| 1. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 2. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 3. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 4. |
- Radivoyevitch, Tomas, et al.
(författare)
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Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
- 2018
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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| 5. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 6. |
- Soranno, Patricia A., et al.
(författare)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 7. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 8. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Apró, William, et al.
(författare)
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Leucine does not affect mechanistic target of rapamycin complex 1 assembly but is required for maximal ribosomal protein s6 kinase 1 activity in human skeletal muscle following resistance exercise
- 2015
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 29:10, s. 4358-4373
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Tidskriftsartikel (refereegranskat)abstract
- We examined how the stimulatory effect of leucine on the mechanistic target of rapamycin complex 1 (mTORC1) pathway is affected by the presence of the remaining essential amino acids (EAAs). Nine male subjects performed resistance exercise on 4 occasions and were randomly supplied EAAs with leucine, EAAs without leucine (EAA-Leu), leucine alone, or flavored water (placebo; control). Muscle biopsies were taken from the vastus lateralis before and 60 and 90 min after exercise. Biopsies were analyzed for protein phosphorylation, kinase activity, protein-protein interactions, amino acid concentrations, and tracer incorporation. Leucine alone stimulated ribosomal protein s6 kinase 1 (S6K1) phosphorylation similar to 280% more than placebo and EAA-Leu after exercise. Moreover, this response was enhanced by 60-75% after intake of EAAs compared with that of leucine alone (P < 0.05). Kinase activity of S6K1 reflected that of S6K1 phosphorylation; 60 min after exercise, the activity was elevated 3.3- and 4.2-fold with intake of leucine alone and with EAAs, respectively (P < 0.05). The interaction between mammalian target of rapamycin and regulatory-associated protein of mammalian target of rapamycin was unaltered in response to both resistance exercise and amino acid provision. Leucine alone stimulates mTORC1 signaling, although this response is enhanced by other EAAs and does not appear to be caused by alterations inmTORC1 assembly.
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| 10. |
- Apró, William, et al.
(författare)
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Resistance exercise induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high intensity interval cycling.
- 2015
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 308:6, s. E470-E481
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Tidskriftsartikel (refereegranskat)abstract
- Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in a randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (~90%, P<0.05) but was unchanged in R. Thr389 phosphorylation of S6K1 was increased several-fold immediately after exercise (P<0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (~55% and ~110%, respectively, P<0.05) and eEF2 phosphorylation was reduced (~55%, P<0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P<0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTORC1 signaling after subsequent resistance exercise, but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.
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| 11. |
- Bejanyan, Nelli, et al.
(författare)
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Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:5, s. 945-955
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n = 109), 1 (n = 93), or 0 cycles (n = 322) of consolidation before myeloablative alloHCT from 2008 to 2012. As expected, time to alloHCT was longer with increasing cycles of consolidation. Patients receiving ≥2, 1, or 0 cycles of consolidation had an adjusted 3-year cumulative incidence of relapse of 20%, 27%, and 22%; 1-year transplant-related mortality (TRM) of 16%, 18%, and 23%; adjusted 3-year leukemia-free survival (LFS) of 54%, 48%, and 47%; and 3-year overall survival (OS) of 63%, 59%, and 54% (all P values >.40). Multivariable analysis confirmed that consolidation was not prognostic for LFS (relative risk, 1.20, 95% confidence interval, .86 to 1.67; P = .28 for no consolidation; RR, 1.18, 95% confidence interval, .79 to 1.76; P = .41 for 1 cycle versus ≥2 cycles = reference). Similarly, consolidation was not associated with OS, relapse, TRM, or graft-versus-host disease. We conclude that consolidation chemotherapy does not appear to provide added benefit in adult ALL patients with available donors who undergo myeloablative alloHCT in CR1.
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| 12. |
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| 13. |
- Bonner, Stephen, et al.
(författare)
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A review of biomedical datasets relating to drug discovery: a knowledge graph perspective
- 2022
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; In Press
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Forskningsöversikt (refereegranskat)abstract
- Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritization. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, while relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data are required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorized according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and an evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, while also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.
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| 14. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 15. |
- Carlbring, Per, et al.
