriskt och modellerat värde. Den sammanlagda retentionen för metal-lerna till havet varierar från 35% för Cu till 78% för Hg. Den inbördes skillnaden mellan olika metaller beror av deras varierande partikelbundna förekomst.Detta projekt har tagit fram en generell modell som med fördel skulle kunna appli-ceras och testas på andra avrinningsområden. Modellen kräver inte särskilt mycket indata, vilket kan anses vara en fördel då mycket indata sällan finns att tillgå i hu-vuddelen av Sveriges avrinningsområden. Modellen ger beräknad nettobelastning av källor till metaller och transport genom avrinningsområden, vilket är aktuellt och efterfrågat för påverkansanalys enligt ramdirektivet för vatten.Modellresultaten visar att beräkningar av retention och nettobelastning är ett nyttigt verktyg för att verifiera resultat av bruttobelastning och redovisning av källor till belastning. Det blev tydligt att det saknas källor i beräkningen av bruttobelastning-en i Dalälvens avrinningsområde. Det troliga är att läckage från gamla gruvdepo-nier saknas, men även att lokala variationer med högre läckage från diffusa källor kan orsaka skillnaden i uppmätt flodtransport och beräknad belastning.
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| 6. |
- Friberg, Andrew S, et al.
(författare)
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Transplantable functional islet mass – predictive biomarkers of graft function in islet after kidney transplanted patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal. Analysis of donor, islet isolation, quality control and recipient variables was undertaken in 110 islet after kidney (IAK) transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio (ΔCP/GCr). Using backward multiple regression the variables positively associated to ΔCP/GCr were islet volume transplanted (p<0.001) and glucose stimulated insulin secretion (SI) (p=0.009). Factors negatively associated to ΔCP/GCr were cold ischemia time (CIT) (p=0.002) and total tissue volume (p=0.009). Donor age, donor body mass index, number of retrieved organs from the donor, preservation solution, islet insulin content, body weight of the recipient of the islets had no influence on transplant function. The transplantable functional islet mass (TFIM), accounting for islet volume transplanted, SI, CIT, and total tissue volume explained 39% of the variance of the clinical outcome in the IAK data set. Therefore, the TFIM provides a straightforward and potent tool to guide the decision to utilize a specific islet preparation for clinical transplantation.
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| 7. |
- Friberg, Andrew S., et al.
(författare)
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Transplanted functional islet mass : donor islet preparation, and recipitent factors influence early graft function in islet-after-kidney patients
- 2012
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 93:6, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background.The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal.Methods. Analysis of 10 donor, 7 islet isolation, 3 quality control, and 6 recipient variables was undertaken in 110 islet-after-kidney transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio ([DELTA]CP/GCr).Results.Univariate analysis yielded islet volume transplanted (Spearman r=0.360, P<0.001) and increment of insulin secretion (r=0.377, P<0.001) as variables positively associated to [DELTA]CP/GCr. A negative association to [DELTA]CP/GCr was cold ischemia time (r=-0.330, P<0.001). A linear, backward-selection multiple regression was used to obtain a model for the transplanted functional islet mass (TFIM). The TFIM model, composed of islet volume transplanted, increment of insulin secretion, cold ischemia time, and exocrine tissue volume transplanted, accounted for 43% of the variance of the clinical outcome in the islet-after-kidney data set.Conclusion.The TFIM provides a straightforward and potent tool to guide the decision to use a specific islet preparation for clinical transplantation.
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| 8. |
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| 9. |
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| 10. |
- Holmgren, Madelene, et al.
(författare)
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Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.
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| 11. |
- Holmgren, Madelene, et al.
(författare)
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Prediction of cerebral perfusion pressure during carotid surgery : A computational fluid dynamics approach
- 2022
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Ingår i: Clinical Biomechanics. - : Elsevier BV. - 0268-0033 .- 1879-1271. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy.Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy.Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001).Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.
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| 12. |
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| 13. |
- Holmlund, Petter, 1988-, et al.
(författare)
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Posture-dependent collapse of the optic nerve subarachnoid space : A combined MRI and modeling study
- 2021
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Lindholm, Heléne, et al.
(författare)
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Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis
- 2020
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals. Methods DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in theNR3C1gene, rs1360780 in theFKBP5gene, rs53576 in theOXTRgene, 5-HTTLPR inSLC6A4gene and rs6295 in theHTR1Agene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire. Results Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants (p = 0.030 andp = 0.036, respectively). For SNP rs41423247 in theNR3C1gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele (p < 0.01). For the SNP rs53576 in theOXTRgene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele (p < 0.01). Conclusion This study shows that SNP rs41423247 in theNR3C1gene and SNP rs53576 in theOXTRgene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.
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| 18. |
- Machaczka, Maciej, et al.
