1. |
- Alvez, Maria Bueno, et al.
(author)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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2. |
- Åkerfeldt, Anna, et al.
(author)
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"Fridolin backar in i framtiden om digitala läromedel"
- 2021
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In: Dagens Nyheter. - 1101-2447. ; :2021-12-16
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Journal article (pop. science, debate, etc.)abstract
- Ingress: 23 forskare inom it- och utbildningsområdet: Regeringens utredare borde inte lyfta fram läsning på skärm som något negativt.Forskning visar att både tryckta och digitala läromedel behövs i skolan.
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5. |
- Balkhed, Wile, et al.
(author)
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Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease : A long-term follow-up study
- 2022
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In: Liver international (Print). - Chichester, United Kingdom : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 42:7, s. 1546-1556
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Journal article (peer-reviewed)abstract
- Background and Aims: The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.Methods. We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR).Results: One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%.Conclusions: Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.
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6. |
- Brænne, Ingrid, et al.
(author)
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Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
- 2021
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11, s. 1-13
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Journal article (peer-reviewed)abstract
- Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain largely unknown. We hypothesized that genetic and environmental risk factors can both contribute to T1D through dynamic alterations of molecular interactions in physiologic networks. To test this hypothesis, we utilized longitudinal blood transcriptomic profiles in The Environmental Determinants of Diabetes in the Young (TEDDY) study to generate gene co-expression networks. In network modules that contain immune response genes associated with T1D, we observed highly dynamic differences in module connectivity in the 600 days (~ 2 years) preceding clinical diagnosis of T1D. Our results suggest that gene co-expression is highly plastic and that connectivity differences in T1D-associated immune system genes influence the timing and development of clinical disease.
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7. |
- Cederborg, Anna, 1976, et al.
(author)
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Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus
- 2022
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In: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658. ; 54:8, s. 1076-1083
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Journal article (peer-reviewed)abstract
- Background: Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. Aim: To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. Methods: In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10–15 ng/mL, and corticosteroids, n = 203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5–8 ng/mL, delayed until day three, and mycophenolate mofetil 2000 mg/day, n = 343). Results: Mean mGFR was similar between groups at wait-listing (85.3 vs 84.1 ml/min/1.73m², p = 0.60), but higher in the revised treatment group at 3 (56.8 vs 63.4 ml/min/1.73m², p = 0.004) and 12 months post-transplant (60.9 vs 69.7 ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p = 0.01). Conclusion: Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death. © 2021
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8. |
- Cedervall, Ylva, et al.
(author)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Journal article (peer-reviewed)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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9. |
- Insulander, Eva, 1972-, et al.
(author)
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Conceptualizing design in research
- 2024
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In: Designs for Learning 2024: Conceptualizing design. - Stockholm : Stockholms universitet, IPD. ; , s. 7-7
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Conference paper (other academic/artistic)abstract
- During this session we will present some of the work done by the Designs for Learning research group – from the first DFL conference in 2008 with focus on “defining the field” to this conference with the focus on “conceptualizing design in research”. Firstly, we will outline some basic theoretic concepts within our design-oriented, multimodal perspective. Secondly, in the form of a dialogue, we will discuss how this perspective has been used in different empirical studies of for example textbooks and digital learning resources, subject-oriented studies of teaching and learning, museum studies of exhibitions and of visitor’s meaning-making, studies of toys and games, as well as of collaborative work between researchers and professionals. Finally, we will give some hints of theoretical challenges, including ethical commitments, and thoughts about future research engagements.
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10. |
- Olsson, Fredrik, et al.