(författare)
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ITSY : A Gamified One-Session Virtual Reality App With 12-Month Follow-Up Data
- 2017
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Ingår i: Program Book. ; , s. 396-396
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Konferensbidrag (refereegranskat)abstract
- Introduction: This is the first large randomized-controlled trial to evaluate whether commercially available VR hardware and software can be used for exposure therapy. The aim of this study was to compare gold-standard One Session Therapy (OST) for reduction of spider phobia symptoms and avoidance behavior using in vivo spiders and a human therapist, to a newly developed single-session gamified Virtual Reality Exposure Therapy (VRET) application with modern, consumer-available VR hardware, virtual spiders, and a virtual therapist.Method: Subjects (N=100) with spider phobia, diagnosed, and meeting inclusion criteria were recruited from the general population and randomized to 2 treatment arms. In 1-week intervals, pre-measurement, 3-hr treatment and post-measurement were completed with an in-vivo behavioral approach test (BAT) serving as the primary outcome measure for both groups. This study was powered to detect a non-inferiority margin of a 2-point between-group difference on the BAT, with a standard deviation of 4 (at 80% power).Results: 98 patients commenced treatment and 97 patients completed post-measurement. Per protocol analysis indicated VR was not non-inferior to OST. Repeated-measures ANOVA identified a significant main effect of time (p < .001) and time x group effect (p < .05). Both OST and VR participants experienced large BAT within-group effect sizes (d=2.28 and d=1.45, respectively). By the time of the conference there will be 12-month follow-up data including prediction analysis and the effect of treatment credibility and working alliance (with the virtual therapist).Conclusion: OST is the superior treatment option for spider phobia. VRET is an effective alternative if OST cannot be provided, as pure self-help, as the initial intervention in a stepped-care model, or as a possible post-OST booster.
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| 16. |
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| 17. |
- Dunleavy, Elaine M., et al.
(författare)
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A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast Centromeres
- 2007
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 28:6, s. 1029-1044
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Tidskriftsartikel (refereegranskat)abstract
- A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to known histone binding proteins NASP(Human) and N1/N2(Xenopus) and aligns with Hif1(S. cerevisiae), defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-A(Cnp1) and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-A(CnP1) at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-A(Cnp1) to accumulate at centromeres in S and G2 phase-arrested cells in a replication-independent mechanism. We propose that one function of Sim3 is to act as an escort that hands off CENP-A(Cnp1) to chromatin assembly factors, allowing its incorporation into centromeric chromatin.
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| 18. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 19. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 20. |
- Fagernäs, Simon, et al.
(författare)
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What do users think about Virtual Reality relaxation applications? A mixed methods study of online user reviews using natural language processing
- 2021
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Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- The advent of affordable Virtual Reality (VR) technology has spurred consumer and commercial interest in VR relaxation applications, which has quickly grown into a popular non-gaming genre on digital marketplaces. While laboratory studies have demonstrated efficacy of VR relaxation for mental health purposes, little is known about how users experience this type of intervention and no study has examined the reception of consumer versions among regular users in everyday life. Studying published user reviews offers a unique window into naturalistic user experiences that complements traditional qualitative methods by circumventing the sampling bias of interview studies, and allowing analyses on full samples, unconstrained by coding resources. Using an innovative, semi-automated Natural Language Processing technique, the current study analyzed 1379 published reviews (including star ratings) of 30 different VR relaxation applications available for the Oculus Go and Gear VR. The uncovered topic structure and sentiment analysis thereof suggests that users have an overall positive view of VR relaxation applications, describing them as successful in inducing immersion and relaxation, and having appreciated gamification elements. However, perceived quality varied substantially between applications that explained more variance in star ratings than specific features. Critical issues raised were both technical (e.g. “overheating”) in nature and related to specific design elements and use. Implications for the design of consumer VR applications and future research are discussed.
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| 21. |
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| 22. |
- Hamilton, William, et al.
(författare)
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Virtual spiders raise real heart rates
- 2015
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Ingår i: Abstracts from the 7th Swedish Congress on internet interventions (SWEsrii). - Linköping : Linköping University Press. ; , s. 17-17
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Virtual realities (VR) give rise to feelings of presence in virtual environments and have been proven a useful medium when treating specific phobias. For validation of the usability of VR for exposure therapy it is critical to investigate the techs capacity of activating the user physiologically. An experiment was designed with the purpose of investigating if virtual spiders in a virtual environment could cause a heightening of heart rate in the participants (N = 24). The hypothesis was that participants presumably, even those not clinically spider phobic, would get raised heart rates following the introduction of several large tarantulas in a virtual room. A virtual reality program was developed that simulated spider movement around the room and a control routine with white balls instead of spiders. The experiment was of in group design and the routines sequence was balanced. Participants heart rate, despite small sample size, was significantly higher when the spiders were present in the virtual world compared to the neutral control sequence (d=0,22).
