| 1. |
- Bergman, Peter, et al.
(författare)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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| 2. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 3. |
- Kirvalidze, Mariam, et al.
(författare)
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Effectiveness of integrated person-centered interventions for older people's care: Review of Swedish experiences and experts’ perspective
- 2024
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 295:6, s. 804-824
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Tidskriftsartikel (refereegranskat)abstract
- Older adults have multiple medical and social care needs, requiring a shift toward an integrated person-centered model of care. Our objective was to describe and summarize Swedish experiences of integrated person-centered care by reviewing studies published between 2000 and 2023, and to identify the main challenges and scientific gaps through expert discussions. Seventy-three publications were identified by searching MEDLINE and contacting experts. Interventions were categorized using two World Health Organization frameworks: (1) Integrated Care for Older People (ICOPE), and (2) Integrated People-Centered Health Services (IPCHS). The included 73 publications were derived from 31 unique and heterogeneous interventions pertaining mainly to the micro- and meso-levels. Among publications measuring mortality, 15% were effective. Subjective health outcomes showed improvement in 24% of publications, morbidity outcomes in 42%, disability outcomes in 48%, and service utilization outcomes in 58%. Workshop discussions in Stockholm (Sweden), March 2023, were recorded, transcribed, and summarized. Experts emphasized: (1) lack of rigorous evaluation methods, (2) need for participatory designs, (3) scarcity of macro-level interventions, and (4) importance of transitioning from person- to people-centered integrated care. These challenges could explain the unexpected weak beneficial effects of the interventions on health outcomes, whereas service utilization outcomes were more positively impacted. Finally, we derived a list of recommendations, including the need to engage care organizations in interventions from their inception and to leverage researchers’ scientific expertise. Although this review provides a comprehensive snapshot of interventions in the context of Sweden, the findings offer transferable perspectives on the real-world challenges encountered in this field.
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| 4. |
- Nilsson, Sigrid, 1997-
(författare)
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Vasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The menopausal transition is, for most women, accompanied by hot flushes and night sweats (i.e., vasomotor symptoms, VMS). VMS has been associated with a worsened cardiovascular risk profile, but whether VMS constitutes an independent risk marker for developing subclinical atherosclerotic cardiovascular disease (ASCVD) is still uncertain. Visceral adipose tissue (VAT) contributes more to systemic low-grade inflammation than abdominal subcutaneous adipose tissue (ASAT), enhancing atherosclerosis development. Physical activity is an effective behavioral strategy to maintain and improve cardiovascular health. Whether a resistance training intervention (RTI) could reduce low-grade inflammation and VAT volume in postmenopausal women with VMS remains unclear, and whether the RTI-associated effects could be maintained over time requires further investigation.Material and Methods: This thesis is based on three studies. Study 1 was conducted on a subset of participants from the cross-sectional population-based Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-64 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive female-specific questionnaire. VMS was assessed on a 4-point scale. Subclinical ASCVD was detected via coronary computed tomography angiography (CCTA), computed tomography (CT), and carotid ultrasound. Study 2 is a sub-study of 65 postmenopausal women with VMS and low physical activity, randomized to either three days/week of an RTI or unchanged physical activity for 15 weeks. Women underwent anthropometric measurements, magnetic resonance imaging (MRI), and blood sampling at baseline and after 15 weeks. During the last followup contact in Study 2 after two years, 35 women agreed to attend an additional clinic visit to reevaluate cardiovascular risk markers, marking the inception of Study 3.Results: Of 2995 women included in Study 1, 14.2% reported severe VMS (n = 425), 18.1% moderate VMS (n = 543), and 67.7% no or mild VMS (n = 2027). Current or previous severe VMS, but not moderate VMS, was significantly associated with CCTA-detected coronary atherosclerosis, with odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association was only present for >5 years durations of severe VMS or when the onset of severe VMS occurred before menopause. Adjustment for menopausal hormone therapy strengthened the association for women with severe VMS >5 years (OR 1.67, 95% CI 1.16 – 2.40). Women compliant with an RTI had compared to a control group (CG), decreased adiponectin (p < 0.01), ASAT (p < 0.01), VAT (p < 0.01), total abdominal adipose tissue (TAAT) (p < 0.01) and fat ratio (p <0.001). Furthermore, an RTI reduced moderate to severe VMS frequency to six months post-intervention compared to a CG, but did neither contribute to preserved cardiovascular health markers nor improved health-related quality of life (HRQoL) after two years compared to a CG.Conclusions: There is a need for extra vigilance regarding cardiovascular risk factors in the group of women suffering from severe VMS. Implementing a 15-week RTI in these women could counteract the VAT redistribution and alter the frequency of moderate to severe VMS with maintained effects up to six months.