(author)
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Neuromuscular Controller Models for Quantifying Standing Balance in Older People : A Systematic Review
- 2023
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In: IEEE Reviews in Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1941-1189 .- 1937-3333. ; 16, s. 560-578
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Research review (peer-reviewed)abstract
- Objective quantification of the balancing mechanisms in humans is strongly needed in health care of older people, yet is largely missing among current clinical balance assessment methods. Hence, the main goal of this literature review is to identify methods that have the potential to meet that need. We searched in the PubMed and IEEE Xplore databases using predefined criteria, screened 1064 articles, and systematically reviewed and categorized methods from 73 studies that deal with identification of neuromuscular controller models of human upright standing from empirical data. These studies were then analyzed with the particular aim to understand to what degree such methods would be useful solutions for assessing the balance of older individuals aged above 60 years. The 16 studies that included an older subject population were especially examined with this in mind. The majority of the reviewed articles focused on research questions related to the general function of human balance control rather than clinical applicability. Further efforts need to be made to adapt these methods for more accessible and mobile technologies and to ensure that the outcomes are valid for balance assessment of a general older population.
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11. |
- Vessby, Johan, 1972-, et al.
(author)
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AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis
- 2022
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In: Clinical and Translational Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 2155-384X. ; 13:5
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue.METHODS: Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry.RESULTS: In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC.DISCUSSION: We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance.
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12. |
- Vessby, Johan, 1972-
(author)
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Studies of ulcerative colitis with concomitant primary sclerosing cholangitis : Beyond the clinical phenotype
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Inflammatory bowel disease (IBD) is a group of chronically relapsing immune-related disorders, engaging the gastrointestinal tract. Symptoms vary depending on inflammatory phenotype, but may include diarrhoea, bowel pain and weight loss. The two most common entities are Crohn's disease and ulcerative colitis (UC). A minority of IBD patients, particularly UC, is concomitantly affected by primary sclerosing cholangitis (PSC) – an inflammatory bile duct disease with dismal prognosis. IBD with associated PSC has distinct clinical features, and is regarded a unique IBD phenotype (PSC-IBD or PSC-UC). These features include higher rates of pancolitis, a milder clinical course, and an unexplained increased risk of colorectal neoplasia.This thesis aimed to compare immunological conditions in PSC-UC and UC, but also to search for molecular differences, potentially facilitating PSC-UC diagnosis.In paper I and II, we compared eosinophil and lymphocyte activation and regulation. PSC-UC had down-regulated mucosal eosinophil activity, during both flare and remission. Compared with UC, PSC-UC had a dampened, and less Th2 dominated mucosal immune response. This was evident by a low quote of CRTH2/CXCR3 CD4+ cells and a cytokine milieu with no upregulated Th2 cytokines. In contrast, PSC-UC had highly up-regulated cytokines in peripheral blood. Among these, sCD40 stood out as being most important for inter-group separation according to multivariate analysis.In paper III, we gave a detailed description of colonic tissue factor (TF) expression. We found discrepancies in TF depending on UC subtype and inflammatory status, where inflammation- associated TF up-regulation was detected in UC only. Also, we identified stromal TF deposition as a sensitive indicator of acute colitis.In paper IV, PSC-UC and UC intestinal proteomes were compared using LC-MS/MS. After detecting more than 7200 unique proteins in the discovery step, the top-five most distinctive findings were chosen for verification. Of these, AGPAT1 was verified, being significantly higher in PSC-UC. Despite phenotypical differences, the overall colonic proteome comparison showed high degree of concordance.In summary, this thesis demonstrates distinct immunological and molecular properties in PSC-UC, implying phenotypical features beyond clinical observations. Moreover, serum sCD40 and colonic AGPAT1 are suggested possible PSC-UC biomarkers.
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13. |
- Wijk, Katarina, et al.