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| 23. |
- Herrick, Ariane L, et al.
(författare)
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Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
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| 24. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 25. |
- Im, Annie, et al.
(författare)
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Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
- 2020
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:8, s. 1459-1468
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Tidskriftsartikel (refereegranskat)abstract
- Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus <29 years) was significantly associated with higher rates of grade 2 to 4 acute GVHD (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11 to 2.12; P = .01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR, 1.70; 95% CI, 1.11 to 2.62; P = .01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haplo-HCT. Our results indicate that in RIC haplo-HCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
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| 26. |
- Lindner, Philip, et al.
(författare)
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Creating state of the art, next-generation Virtual Reality exposure therapies for anxiety disorders using consumer hardware platforms : Design considerations and future directions
- 2017
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Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 46:5, s. 404-420
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Forskningsöversikt (refereegranskat)abstract
- Decades of research and more than 20 randomized controlled trials show that Virtual Reality exposure therapy (VRET) is effective in reducing fear and anxiety. Unfortunately, few providers or patients have had access to the costly and technical equipment previously required. Recent technological advances in the form of consumer Virtual Reality (VR) systems (e.g. Oculus Rift and Samsung Gear), however, now make widespread use of VRET in clinical settings and as self-help applications possible. In this literature review, we detail the current state of VR technology and discuss important therapeutic considerations in designing self-help and clinician-led VRETs, such as platform choice, exposure progression design, inhibitory learning strategies, stimuli tailoring, gamification, virtual social learning and more. We illustrate how these therapeutic components can be incorporated and utilized in VRET applications, taking full advantage of the unique capabilities of virtual environments, and showcase some of these features by describing the development of a consumer-ready, gamified self-help VRET application for low-cost commercially available VR hardware. We also raise and discuss challenges in the planning, development, evaluation, and dissemination of VRET applications, including the need for more high-quality research. We conclude by discussing how new technology (e.g. eye-tracking) can be incorporated into future VRETs and how widespread use of VRET self-help applications will enable collection of naturalistic “Big Data” that promises to inform learning theory and behavioral therapy in general.
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| 27. |
- Lindner, Philip, et al.
(författare)
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Experiences of Gamified and Automated Virtual Reality Exposure Therapy for Spider Phobia : Qualitative Study
- 2020
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Ingår i: JMIR Serious Games. - Toronto, ON, Canada : JMIR Publications Inc.. - 2291-9279. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Virtual reality exposure therapy is an efficacious treatment of anxiety disorders, and recent research suggests that such treatments can be automated, relying on gamification elements instead of a real-life therapist directing treatment. Such automated, gamified treatments could be disseminated without restrictions, helping to close the treatment gap for anxiety disorders. Despite initial findings suggesting high efficacy, very is little is known about how users experience this type of intervention.Objective: The aim of this study was to examine user experiences of automated, gamified virtual reality exposure therapy using in-depth qualitative methods.Methods: Seven participants were recruited from a parallel clinical trial comparing automated, gamified virtual reality exposure therapy for spider phobia against an in vivo exposure equivalent. Participants received the same virtual reality treatment as in the trial and completed a semistructured interview afterward. The transcribed material was analyzed using thematic analysis.Results: Many of the uncovered themes pertained directly or indirectly to a sense of presence in the virtual environment, both positive and negative. The automated format was perceived as natural and the gamification elements appear to have been successful in framing the experience not as psychotherapy devoid of a therapist but rather as a serious game with a psychotherapeutic goal.Conclusions: Automated, gamified virtual reality exposure therapy appears to be an appealing treatment modality and to work by the intended mechanisms. Findings from the current study may guide the next generation of interventions and inform dissemination efforts and future qualitative research into user experiences.
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| 28. |
- Lindner, Philip, et al.
