| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Landin-Olsson, Mona, et al.
(författare)
-
Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
-
Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p < 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.
|
|
| 5. |
|
|
| 6. |
- Sun, Chengjun, et al.
(författare)
-
CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
-
Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
|
|
| 7. |
- Sanjeevi, Carani B., et al.
(författare)
-
The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
-
Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
|
|
| 8. |
- Sedimbi, S. K., et al.
(författare)
-
SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
-
Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
-
Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
|
|
| 9. |
- Semb, G, et al.
(författare)
-
Erratum
- 2017
-
Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
- Shin, J. H., et al.
(författare)
-
IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
-
Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
-
Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
|
|
| 11. |
|
|
| 12. |
- Gyllenberg, A, et al.
(författare)
-
Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
-
Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
-
Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
|
|
| 13. |
- Hartley, Philippa, et al.
(författare)
-
SKA Science Data Challenge 2: analysis and results
- 2023
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 1967-1993
-
Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array Observatory (SKAO) will explore the radio sky to new depths in order to conduct transformational science. SKAO data products made available to astronomers will be correspondingly large and complex, requiring the application of advanced analysis techniques to extract key science findings. To this end, SKAO is conducting a series of Science Data Challenges, each designed to familiarize the scientific community with SKAO data and to drive the development of new analysis techniques. We present the results from Science Data Challenge 2 (SDC2), which invited participants to find and characterize 233 245 neutral hydrogen (H i) sources in a simulated data product representing a 2000 h SKA-Mid spectral line observation from redshifts 0.25-0.5. Through the generous support of eight international supercomputing facilities, participants were able to undertake the Challenge using dedicated computational resources. Alongside the main challenge, 'reproducibility awards' were made in recognition of those pipelines which demonstrated Open Science best practice. The Challenge saw over 100 participants develop a range of new and existing techniques, with results that highlight the strengths of multidisciplinary and collaborative effort. The winning strategy - which combined predictions from two independent machine learning techniques to yield a 20 per cent improvement in overall performance - underscores one of the main Challenge outcomes: that of method complementarity. It is likely that the combination of methods in a so-called ensemble approach will be key to exploiting very large astronomical data sets.
|
|
| 14. |
|
|
| 15. |
- Lindehammer, Sabina, et al.
(författare)
-
Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
-
Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
|
|
| 16. |
- Persson, S., et al.
(författare)
-
Burden of established cardiovascular disease in people with type 2 diabetes and matched controls : hospital-based care, days absent from work, costs, and mortality
- 2021
-
Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:Suppl. 1, s. 17-17
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Established cardiovascular disease (eCVD) is associated with need for healthcare interventions, reduced work capacity and excess mortality. People with type 2 diabetes have increased risk and earlier onset of eCVD compared to people in general. The objective was to assess the burden of hospital-based care, days absent from work, associated costs, and excess mortality for people with type 2 diabetes with and without eCVD with comparison to matched controls.Materials and methods: The study used a Swedish retrospective data-base cross-linking longitudinal individual-level data (2007-2016) from national population-based health, social insurance, and socio-economic registers for 454,983 people with type 2 diabetes and their matched controls (5:1 on year of birth, sex, and region of residence). Statuse CVD (coronary artery disease, stroke, amputation, periphery vascular disease, non-fatal cardiac arrest, or related interventions) was derivedf rom retrospective data 1997-2006 and updated at change of status 2007-2016. Use of hospital-based care, days absent from work (calendar days) and mortality used data 2007-2016. Regression analysis accounting for individual-level clustering was used for comparison to controls and to attribute costs of hospital-based care and days absent from work to eCVD and to individual complications considering multimorbidity. Excess mortality adjusted for age, sex, and educational level was attributed to eCVD using Cox proportional hazards.Results: Thirty percent (n=136,135) of people with type 2 diabetes up to age 70 years were observed with eCVD≥1 observation year in 2007-2016 (women 24% n=43,847; men 34% n=92,288). The mean annual costs of hospital-based care for diabetes complications were EUR 2,758 (95% CI 2,729 to 2,787) of which EUR 2,461 (95% CI 2,432 to 2,490)were attributed to people with eCVD (89%). Main drivers of costs of hospital-based care for people withe CVD were acute myocardial infarction, angina pectoris, and stroke; but also end-stage renal disease (ESRD) andeye disease confirming that eCVD is associated with an increased burden from other complications. eCVD was a leading cause behind work absence for both diabetes and controls. People with type 2 diabetes <66 years had on average 146 days absent (95% CI 145-147) of which 68 days (47%) were attributed to eCVD. Controls had 106 days absent of which 63 days (59%) were attributed to eCVD. The annual cost of eCVD work absence was EUR 9,337 (95% CI 9,150 to9,523) per individual. The highest work absence was attributed to ESRD, stroke, and heart failure. Type 2 diabetes without eCVD did not differ from controls regarding mortality risk, but type 2 diabetes with eCVD had a four-fold risk of death hazard rate 4.13 (95% CI 4.10 to 4.18) adjusting for age, sex, and educational level.Conclusion: This study assessed the size of the burden of eCVD-status in people with type 2 diabetes in three measures: 1) eCVD was associated with excess mortality; 2) 9 out of 10 EUR spent on hospital-based care for diabetes complications; and 3) even higher costs of days absent from work in the long-run. Reducing the risks of living with eCVD and post-poning the onset of eCVD remain central goals to reduce the burden of type 2 diabetes on the individual and on society.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Buena-Atienza, E, et al.
