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Sökning: WFRF:(Smeds J)

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  • Bergqvist, Jenny, et al. (författare)
  • Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:5, s. 845-850
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer-corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH.
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  • Martorell, X, et al. (författare)
  • Blue Gene/L performance tools
  • 2005
  • Ingår i: IBM Journal of Research and Development. - : IBM. - 0018-8646 .- 2151-8556. ; 49:2-3, s. 407-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Good performance monitoring is the basis of modern performance aualysis tools for application optimization. We are providing a variety of such performance analysis tools for the new Blue Gene(®)/L supercomputer. Those tools can be divided into two categories: single-node performance tools and multinode performance tools. Front a single-node perspectire, we provide standard interfaces and libraries, such as PAPI and libHPM, that propide access to the hardware performance counters for applications running on the Blue Gene/L compute nodes. From a multinode perspective, we focus on tools that analyze Message Passing Interface (MPI) behavior. Those tools work by first collecting message-passing trace data when a program runs. The trace data is then used by, graphical interface tools that analyze the behavior of applications. Using the current prototype tools, we demonstrate their usefulness and applicability with case studies of application optimization.
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  • Janko, Matthew R., et al. (författare)
  • In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement
  • 2022
  • Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 76:2, s. 546-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P <.001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P <.001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.
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  • Miller, LD, et al. (författare)
  • An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival
  • 2005
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 102:38, s. 13550-13555
  • Tidskriftsartikel (refereegranskat)abstract
    • Perturbations of the p53 pathway are associated with more aggressive and therapeutically refractory tumors. However, molecular assessment of p53 status, by using sequence analysis and immunohistochemistry, are incomplete assessors of p53 functional effects. We posited that the transcriptional fingerprint is a more definitive downstream indicator of p53 function. Herein, we analyzed transcript profiles of 251 p53-sequenced primary breast tumors and identified a clinically embedded 32-gene expression signature that distinguishes p53-mutant and wild-type tumors of different histologies and outperforms sequence-based assessments of p53 in predicting prognosis and therapeutic response. Moreover, the p53 signature identified a subset of aggressive tumors absent of sequence mutations in p53 yet exhibiting expression characteristics consistent with p53 deficiency because of attenuated p53 transcript levels. Our results show the primary importance of p53 functional status in predicting clinical breast cancer behavior.
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  • Smeds, J, et al. (författare)
  • Gene profile and response to treatment
  • 2005
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 0923-7534. ; 1616 Suppl 2, s. 195-202
  • Tidskriftsartikel (refereegranskat)
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  • Torrens, J., et al. (författare)
  • Advancing urban transitions and transformations research
  • 2021
  • Ingår i: Environmental Innovation and Societal Transitions. - : Elsevier. - 2210-4224. ; 41, s. 102-105
  • Forskningsöversikt (refereegranskat)abstract
    • Urban transitions and transformations research fosters a dialogue between sustainability transitions theory an inter- and transdisciplinary research on urban change. As a field, urban transitions and transformations research encompasses plural analytical and conceptual perspectives. In doing so, this field opens up sustainability transitions research to new communities of practice in urban environments, including mayors, transnational municipal networks, and international organizations.
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  • Ander, S J, et al. (författare)
  • Growth and function of human parathyroid tissue transplanted to athymic mice.
  • 1997
  • Ingår i: Journal of endocrinological investigation. - 0391-4097. ; 20:11, s. 640-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.
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  • Ander, S J, et al. (författare)
  • Revascularisation of human parathyroid tissue transplanted to athymic mice.
  • 1997
  • Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 0903-4641. ; 105:12, s. 931-40
  • Tidskriftsartikel (refereegranskat)abstract
    • The revascularisation process of transplanted human normal, hyperplastic and adenomatous parathyroid tissue was analysed at 2 and 4 days and 1, 2, 4, 7 and 12 weeks after transplantation to athymic mice. The transplants were examined by light and electron microscopy, immunohistochemistry and autoradiography. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. Immunohistochemistry demonstrated ingrowth of vessels from the host into the transplant and at one week numerous capillary sprouts were observed in the peripheral parts of the transplants. During the first week, peak levels of proliferation (labelling index) were observed in endothelial cells and capsular fibroblasts, and the proliferative capacity of endothelial cells was most pronounced in adenoma transplants. Fenestrated capillaries were observed in hyperplastic and adenomatous transplants, but not in transplants of normal tissue. In conclusion, revascularisation of transplanted human parathyroid tissue is enabled by ingrowth of vessels from the host into the transplant. The proliferative capacity of endothelial cells is higher and the process of maturation is faster in hyperplastic and adenomatous tissue compared to normal tissue.