(författare)
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Gamified, Automated Virtual Reality Exposure Therapy for Fear of Spiders : A Single-Subject Trial Under Simulated Real-World Conditions
- 2020
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Virtual Reality exposure therapy (VRET) is an evidence-based treatment of phobias and recent research suggests that this applies also to self-contained, automated interventions requiring no therapist guidance. With the advent and growing adoption of consumer VR technology, automated VR intervention have the potential to close the considerable treatment gap for specific phobias through dissemination as consumer applications, self-help at clinics, or as blended treatment. There is however a lack of translational effectiveness studies on VRET treatment effects under real-world conditions.Methods: We conducted a single-arm (n = 25), single-subject study of automated, gamified VRET for fear of spiders, under simulated real-world conditions. After setup and reading instructions, participants completed the automated, single-session treatment by themselves. Self-rated fear of spiders and quality of life served as outcome measures, measured twice before, and one and two weeks after treatment, and at a six-month follow-up. Session characteristics and user experience measures were collected at the end of the session.Results: Mixed-effects modeling revealed a significant and large (d = 1.26) effect of treatment-onset on phobia symptoms (p < .001), and a small (d = 0.49) effect on quality of life (p = .025). Results were maintained at a six-month follow-up (p > .053). The intervention was tolerable and practical. There were no significant correlations between any user experience measure and decrease in phobia symptoms (p > .209).Conclusions: An automated VRET intervention for fear of spiders showed equivalent effects on phobia symptoms under effectiveness conditions as previously reported under efficacy conditions. These results suggest that automated VRET applications are promising self-help treatments also when provided under real-world conditions.
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| 29. |
- Lindner, Philip, et al.
(författare)
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How to Treat Depression With Low-Intensity Virtual Reality Interventions : Perspectives on Translating Cognitive Behavioral Techniques Into the Virtual Reality Modality and How to Make Anti-Depressive Use of Virtual Reality–Unique Experiences
- 2019
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Depression is a common mental disorder with a large treatment gap. Low-intensity, automated virtual reality (VR) interventions (not requiring a therapist) is a scalable and promising solution now that VR is an accessible and mature, consumer technology. Yet unlike with phobias, there have been few attempts at translating evidence-based cognitive behavioral therapeutic (CBT) techniques for depression into the VR modality. In this paper, we discuss how specific CBT techniques can be made into VR experiences, including psychoeducation, behavioral activation, cognitive restructuring, and social skills training. We also discuss how VR-unique experiences, such as alternative embodiment and virtual pet interactions, can be made therapeutic. Creating a pre-clinical and clinical evidence base for these types of novel interventions should be considered a research priority, and high-quality development on par with other consumer VR applications will be essential to the success of any consumer-targeted intervention. If this is achieved, low-intensity VR interventions for depression have great potential to make an impact on public mental health.
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| 30. |
- Lindner, Philip, et al.
(författare)
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Is Continued Improvement After Automated Virtual Reality Exposure Therapy for Spider Phobia Explained by Subsequent in-vivo Exposure? : A First Test of the Lowered Threshold Hypothesis
- 2021
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Consumer Virtual Reality (VR) technology offers a powerful, immersive medium for scalable dissemination of mental health interventions. Decades of research has shown VR exposure therapy to be efficacious in the treatment of anxiety disorders and that the fear reduction generalizes to real-world stimuli. Many studies also report continued improvement over time, after discontinuing VR use. The lowered threshold hypothesis states that this continued improvement is moderated by lowering the threshold to conduct subsequent in-vivo exposure. The current study is the first to formally test this hypothesis, using data from a recent trial on automated VR exposure therapy for spider phobia, in which participants (n = 49) were followed for 1 year, completing assessments 1 week, 3 and 12 months post-treatment. The assessment included validated self-report of phobia symptoms, a standardized behavioral approach test featuring a real spider, and a questionnaire for self-reporting frequency of in-vivo exposures since last assessment. Number of in-vivo exposures was found to be independently associated with greater symptom decrease in longitudinal outcome models. In sequential structural equation models, immediate post-treatment symptom reduction was associated with subsequent in-vivo exposures, which in turn was associated with continued symptom reduction. However, this applied only to self-reported phobia symptoms (not behavioral avoidance) and no associations were found past 3 months. Our findings offer preliminary, partial support for the lowered threshold hypothesis, suggesting that VR exposure interventions may benefit from including explicit in-virtuo to in-vivotransitioning components.
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| 31. |
- Lindner, Philip, et al.