(författare)
-
De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy
- 2016
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28253-
-
Tidskriftsartikel (refereegranskat)abstract
- X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
|
|
| 23. |
- Cowie, A. L., et al.
(författare)
-
Applying a science-based systems perspective to dispel misconceptions about climate effects of forest bioenergy
- 2021
-
Ingår i: Global Change Biology Bioenergy. - : John Wiley and Sons Inc. - 1757-1693 .- 1757-1707. ; 13:8, s. 1210-1231
-
Tidskriftsartikel (refereegranskat)abstract
- The scientific literature contains contrasting findings about the climate effects of forest bioenergy, partly due to the wide diversity of bioenergy systems and associated contexts, but also due to differences in assessment methods. The climate effects of bioenergy must be accurately assessed to inform policy-making, but the complexity of bioenergy systems and associated land, industry and energy systems raises challenges for assessment. We examine misconceptions about climate effects of forest bioenergy and discuss important considerations in assessing these effects and devising measures to incentivize sustainable bioenergy as a component of climate policy. The temporal and spatial system boundary and the reference (counterfactual) scenarios are key methodology choices that strongly influence results. Focussing on carbon balances of individual forest stands and comparing emissions at the point of combustion neglect system-level interactions that influence the climate effects of forest bioenergy. We highlight the need for a systems approach, in assessing options and developing policy for forest bioenergy that: (1) considers the whole life cycle of bioenergy systems, including effects of the associated forest management and harvesting on landscape carbon balances; (2) identifies how forest bioenergy can best be deployed to support energy system transformation required to achieve climate goals; and (3) incentivizes those forest bioenergy systems that augment the mitigation value of the forest sector as a whole. Emphasis on short-term emissions reduction targets can lead to decisions that make medium- to long-term climate goals more difficult to achieve. The most important climate change mitigation measure is the transformation of energy, industry and transport systems so that fossil carbon remains underground. Narrow perspectives obscure the significant role that bioenergy can play by displacing fossil fuels now, and supporting energy system transition. Greater transparency and consistency is needed in greenhouse gas reporting and accounting related to bioenergy.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Edlund, Petra, et al.
(författare)
-
The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Ersek, K, et al.
(författare)
-
Costs of dementia in Hungary
- 2010
-
Ingår i: The journal of nutrition, health & aging. - : Springer Science and Business Media LLC. - 1760-4788 .- 1279-7707. ; 14:8, s. 633-639
-
Tidskriftsartikel (refereegranskat)
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Godoy, Patricio, et al.
(författare)
-
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
- 2013
-
Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 87:8, s. 1315-1530
-
Forskningsöversikt (refereegranskat)abstract
- This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4 alpha, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4 alpha), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Heggebo, L. C., et al.
(författare)
-
Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden
- 2023
-
Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life.Methods and analysisPRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints.Ethics and disseminationTo implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.Trial registration numberClinicalTrials.gov Registry (NCT05190172).
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Kjaergaard, M., et al.