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| 5. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 6. |
- Alkharaan, Hassan, et al.
(författare)
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Persisting Salivary IgG Against SARS-CoV-2 at 9 Months After Mild COVID-19 : A Complementary Approach to Population Surveys
- 2021
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 224:3, s. 407-414
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Tidskriftsartikel (refereegranskat)abstract
- Background. Declining humoral immunity in coronavirus disease 2019 (COVID-19) patients and possible reinfection have raised concern. Mucosal immunity, particularly salivary antibodies, may be short lived although long-term studies are lacking. Methods. Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n = 74, cohort 1), undiagnosed individuals with self-reported questionnaires (n = 147, cohort 2), and individuals sampled prepandemic (n = 35, cohort 3). Results. Salivary IgG antibody responses in cohort 1 (mainly mild COVID-19) were detectable up to 9 months postrecovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in blood and saliva in most patients. Salivary IgA was rarely detected at this time point. In cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19-like symptoms. Salivary IgG tolerated temperature and detergent pretreatments. Conclusions. Unlike SARS-CoV-2 salivary IgA that appeared short lived, specific saliva IgG appeared stable even after mild COVID-19, as for blood serology. This noninvasive saliva-based SARS-CoV-2 antibody test with home self-collection may be a complementary alternative to conventional blood serology.
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| 7. |
- Fagerberg, Linn, et al.
(författare)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Tidskriftsartikel (refereegranskat)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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| 8. |
- Loza, M. J., et al.
(författare)
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Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study
- 2016
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods: Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results: Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions: Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration:NCT01274507(ADEPT), registered October 28, 2010 and NCT01982162(U-BIOPRED), registered October 30, 2013.
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| 9. |
- Wastesson, Karin, et al.
(författare)
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Conditions for Workplace Learning as a New First-Line Manager in Elderly Care
- 2021
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Ingår i: Vocations and Learning. - : Springer. - 1874-785X .- 1874-7868. ; 14:2, s. 205-222
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this article is to explore first-line managers’ experiences of workplace learning in elderly care, with a particular focus on the conditions for learning when entering a new workplace as the new manager. Qualitative interviews were conducted with 35 first-line managers from three organisations in Sweden. Four learning conditions emerged as being particularly significant for first-line managers: the managers’ previous professional experience, job-specific training, social support, and the joint repertoire of organisational arrangements. These conditions shifted in importance during the process of entering the workplace, and the way in which the conditions gave access to learning for different managers varied. The managers’ professional experience and others’ recognition of them had a considerable impact on their admittance to the new workplace. After the initial entry phase, the other three learning conditions became more significant and played a role in enabling or constraining the managers’ learning and becoming the new manager. One conclusion is that contextual and work experiences from elderly care were significant for learning during the initial phase and in order to gain access to workplace learning. Another conclusion is that high expectations and great responsibility were placed on the managers to satisfy their own learning needs. This implies that professional, social and emotional support that is received informally is just as significant for learning as formalised training for entering a new workplace as a new manager.
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| 10. |
- Wastesson, Karin, et al.
(författare)
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First-line managers’ practices and learning in unpredictable work within elderly care
- 2022
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Ingår i: Studies in Continuing Education. - : Routledge. - 0158-037X .- 1470-126X. ; 44:3, s. 376-391
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Tidskriftsartikel (refereegranskat)abstract
- Despite the number of studies confirming a high degree of unpredictability in managerial work, little is still known about how managers? workplace learning happens within organisations in such circumstances. This paper therefore aims to contribute knowledge about managers? learning in managerial practice when work is unpredictable, by investigating how first-line managers deal with unforeseen situations and how they learn in such circumstances in everyday work. Data was collected via qualitative interviews with 40 first-line managers in Swedish elderly care. By using a theoretical framework based on practice and workplace learning theories, the paper analyses how managers address unpredictability in work through three embedded practices: maintaining, modifying and inventing. The paper goes beyond research on leadership training and leadership development by contributing knowledge about the everyday learning of first-line managers when their work is unpredictable. The unpredictable managerial work does not always create chaos; instead, there are very orderly ways of learning from dealing with unforeseen situations. The unforeseen is not as unpredictable as it might seem in managerial work. On the other hand, that which is not yet known calls for an inventing practice, which results in managers learning to take new paths that can create new practices.
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