(författare)
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The Potential of Consumer-Targeted Virtual Reality Relaxation Applications : Descriptive Usage, Uptake and Application Performance Statistics for a First-Generation Application
- 2019
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Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Virtual Reality (VR) technology can be used to create immersive environments that promote relaxation and distraction, yet it is only with the recent advent of consumer VR platforms that such applications have the potential for widespread dissemination, particularly in the form of consumer-targeted self-help applications available at regular digital marketplaces. If widely distributed and used as intended, such applications have the potential to make a much-needed impact on public mental health. In this study, we report real-world aggregated uptake, usage and application performance statistics from a first-generation consumer-targeted VR relaxation application which has been publicly available for almost 2 years. While a total of 40,000 unique users signals an impressive dissemination potential, average session duration was lower than expected, and the data suggests a low number of recurrent users. Usage of headphones and auxiliary input devices was relatively low, and some application performance issues were evident (e.g., lower than intended framerate and occurrence of overheating). These findings have important implications for the design of the future VR relaxation applications, revealing primarily that user engagement needs to be addressed in the early stage of development by including features that promote prolonged and recurrent use (e.g., gamification elements).
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| 32. |
- Lindner, Philip, et al.
(författare)
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Virtual Reality exposure therapy for public speaking anxiety in routine care : a single-subject effectiveness trial
- 2021
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Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 50:1, s. 67-87
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Tidskriftsartikel (refereegranskat)abstract
- Virtual Reality (VR) can be used as a therapeutic tool to conduct efficacious in-session exposure therapy by presenting virtual equivalents of phobic stimuli, yet past hardware restrictions hindered implementation in routine care and effectiveness studies. The current study examines the effectiveness of a VR-assisted treatment protocol for public speaking anxiety with demonstrated efficacy, this time in routine care, using affordable VR hardware. Participants (n = 23) were recruited via a private clinic and treated by one of four psychologists with only minimal VR-training. Using a single-subject design and dual-slope modeling (adjusting the treatment-onset slope for treatment effects), we found a significant, large decrease in self-rated public speaking anxiety following the primary three-hour session, similar in magnitude to the previous efficacy trial. Multilevel modeling of in-session process measures suggests that the protocol works as intended, by decreasing catastrophic belief expectancy and distress, and increasing perceived performance quality. Adherence to the online transition program that followed-encouraging in-vivo exposure-was relatively poor, yet symptoms decrease continued. No change was observed over the three-month follow-up period. We conclude that VR exposure therapy can be effective under routine care conditions and is an attractive approach for future, large-scale implementation and effectiveness trials.
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| 33. |
- McAdam, Maura, et al.
(författare)
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Learning in a Family Business Through Intermarriage : A Rhetorical History Perspective
- 2023
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Ingår i: Family Business Review. - : Sage Publications. - 0894-4865 .- 1741-6248. ; 36:1, s. 63-83
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Tidskriftsartikel (refereegranskat)abstract
- We use concepts from rhetorical history and mnemonic communities to expand on the notion of “intermarriage” in a family business as the merger of shared histories among family members, nonfamily members, and individuals from other families and suggest that a common mnemonic narrative defines the parameters of the family business rather than the structural properties of the firm or the genetic relationships among family members. Our analysis reveals how fundamental family business practices can be changed when confronted with the intimate knowledge of the rhetorical history of the failure of others.
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| 34. |
- Middleton, Michael, et al.