(author)
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Perceived enabling factors and barriers for the implementation of improvements in health care in order to achieve patient-centred care : A case report from Sweden
- 2020
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In: Journal of Evaluation In Clinical Practice. - : John Wiley & Sons. - 1356-1294 .- 1365-2753. ; 26:3, s. 791-800
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Journal article (peer-reviewed)abstract
- Abstract Rationale, aim, and objectives More knowledge is needed regarding the complex factors and perceptions that enable the implementation of change in health care. The study aimed to examine the enabling factors and barriers encountered in the implementation of improvements in health care in order to achieve patient-centred care (PCC) and to study if there was a correlation in the extent the improvements were perceived to be implemented and the preconditions that were considered to affect them. Methods Using a mixed method design, data were gathered via a questionnaire and individual interviews with health care personnel, clinic managers, and first-line managers. The data collection and analyses were based on the framework for Promoting Action on Research Implementation in Health Services (PARiHS). Correlations between PCC improvements and preconditions for improvements were performed. Results A high level of involvement, knowledge, and adequate resources were considered important to achieve an implementation of PCC with joint responsibility. Leadership and management need to be explicit and promote continuous follow-up and feedback. Preconditions for improvement had a linear correlation with the perceived level of implementation. Knowledge-related preconditions had greatest impact on implementation. Conclusions The PARiHS framework was appropriate to use since the three components of evidence, context, and facilitation present different important preconditions in the implementation process. Evidence was the highest rated contributor since evidence-based practices in health care are necessary. It is vital that the important role of the context and facilitators is acknowledged in the implementation process to enable a successful implementation of change. There is a need to incorporate a clear strategy involving all levels in the organization. Furthermore, leaders play an important role in the implementation by facilitating communication and support and by having trust in facilitators and health care personnel. The results are applicable to other interventions implementing change in health care.
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14. |
- Yrjänäinen, Väinö, et al.
(author)
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The Swedish parliament corpus 1867–2022
- 2024
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In: Proceedings of the 2024 Joint International Conference on Computational Linguistics, Language Resources and Evaluation (LREC-COLING 2024). - : ELRA Language Resource Association. - 9782493814104 ; , s. 16100-16112
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Conference paper (peer-reviewed)abstract
- The Swedish parliamentary records are an important source material for social science and humanities researchers. We introduce a new research corpus, the Swedish Parliament Corpus, which is larger and more developed than previously available research corpora for the Swedish parliament. The corpus contains annotated and structured parliamentary records over more than 150 years, through the bicameral parliament (1867–1970) and the unicameral parliament (1971–). In addition to the records, which contain all speeches in the parliament, we also provide a database of all members of parliament over the same period. Along with the corpus, we describe procedures to ensure data quality. The corpus facilitates detailed analysis of parliamentary speeches in several research fields.
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15. |
- Zhang, Huai, et al.
(author)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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In: Hepatology international. - 1936-0541.
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Journal article (peer-reviewed)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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16. |
- Zhao, Hongxing, et al.
(author)
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Detection of SARS-CoV-2 antibodies in serum and dried blood spot samples of vaccinated individuals using a sensitive homogeneous proximity extension assay.
- 2022
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In: New biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 72, s. 139-148
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Journal article (peer-reviewed)abstract
- A homogeneous PCR-based assay for sensitive and specific detection of antibodies in serum or dried blood spots (DBS) is presented and the method is used to monitor individuals infected with or vaccinated against SARS-CoV-2. Detection probes were prepared by conjugating the recombinant spike protein subunit 1 (S1), containing the receptor binding domain (RBD) of SARS-CoV-2, to each of a pair of specific oligonucleotides. The same was done for the nucleocapsid protein (NP). Upon incubation with serum or DBS samples, the bi- or multivalency of the antibodies (IgG, IgA or IgM) brings pairs of viral proteins with their conjugated oligonucleotides in proximity, allowing the antibodies to be detected by a modified proximity extension assay (PEA). Anti-S1 and anti-NP antibodies could be detected simultaneously from one incubation reaction. This Antibody PEA (AbPEA) test uses only 1µl of neat or up to 100,000-fold diluted serum or one ø1.2mm disc cut from a DBS. All 100 investigated sera and 21 DBS collected prior to the COVID-19 outbreak were negative, demonstrating a 100% specificity. The area under the curve, as evaluated by Receiver Operating Characteristic (ROC) analysis reached 0.998 (95%CI: 0.993-1) for samples taken from 11 days after symptoms onset. The kinetics of antibody responses were monitored after a first and second vaccination using serially collected DBS from 14 individuals. AbPEA offers highly specific and sensitive solution-phase antibody detection without requirement for secondary antibodies, no elution step when using DBS sample in a simple procedure that lends itself to multiplex survey of antibody responses.