(författare)
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Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: does donor T-cell engraftment 3 months after transplant predict survival?
- 2012
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Ingår i: Leukemia and Lymphoma. - : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplant (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD were 29% and 47%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplant was measured in 31 out of 34 patients (91%) surviving beyond day + 100. Seventeen patients achieved andgt; 90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with andlt;= 90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, p = 0.002) and better long-term PFS and OS (p = 0.002 and 0.046, respectively). Donor T-cell engraftment of andgt; 90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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| 19. |
- Machaczka, Maciej, et al.
(författare)
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Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden : Does donor T-cell engraftment 3 months after transplantation predict survival?
- 2012
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Ingår i: Leukemia and Lymphoma. - London : Informa Healthcare. - 1042-8194 .- 1029-2403. ; 53:9, s. 1699-1705
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight adult patients with chronic lymphocytic leukemia (CLL) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in Sweden between 1999 and 2007. The cumulative incidences of acute GVHD grades II-IV and chronic GVHD were 29% and 48%, respectively. Rates of non-relapse mortality, progression-free survival (PFS) and overall survival (OS) were 18%, 47% and 74% at 1 year, and 21%, 25% and 45% at 5 years, respectively. T-cell chimerism after transplantation was measured in 31 out of 34 patients (91%) surviving beyond day +100. Seventeen patients achieved >90% donor T-cell engraftment at 3 months after allo-SCT and, compared with the 12 patients with ≤90% donor T-cell engraftment, they showed favorable PFS at 1 year (82% vs. 33%, P=0.002), and better long-term PFS and OS (P=0.002 and 0.05 respectively). Donor T-cell engraftment of >90% at 3 months after RIC allo-SCT for CLL seems to predict favorable short-term and long-term outcome.
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| 20. |
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| 21. |
- Malm, Helene
(författare)
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Costimulation Blockade in Experimental Transplantation
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Transplantation is the only cure for end-stage organ failure. With the transplantation follows the need for continuous treatment with immunosuppressive agents for as long as the graft functions, which entails major side effects. Less toxic treatments are therefore in great demand. Preferably, the treatment should also be limited in time. The ultimate solution would be induction of tolerance to the graft. To achieve this, interference with T cell activation signals, especially blockade of costimulation molecules, has been exploited. In this thesis, blockade of costimulatory molecules in different combinations has been tested for its capacity to prolong survival of grafts of different origins in a rodent model. The mechanisms of action have also been investigated. Blockade of the CD28-B7 and ICAM-LFA-1 pathways acted synergistically in inhibiting T cell proliferation and prolonging survival of transplanted heart and skin grafts. Prolonged blockade of ICAM-LFA-1 ligation was of benefit, while on the other hand, prolonged blockade of CD28-B7 resulted in accelerated rejection of secondary skin transplants. The treatment did not induce linked suppression or dominant tolerance, in that secondary transplants of either the same tissue origin or other tissue origin were eventually rejected in the majority of cases. Moreover, a secondary transplant evoked an inflammatory reaction leading to rejection changes in the first transplant, as judged by histological examination. Combined blockade of CD40-CD40L and CD28-B7 pathways allowed survival of islet grafts for more than 100 days and on histological examination of these grafts no cellular reaction against the graft could be detected. The addition of anti-LFA-1 did not confer any benefit. Costimulation blockade was not dependent on the presence of CD4+CD25+ T cells or T cell derived IL-10 in order to mediate graft acceptance. CD4+CD25+ T cells could develop from CD4+CD25- T cells in the periphery in animals treated with costimulation blockade. Hence, a combination of two or three agents blocking different costimulatory pathways is more effective in prolonging survival of transplanted grafts than the use of either agent alone.
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| 22. |
- Malm, Helene, et al.
(författare)
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CTLA4ig induces long-term graft survival of allogeneic skin grafts and totally inhibits T-cell proliferation in LFA-1-deficient mice.
- 2002
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Ingår i: Transplantation. - 1534-6080. ; 73:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It was recently shown that some strains of mice are capable of rejecting transplants independently of B7 and CD40L signaling and that this rejection is mediated by CD8(+) T cells. LFA-1 is known to be important for CD8(+) T cell activation and cytotoxicity. Therefore, blockade of LFA-1 could be important in overcoming costimulation blockade, CD8(+) T-cell-mediated, resistant rejection. The purpose of this study was to define the effect of combined blockade of the LFA-1 and B7 costimulation pathways on the alloimmune response in mice. METHODS: Allogeneic skin transplantation was performed using BALB/c mice as donors and C57BL/6J wild-type or LFA-1-deficient (CD11a(-/-)) mice as recipients. CTLA4Ig or anti-LFA-1 was administered either as an induction or a prolonged therapy. Mixed lymphocyte reactions were conducted to study the effect of CTLA4Ig on T-cell proliferation in CD11a(-/-) mice. RESULTS AND CONCLUSIONS: Administration of CTLA4Ig completely inhibits CD11a(-/-) T-cell proliferation in response to alloantigens and significantly improved skin allograft survival in CD11a(-/-) mice. Prolonged treatment of wild-type recipient mice with CTLA4Ig and anti-LFA-1 increased median survival time to 45.5 days compared with 16 days after induction therapy, but it was not sufficient to induce indefinite allograft survival in this model.