(författare)
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Quantifying Abdominal Adipose Tissue and Thigh Muscle Volume and Hepatic Proton Density Fat Fraction : Repeatability and Accuracy of an MR Imaging–based, Semiautomated Analysis Method
- 2017
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Ingår i: Radiology. - : Radiological Society of North America, Inc.. - 0033-8419 .- 1527-1315. ; 283:2, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study was to determine the repeatability and accuracy of an commercially available (Advanced MR Analytics [AMRA®]; Linköping, Sweden) magnetic resonance imaging (MRI)-based, semi-automated method to quantify abdominal adipose tissue and thigh muscle volume as well as hepatic proton density fat fraction (PDFF)Materials and MethodsThis prospective study was approved by an institutional review board (IRB) and was Health Insurance Portability and Accountability Act (HIPAA) compliant. All subjects provided written informed consent. Inclusion criteria were age ≥ 18 years, and willingness to participate. Exclusion criteria were contraindication to MRI. Three-dimensional, T1-weighted, dual-echo body-coil images were acquired from base of skull to knees at 3T, twice before and once after taking subjects off the scanner table (total of three acquisitions). Source images were reconstructed offline to generate water, and calibrated fat images where pure adipose tissue has unit value and absence of adipose tissue has zero value. Abdominal adipose tissues and thigh muscles were segmented, and their volumes estimated using AMRA a semi-automated analysis method and, as a reference standard, manually. Hepatic PDFF was estimated using a confounder-corrected chemical-shift encoded MRI method with hybrid complex-magnitude reconstruction., and, as a reference standard, with magnetic resonance spectroscopy (MRS). Tissue volume and hepatic PDFF intra- and inter-examination repeatability was assessed by intraclass correlation (ICC) and coefficient of variation (CV) analysis. Tissue volume and hepatic PDFF accuracies were assessed by linear regression using their respective reference standards.ResultsTwenty adult subjects were enrolled (18 female, age range 25 - 76 yrs, body mass index range 19.3 to 43.9 kg/m2). Adipose and thigh muscle tissue volumes estimated using the semi-automated analysis method had intra-and inter-examination ICCs between 0.996 and 0.998, and CVs between 1.5 and 3.6%. For hepatic MRI PDFF, intra- and inter-examination ICCs were ≥ 0.994 and CVs, ≤ 7.3%. Agreement between semi-automated and manual volume estimates, and between MRI and MRS hepatic PDFF estimates, was high, with regression slopes and intercepts not significantly different from the identity line (all p’s > 0.05), and R2’s between 0.744 and 0.994.ConclusionsThis MRI-based, semi-automated method provides high repeatability, and high accuracy for estimating abdominal adipose tissue and thigh muscle volumes, and hepatic PDFF.
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| 35. |
- Middleton, Michael, et al.
(författare)
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Repeatability and accuracy of a novel, MRI-based, semi-automated analysis method for quantifying abdominal adipose tissue and thigh muscle volumes
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Current MRI methods to estimate body tissue compartment volumes rely on manual segmentation, which is laborious, expensive, not widely available outside specialized centers, and not standardized. To address these concerns, a novel, semi-automated image analysis method has been developed. Image acquisition takes about six minutes, and uses widely available MRI pulse sequences. We found that this method permits comprehensive body compartment analysis and provides high repeatability and accuracy. Current and future clinical and drug development studies may benefit from this methodology, as may clinical settings where monitoring change in these measures is desired.
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| 36. |
- Miloff, Alexander, et al.
(författare)
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Automated virtual reality exposure therapy for spider phobia vs. in-vivo one-session treatment : A randomized non-inferiority trial
- 2019
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 118, s. 130-140
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Tidskriftsartikel (refereegranskat)abstract
- This study compared the efficacy of a technician-assisted single-session virtual reality exposure therapy (VRET) for the treatment of spider phobia featuring low-cost consumer-available hardware and novel automated software to gold-standard in-vivo one-session treatment (OST), using a parallel group randomized non-inferiority design. Method Participants (N = 100) were randomized to VRET and OST arms. Assessors blinded to treatment allocation evaluated participants at pre- and post-treatment as well follow-up (3 and 12 months) using a behavioral approach test (BAT) and self-rated fear of spider, anxiety, depression and quality-of-life scales. A maximum post-treatment difference of 2-points on the BAT qualified as non-inferiority margin. Results Linear mixed models noted large, significant reductions in behavioral avoidance and self-reported fear in both groups at post-treatment, with VRET approaching the strong treatment benefits of OST over time. Non-inferiority was identified at 3- and 12- months follow-up but was significantly worse until 12-months. There was no significant difference on a questionnaire measuring negative effects. Conclusions Automated VRET efficaciously reduced spider phobia symptoms in the short-term and was non-inferior to in-vivo exposure therapy in the long-term. VRET effectiveness trials are warranted to evaluate real-world benefits and non-specific therapeutic factors accruing from the presence of a technician during treatment. ClinicalTrials.gov (NCT02533310).
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| 37. |
- Miloff, Alexander, et al.