(författare)
-
Demonstration of Density Matrix Exponentiation Using a Superconducting Quantum Processor
- 2022
-
Ingår i: Physical Review X. - 2160-3308. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Quantum computers hold the potential to outperform classical supercomputers at certain tasks. To implement algorithms on a quantum computer, programmers use conventional computers and hardware to create a set of classical control signals that implement a desired quantum algorithm. However, feeding the quantum information forward requires an inefficient conversion: extraction of quantum information, conversion to classical control signals, and reinjection of those signals into the system to implement quantum operations. Here, we demonstrate a more natively quantum strategy to programming quantum computers. Our approach uses the density matrix exponentiation (DME) protocol, a general technique for using a quantum state to enact a quantum operation. It can be thought of as a subroutine with which programmers can turn multiple copies of a quantum state into instructions for next steps in a quantum algorithm.We implement DME using two qubits in a superconducting quantum processor. Our implementation relies on a high-fidelity two-qubit gate and a novel technique called quantum measurement emulation to approximately reset a known quantum state. These developments enable us to demonstrate the DME protocol for the first time on a small-scale quantum processor and benchmark its performance.While DME was originally proposed in the context of a specific quantum machine-learning algorithm, it may also represent a fundamentally different approach to quantum programming. It allows the possibility of encoding quantum algorithms directly into quantum states and executing those algorithms on other quantum states, enabling a new class of efficient quantum algorithms.
|
|
| 44. |
- Ladds, MJGW, et al.
(författare)
-
Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2071-
-
Tidskriftsartikel (refereegranskat)abstract
- The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Amyloid-β metabolism in Niemann-Pick C disease models and patients.
- 2012
-
Ingår i: Metabolic brain disease. - : Springer Science and Business Media LLC. - 1573-7365 .- 0885-7490. ; 27:4, s. 573-85
-
Tidskriftsartikel (refereegranskat)abstract
- Niemann-Pick type C (NPC) is a progressive neurodegenerative lysosomal disease with altered cellular lipid trafficking. The metabolism of amyloid-β (Aβ) - previously mainly studied in Alzheimer's disease - has been suggested to be altered in NPC. Here we aimed to perform a detailed characterization of metabolic products from the amyloid precursor protein (APP) in NPC models and patients. We used multiple analytical technologies, including immunoassays and immunoprecipitation followed by mass spectrometry (IP-MS) to characterize Aβ peptides and soluble APP fragments (sAPP-α/β) in cell media from pharmacologically (U18666A) and genetically (NPC1 ( -/- ) ) induced NPC cell models, and cerebrospinal fluid (CSF) from NPC cats and human patients. The pattern of Aβ peptides and sAPP-α/β fragments in cell media was differently affected by NPC-phenotype induced by U18666A treatment and by NPC1 ( -/- ) genotype. U18666A treatment increased the secreted media levels of sAPP-α, AβX-40 and AβX-42 and reduced the levels of sAPP-β, Aβ1-40 and Aβ1-42, while IP-MS showed increased relative levels of Aβ5-38 and Aβ5-40 in response to treatment. NPC1 ( -/- ) cells had reduced media levels of sAPP-α and Aβ1-16, and increased levels of sAPP-β. NPC cats had altered CSF distribution of Aβ peptides compared with normal cats. Cats treated with the potential disease-modifying compound 2-hydroxypropyl-β-cyclodextrin had increased relative levels of short Aβ peptides including Aβ1-16 compared with untreated cats. NPC patients receiving β-cyclodextrin had reduced levels over time of CSF Aβ1-42, AβX-38, AβX-40, AβX-42 and sAPP-β, as well as reduced levels of the axonal damage markers tau and phosphorylated tau. We conclude that NPC models have altered Aβ metabolism, but with differences across experimental systems, suggesting that NPC1-loss of function, such as in NPC1 ( -/- ) cells, or NPC1-dysfunction, seen in NPC patients and cats as well as in U18666A-treated cells, may cause subtle but different effects on APP degradation pathways. The preliminary findings from NPC cats suggest that treatment with cyclodextrin may have an impact on APP processing pathways. CSF Aβ, sAPP and tau biomarkers were dynamically altered over time in human NPC patients.
|
|
| 50. |
- Meyer, E., et al.
(författare)
-
The state of the art in beyond 5G distributed massive multiple-input multiple-output communication system solutions
- 2022
-
Ingår i: Open Research Europe. - : F1000 Research Ltd. - 2732-5121. ; 2
-
Forskningsöversikt (refereegranskat)abstract
- Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal pro- cessing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on be- yond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.
|
|