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| 23. |
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| 24. |
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| 25. |
- Oderup, Cecilia, et al.
(författare)
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Costimulation Blockade-Induced Cardiac Allograft Tolerance: Inhibition of T Cell Expansion and Accumulation of Intragraft cD4+Foxp3+ T Cells.
- 2006
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1534-6080 .- 0041-1337. ; 82:11, s. 1493-1500
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Tidskriftsartikel (refereegranskat)abstract
- Background. Previous studies have demonstrated that anti-CD40L or anti-B7 requires the presence of CD4(+)CD25(+) regulatory T cells (Treg) to induce antigen specific hyporesponsiveness. Other tolerance strategies involving Treg have shown a dependency on interleukin (IL)-10. The objective of this study was to investigate the role of CD4(+)CD25(+) Treg and IL-10 when treating transplant recipients with cytotoxic T lymphocyte-associated antigen (CTLA)-4 immunoglobulin (Ig), anti-CD40L, and anti-lymphocyte function-associated antigen (LFA)-1. Methods. Recombinase activating gene-deficient (Rag1(-/-)) mice were transplanted with BALB/c hearts and adoptively transferred with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-)CD103(-) T cells and treated with costimulation blockade. Intragraft T cells from C57BL/6 recipients were analyzed for the expression of the Foxp3 protein after tolerance induction. Results. Mice reconstituted with IL-10(-/-) CD4(+) T cells, CD4(+)CD25(-) T cells or CD4(+)CD25(-) CD103(-) T cells and treated with costimulation blockade accepted allografts permanently. Analysis of cells from recipient mice adoptively transferred with CD4(+)CD25(-) T cells contained a population of CD4(low)CD25(+) T cells 100 days after transplantation. Costimulation blockade partially prevented the homeostatic proliferation of CD4(+)CD25(-)CD103(-) T cells in Rag-1(-/-) recipients. Accepted allografts contained an elevated number of CD4(+)Foxp3(+) T cells. Conclusions. These results indicate that T-cell derived IL-10 is not essential for induction of graft acceptance in mice treated with costimulation blockade, but that treatment limits T-cell expansion in the recipients. The results further indicate that tolerance is maintained by intragraft CD4(+)Foxp3(+) T cells.
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| 26. |
- Paul, Clara, et al.
(författare)
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Operational tolerance in nonvascularized transplant models induced by AR-C117977, a monocarboxylate transporter inhibitor.
- 2008
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Ingår i: Transplantation. - 1534-6080. ; 86:8, s. 1135-1138
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Tidskriftsartikel (refereegranskat)abstract
- AR-C117977, a monocarboxylate transporter inhibitor, reduces immune responses both in vitro and in vivo, maintains long-term graft survival, and induces operational tolerance. To evaluate the immunosuppressive limitations of AR-C117977, this study was performed in nonvascularized transplant models noted for their refractive response to standard immunosuppressive agents. Rat skin was transplanted from DA(RT1avl) into PVG(RT1c) and the reverse. Mouse islet allotransplantation was performed with BALB/c H2d donors and C57Bl/6J H2b recipients. In the skin graft model, AR-C117977 monotherapy was associated with long-term skin graft survival in one rat strain combination. AR-C117977 and cyclosporine A (CsA) in combination resulted in significant prolongation of graft survival in both rat strains. CsA monotherapy did not prevent acute rejection in either strain. Islet allograft survival was moderately prolonged with CsA or AR-C117977. AR-C117977 is an efficient immunosuppressive drug in stringent rodent transplant models and further studies are warranted.
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| 27. |
- von Scherling, Mathias, et al.
(författare)
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Rapportering till VA-databaser vid driftstörningar − med förslag till kodlista
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Driftstörningar inom VA-verksamheten ska rapporteras till en VA-databas och dokumenteras. Dokumentationen innehåller vital information för VA-organisationen som ska planera underhåll och förnyelse samt följa upp sin verksamhet. Därför är det viktigt att rapporteringen utförs konsekvent och korrekt. Hittills har rapporteringen av driftstörningsdata skett på olika sätt till olika databaser. Rapporten innehåller förslag för en mer enhetlig rapportering, förslag till en kodlista med defi nitioner samt en beskrivning av arbetsflödet.
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