(författare)
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Is virtual reality treatment for spider phobia noninferior to traditional one-session treatment? The results of a randomized-controlled trial
- 2016
-
Ingår i: EABCT 2016 Abstract Book. ; , s. 753-753
-
Konferensbidrag (populärvet., debatt m.m.)abstract
- This is the first large randomized-controlled trial to evaluate whether commercially available VR hardware and software can be used for exposure therapy. The aim of this study is to compare gold-standard One Session Treatment (OST) for reduction of spider phobia symptoms and avoidance behaviour using in vivo spiders and a human therapist, to a newly developed single-session gamified Virtual Reality Exposure Therapy (VRET) application with modern, consumer-available VR hardware, virtual spiders, and a virtual therapist. Subjects (N = 100) with spider phobia, diagnosed, and meeting inclusion criteria were recruited from the general population and randomized to 2 treatment arms. In 1-week intervals, pre-measurement, 3-hr treatment and post-measurement were completed with an in-vivo behavioral approach test (BAT) serving as the primary outcome measure for both groups. This study was powered to detect a non-inferiority margin of a 2-point between-group difference on the BAT, with a standard deviation of 4 (at 80% power). 98 patients commenced treatment and 97 patients completed post-measurement. Per protocol analysis indicated VR was not non-inferior to OST. Repeated-measures ANOVA identified a significant main effect of time (p < .001) and time x group effect (p < .05). Both OST and VR participants experienced large BAT within-group effect sizes (d = 2.28 and d = 1.45, respectively). OST is the superior treatment option for spider phobia. VRET is an effective alternative if OST cannot be provided, as pure self-help, as the initial intervention in a stepped-care model, or as a possible post-OST booster. Future studies will benefit from evaluating effectiveness of VRET when conducted at home.
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| 38. |
- Miloff, Alexander, et al.
(författare)
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Measuring Alliance Toward Embodied Virtual Therapists in the Era of Automated Treatments With the Virtual Therapist Alliance Scale (VTAS) : Development and Psychometric Evaluation
- 2020
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Ingår i: Journal of Medical Internet Research. - Toronto, ON, Canada : JMIR Publications Inc.. - 1438-8871. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Automated virtual reality exposure therapies (VRETs) are self-help treatments conducted by oneself and supported by a virtual therapist embodied visually and/or with audio feedback. This simulates many of the nonspecific relational elements and common factors present in face-to-face therapy and may be a means of improving adherence to and efficacy of self-guided treatments. However, little is known about alliance toward the virtual therapist, despite alliance being an important predictor of treatment outcome.Objective: In this study, we aimed to evaluate the first alliance instrument developed for use with embodied virtual therapists in an automated treatment format—the Virtual Therapist Alliance Scale (VTAS)—by (1) assessing its psychometric properties, (2) verifying the dimensionality of the scale, and (3) determining the predictive ability of the scale with treatment outcome.Methods: A psychometric evaluation and exploratory factor analysis of the VTAS was conducted using data from two samples of spider-fearful patients treated with VRET and the help of an embodied, voice-based virtual therapist (n=70). Multiple regression models and bivariate correlations were used to assess the VTAS relationship with treatment outcome, according to self-reported fear and convergence with presence and user-friendliness process measures.Results: The VTAS showed a sound two-factor solution composed of a primary factor covering task, goal, and copresence; adequate internal consistency; and good convergent validity, including moderate correlation (r=.310, P=.01) with outcomes over follow-up.Conclusions: These preliminary results suggest that alliance toward a virtual therapist is a significant predictor of treatment outcome, favors the importance of a task-goal over bond-factor, and should be explored in studies with larger sample sizes and in additional forms of embodiment.
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| 39. |
- Miloff, Alexander, et al.
(författare)
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Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy : study protocol for a randomized controlled non-inferiority trial
- 2016
-
Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facilitating access, decreasing cost, and increasing acceptability and effectiveness. The aim of this study is to compare traditional OST with in vivo spiders and a human therapist with a newly developed single-session gamified VR exposure therapy application with modern VR hardware, virtual spiders, and a virtual therapist. Methods/design: Participants with specific phobia to spiders (N = 100) will be recruited from the general public, screened, and randomized to either VR exposure therapy (n = 50) or traditional OST (n = 50). A behavioral approach test using in vivo spiders will serve as the primary outcome measure. Secondary outcome measures will include spider phobia questionnaires and self-reported anxiety, depression, and quality of life. Outcomes will be assessed using a non-inferiority design at baseline and at 1, 12, and 52 weeks after treatment. Discussion: VR exposure therapy has previously been evaluated as a treatment for specific phobias, but there has been a lack of high-quality randomized controlled trials. A new generation of modern, consumer-ready VR devices is being released that are advancing existing technology and have the potential to improve clinical availability and treatment effectiveness. The VR medium is also particularly suitable for taking advantage of recent phobia treatment research emphasizing engagement and new learning, as opposed to physiological habituation. This study compares a market-ready, gamified VR spider phobia exposure application, delivered using consumer VR hardware, with the current gold standard treatment. Implications are discussed.