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18. |
- Åberg, Anna Cristina, et al.
(author)
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Extraction of gait parameters from marker-free video recordings of Timed Up-and-Go tests : Validity, inter- and intra-rater reliability.
- 2021
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In: Gait & Posture. - : Elsevier. - 0966-6362 .- 1879-2219. ; 90, s. 489-495
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Journal article (peer-reviewed)abstract
- BACKGROUND: We study dual-task performance with marker-free video recordings of Timed Up-and-Go tests (TUG) and TUG combined with a cognitive/verbal task (TUG dual-task, TUGdt).RESEARCH QUESTION: Can gait parameters be accurately estimated from video-recorded TUG tests by a new semi-automatic method aided by a technique for human 2D pose estimation based on deep learning?METHODS: Thirty persons aged 60-85 years participated in the study, conducted in a laboratory environment. Data were collected by two synchronous video-cameras and a marker-based optoelectronic motion capture system as gold standard, to evaluate the gait parameters step length (SL), step width (SW), step duration (SD), single-stance duration (SSD) and double-stance duration (DSD). For reliability evaluations, data processing aided by a deep neural network model, involved three raters who conducted three repetitions of identifying anatomical keypoints in recordings of one randomly selected step from each of the participants. Validity was analysed using 95 % confidence intervals (CI) and p-values for method differences and Bland-Altman plots with limits of agreement. Inter- and intra-rater reliability were calculated as intraclass correlation coefficients (ICC) and standard errors of measurement. Smallest detectable change was calculated for inter-rater reliability.RESULTS: Mean ddifferences between video and the motion capture system data for SW, DSD, and SSD were significant (p < 0.001). However, mean differences for all parameters were small (-6.4%-13.0% of motion capture system) indicating good validity. Concerning reliability, almost all 95 % CI of the ICC estimates exceeded 0.90, indicating excellent reliability. Only inter-rater reliability for SW (95 % CI = 0.892;0.973) and one rater's intra-rater reliability for SSD (95 % CI = 0.793;0.951) were lower, but still showed good to excellent reliability.SIGNIFICANCE: The presented method for extraction of gait parameters from video appears suitable for valid and reliable quantification of gait. This opens up for analyses that may contribute to the knowledge of cognitive-motor interference in dual-task testing.
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19. |
- Åberg, Fredrik, et al.
(author)
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Everolimus and long-term decline in renal function after liver transplantation: real-life experience with measured GFR
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:6, s. 718-724
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Journal article (peer-reviewed)abstract
- Switching from calcineurin-inhibitors (CNI) to everolimus >6-12-months after liver transplantation (LT) seems inefficient in improving renal function, but whether everolimus halts further renal-function decline compared to low-dose CNI remains unclear. In a retrospective single-center study of everolimus after LT (2008-2016) with routine measured glomerular filtration rates (mGFR;Cr-51-EDTA- or iohexol clearance), we compared by propensity-score matching everolimus therapy to low-dose CNI therapy. The study comprised 36 patients with everolimus introduced on average 22 months post-LT (range 2-105 months, median follow-up 3.4 years), and 36 matched controls. Everolimus introduction was associated with a mean improvement in mGFR of 7 mL/min up to 1 year (p = .003), restricted to patients switched 5 ng/mL. The differences between the everolimus group and controls in delta-mGFR from baseline to 1 year (7.3 vs 4.3 mL/min,p = .25) or 1-year to last follow-up (-0.8 vs -0.2 mL/min/year,p = .71) were non-significant. Proportions with mGFR decline >3 mL/min/year were similar between groups (11% and 14%,p = 1.00). Everolimus was stopped in three patients (8%), and acute rejection occurred in 17%. In conclusion, despite an early improvement in renal function after everolimus introduction, we found no evidence that everolimus halts the long-term mGFR decline compared to continued low-dose CNI therapy. Due to retrospective design, small sample size and heterogenous characteristics, definite conclusions require prospective studies.
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