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  • Forsblad-d'Elia, H, et al. (författare)
  • Biomechanical Properties of Common Carotid Arteries Assessed by Circumferential 2D Strain and β Stiffness Index in Patients With Ankylosing Spondylitis
  • 2021
  • Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 48:3, s. 352-360
  • Tidskriftsartikel (refereegranskat)abstract
    • Ankylosing spondylitis (AS) is associated with an elevated risk of cardiovascular disease (CVD) related to atherosclerosis, preceded by arterial stiffness. We aimed to examine common carotid artery (CCA) biomechanical properties using ultrasound to calculate β stiffness index (indicating arterial stiffness) and, a more recently developed technique, 2-dimensional (2D) speckle tracking strain (indicating arterial motion and deformation, strain) to (1) compare with age- and sex-matched controls, and (2) analyze relationships between strain and stiffness with disease characteristics and traditional risk factors for CVD in patients with AS.Methods.In this cross-sectional study, a cohort of 149 patients with AS, mean age 55.3 ± 11.2 years, 102 (68.5%) men, and 146 (98%) HLA-B27–positive, were examined. Bilateral CCA were examined for circumferential 2D strain and β stiffness index. A subgroup of 46 patients was compared with 46 age- and sex-matched controls, both groups without hypertensive disease, diabetes, myocardial infarction, or stroke.Results.Mean bilateral circumferential 2D strain was lower in AS patients compared with controls (7.9 ± 2.6% vs 10.3 ± 1.9%, P < 0.001), whereas mean bilateral β stiffness index was higher (13.1 ± 1.7 mmHg/mm vs 12.3 ± 1.3 mmHg/mm, P = 0.02). In multivariable linear regression analyses, strain was associated with age, erythrocyte sedimentation rate, history of anterior uveitis, and treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARD) and/or biological DMARD (R2 0.33), while stiffness was associated with age (R2 0.19).Conclusion.Both CCA circumferential 2D strain and β stiffness index differed between patients with AS and controls. Strain was associated with AS-related factors and age, whereas only age was associated with stiffness, suggesting that the obtained results reflect different pathogenic vascular processes.
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  • Gaupp-Berghausen, M, et al. (författare)
  • Evaluation of different recruitment methods: Longitudinal, web-based, pan-european physical activity through sustainable transport approaches (PASTA) project
  • 2019
  • Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 21:5, s. e11492-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sufficient sample size and minimal sample bias are core requirements for empirical data analyses. Combining opportunistic recruitment with a Web-based survey and data-collection platform yields new benefits over traditional recruitment approaches. Objective: This paper aims to report the success of different recruitment methods and obtain data on participants' characteristics, participation behavior, recruitment rates, and representativeness of the sample. Methods: A longitudinal, Web-based survey was implemented as part of the European PASTA (Physical Activity through Sustainable Transport Approaches) project, between November 2014 and December 2016. During this period, participants were recruited from 7 European cities on a rolling basis. A standardized guide on recruitment strategy was developed for all cities, to reach a sufficient number of adult participants. To make use of the strengths and minimize weakness, a combination of different opportunistic recruitment methods was applied. In addition, the random sampling approach was applied in the city of Örebro. To reduce the attrition rate and improve real-time monitoring, the Web-based platform featured a participant's and a researchers' user interface and dashboard. Results: Overall, 10,691 participants were recruited; most people found out about the survey through their workplace or employer (2300/10691, 21.51%), outreach promotion (2219/10691, 20.76%), and social media (1859/10691, 17.39%). The average number of questionnaires filled in per participant varied significantly between the cities (P<.001), with the highest number in Zurich (11.0, SE 0.33) and the lowest in Örebro (4.8, SE 0.17). Collaboration with local organizations, the use of Facebook and mailing lists, and direct street recruitment were the most effective approaches in reaching a high share of participants.
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  • Jarvis, Erich D., et al. (författare)
  • Whole-genome analyses resolve early branches in the tree of life of modern birds
  • 2014
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331
  • Tidskriftsartikel (refereegranskat)abstract
    • To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
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  • Kahlmeier, Sonja, et al. (författare)
  • Assessing the Policy Environment for Active Mobility in Cities—Development and Feasibility of the PASTA Cycling and Walking Policy Environment Score
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:3, s. 986-
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of setting a policy focus on promoting cycling and walking as sustainable and healthy modes of transport is increasingly recognized. However, to date a science-driven scoring system to assess the policy environment for cycling and walking is lacking. In this study, spreadsheet-based scoring systems for cycling and walking were developed, including six dimensions (cycling/walking culture, social acceptance, perception of traffic safety, advocacy, politics and urban planning). Feasibility was tested using qualitative data from pre-specified sections of semi-standardized interview and workshop reports from a European research project in seven cities, assessed independently by two experts. Disagreements were resolved by discussions of no more than 75 minutes per city. On the dimension “perception of traffic safety”, quantitative panel data were used. While the interrater agreement was fair, feasibility was confirmed in general. Validity testing against social norms towards active travel, modal split and network length was encouraging for the policy area of cycling. Rating the policy friendliness for cycling and walking separately was found to be appropriate, as different cities received the highest scores for each. Replicating this approach in a more standardized way would pave the way towards a transparent, evidence-based system for benchmarking policy approaches of cities towards cycling and walking.