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| 40. |
- Miloff, Alexander, et al.
(författare)
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VIMSE - Gamified exposure therapy for use on modern VR headsets
- 2015
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Ingår i: SWEsrii 2015. ; , s. 17-17
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- VIMSE is a new spider phobia exposure application developed for use on next generation VR headsets. Developed by Mimerse AB for the Stockholm University Department of Psychology the application advances exposure technology along a number of important fronts. VIMSE uses gamification to increase user engagement and learning, is fully automated with a virtual therapist to allow at home-self care, contains multiple open-ended environments and lighting to ensure exposure in multiple contexts, as well as a range of spiders, spider behaviors and stimuli intensity levels to ensure gradually increasing exposure levels. Collaboration with a for-profit corporation ensures the application is market-ready and scalable rather than restricted to a research environment. VIMSE is currently completing clinical trials comparing it to gold-standard one session therapy phobia treatment in a group of 100 spider phobics.
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| 41. |
- Peytrignet, Sébastien, et al.
(författare)
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Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.
- 2018
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 57:2, s. 370-381
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features.Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined.The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001).The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.
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| 42. |
- Pilla, Rachel M., et al.
(författare)
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Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.
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| 43. |
- Pilla, Rachel M., et al.
(författare)
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Global data set of long-term summertime vertical temperature profiles in 153 lakes
- 2021
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Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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| 44. |
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| 45. |
- Saad, Ayman, et al.
(författare)
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Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 25:9, s. 1875-1883
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Tidskriftsartikel (refereegranskat)abstract
- Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3(+) T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3(+) T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3(+) T cell dose cutoff of 14 x 10(7) cells/kg identified MSD/low CD3(+) (n = 223) and MSD/high CD3(+) (n = 1214), and a dose of 15 x 107 cells/kg identified MUD/low (n = 197) and MUD/high CD3(+) (n = 1102). On univariate analysis, the MSD/high CD3(+) group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3(+) group (33% versus 25%; P=.009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3(+) group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3(+) group (49% versus 41%; P=.04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3(+) T cell dose and the risk of either aGVHD grade II-IV (P=.10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4(+) T cells, CD8(+) T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3(+) T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4(+) and CD8(+) T cell doses were not possible given our small sample size. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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| 46. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 47. |
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| 48. |
- Valle, Xavier, et al.
(författare)
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Muscle Injuries in Sports: A New Evidence-Informed and Expert Consensus-Based Classification with Clinical Application.
- 2017
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Ingår i: Sports medicine (Auckland, N.Z.). - : Springer Science and Business Media LLC. - 1179-2035 .- 0112-1642. ; 47:7, s. 1241-1253
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Tidskriftsartikel (refereegranskat)abstract
- Muscle injuries are among the most common injuries in sport and continue to be a major concern because of training and competition time loss, challenging decision making regarding treatment and return to sport, and a relatively high recurrence rate. An adequate classification of muscle injury is essential for a full understanding of the injury and to optimize its management and return-to-play process. The ongoing failure to establish a classification system with broad acceptance has resulted from factors such as limited clinical applicability, and the inclusion of subjective findings and ambiguous terminology. The purpose of this article was to describe a classification system for muscle injuries with easy clinical application, adequate grouping of injuries with similar functional impairment, and potential prognostic value. This evidence-informed and expert consensus-based classification system for muscle injuries is based on a four-letter initialism system: MLG-R, respectively referring to the mechanism of injury (M), location of injury (L), grading of severity (G), and number of muscle re-injuries (R). The goal of the classification is to enhance communication between healthcare and sports-related professionals and facilitate rehabilitation and return-to-play decision making.
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| 49. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 50. |
- Wu, Lang, et al.
(författare)
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Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk : A Transcriptome-Wide Association Study in over 140,000 European Descendants
- 2019
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 79:13, s. 3192-3204
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 x 10(-6), a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 x 10(-6) after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. Significance: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
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