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  • Papareddy, Praveen, et al. (författare)
  • A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
  • 2019
  • Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2442-2455
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-kappa B. We found that the modulating effect is primarily restricted to the less abundant beta-isoform (h beta AT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of h beta AT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or h beta AT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with h beta AT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
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  • Smeds, H, et al. (författare)
  • X-linked Malformation and Cochlear Implantation
  • 2017
  • Ingår i: Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. - 1537-4505. ; 38:1, s. 38-46
  • Tidskriftsartikel (refereegranskat)
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  • Smeds, H., et al. (författare)
  • X-linked Malformation and Cochlear Implantation
  • 2017
  • Ingår i: Otology and Neurotology. - : Ovid Technologies (Wolters Kluwer Health). - 1531-7129 .- 1537-4505. ; 38:1, s. 38-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate if cochlear implantation is safe and constitutes an option for hearing rehabilitation of children with x-linked inner ear malformation. Study Design: Retrospective patient review in combination with a multidisciplinary follow-up. Patients: Ten children with severe-profound mixed hearing loss and radiological findings consistent with Incomplete Partition type 3 cochlear malformation received cochlear implants during the years 2007 to 2015. Nine of the children had a mutation affecting the gene POU3F4 on Xq21. Main Outcome Measures: Surgical events, intraoperative measures and electrical stimulation levels, hearing and spoken language abilities. Results: In all, 15 cochlear implantations were performed. In three cases the electrode was found to be in the internal auditory canal on intraoperative x-ray and repositioned successfully. One child had a postoperative rhinorrhea confirmed to be cerebrospinal fluid but this resolved on conservative treatment. No severe complications occurred. Postoperative electrical stimulation levels were higher in 9 of 10 children, as compared with typically reported average levels in patients with a normal cochlea. Eight patients developed spoken language to various degrees while two were still at precommunication level. However, speech recognition scores were lower than average pediatric cases. Conclusion: Cochlear implantation is a safe procedure for children with severe-profound mixed hearing loss related to POU3F4 mutation inner ear malformation. The children develop hearing and spoken language but outcome is below average for pediatric CI recipients.
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  • Smeds, Karolina, et al. (författare)
  • Preferred overall loudness. I : Sound field presentation in the laboratory
  • 2006
  • Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1499-2027 .- 1708-8186. ; 45:1, s. 2-11
  • Tidskriftsartikel (refereegranskat)abstract
    • This study questions the basic assumption that prescriptive methods for nonlinear, wide dynamic range compression (WDRC) hearing aids should restore overall loudness to normal. Fifteen normal-hearing listeners and twenty-four hearing-impaired listeners (with mild to moderate hearing loss, twelve with and twelve without hearing aid experience) participated in laboratory tests. The participants first watched and listened to video sequences and rated how loud and how interesting the situations were. For the hearing-impaired participants, gain was applied according to the NAL-NL1 prescription. Despite the fact that the NAL-NL1 prescription led to less than normal overall calculated loudness, according to the loudness model of Moore and Glasberg (1997), the hearing-impaired participants rated loudness higher than the normal-hearing participants. The participants then adjusted a volume control to preferred overall loudness. Both normal-hearing and hearing-impaired participants preferred less than normal overall calculated loudness. The results from the two groups of hearing-impaired listeners did not differ significantly.
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  • Smeds, Karolina, et al. (författare)
  • Preferred overall loudness. II : Listening through hearing aids in field and laboratory tests
  • 2006
  • Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1499-2027 .- 1708-8186. ; 45:1, s. 12-25
  • Tidskriftsartikel (refereegranskat)abstract
    • In a laboratory study, we found that normal-hearing and hearing-impaired listeners preferred less than normal overall calculated loudness (according to a loudness model of Moore & Glasberg, 1997). The current study verified those results using a research hearing aid. Fifteen hearing-impaired and eight normal-hearing participants used the hearing aid in the Field and adjusted a volume control to give preferred loudness. The hearing aid logged the preferred volume control setting and the calculated loudness at that setting. The hearing-impaired participants preferred, in median, loudness levels of -14 phon re normal for input levels from 50 to 89 dB SPL. The normal-hearing participants preferred close to normal overall loudness. In subsequent laboratory tests, using the same hearing aid, both hearing-impaired and normal-hearing listeners preferred less than normal overall calculated loudness, and larger reductions for higher input levels. In summary, the hearing-impaired listeners preferred less than normal overall calculated loudness, whereas the results for the normal-hearing listeners were inconclusive.
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