| 1. |
- Klaric, Lucija, et al.
(författare)
-
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
|
|
| 2. |
- Månsson, Jonas, 1964-, et al.
(författare)
-
Metoder för att utvärdera den regionala tillväxtpolitiken Lärdomar och råd för utvärderare och uppdragsgivare
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här rapporten beskriver olika metoder och angreppssätt för att utvärdera den regionalatillväxtpolitiken. Rapporten utgör slutrapport för ITPS regleringsbrevsuppdrag nummer 6,2008. Målgruppen för rapporten är utvärderare samt beställare av utvärderingar.Rapporten består av ett teorikapitel samt fem kapitel med fem olika metoder ellerangreppssätt speciellt lämpliga för utvärderingar av den regionala tillväxtpolitiken.Utvärderingar är i allmänhet inriktade mot att antingen studerautfallet eller genomförandetav en åtgärd. Utvärderingar som studerar utfallet delas in i mål-, effekt- ocheffektivitetsutvärderingar. En målutvärdering svarar på frågan om målen har uppfyllts; eneffektutvärdering om måluppfyllelsen är en effekt av åtgärden; en effektivitetsutvärderingom de uppnådda effekterna värderas högre än kostnaderna för åtgärden, medan slutligen engenomförandeutvärdering besvarar frågan om hur själva genomförandet kan ha påverkatmåluppfyllelse, effekt eller effektivitet. En utfallsutvärdering kan med fördel kombinerasmed en genomförandeutvärdering, eftersom den senare kan vara till hjälp att tolkautfallsutvärderingens resultat.Utvärderingar av åtgärder inom den regionala tillväxtpolitiken bör ta särskild hänsyn tillden regionala heterogeniteten. Rapporten ger därför rekommendationer beträffandeanvändandet av regionala indikatorer samt rörande en statistisk metod – flernivåanalys.Indikatorer och flernivåanalys är båda användbara verktyg för att ta hänsyn till denregionala heterogeniteten.En viktig aspekt i utvärderingssammanhang är att kvalitetssäkra arbetet med utvärderingar.Rapporten ger därför även rekommendationer som avser utnyttjandet av ”metautvärdering”som metod för sådan kvalitetssäkring. Metautvärderingar är en bra metod för attkvalitetssäkra arbetet med utvärdering av program eftersom metoden innefattar ett tydligtlärandeperspektiv så att misstag inte upprepas.Tillförlitliga och användbara utvärderingar förutsätter en välgjord datainsamling avåtgärdens utfall, samt en dokumentation av genomförandet. En adekvat datainsamlingförutsätter att de individer, företag osv. vilka åtgärden gäller, kan identifieras och följasöver tid. Om inte nödvändig information finns i befintliga register, kan data behöva samlasin redan innan åtgärden har implementerats. Ett sätt att minska risken för svårutvärderadeåtgärder är att utvärderaren kopplas in tidigt i processen för att garantera dokumentationenoch därmed även utvärderbarheten.Då åtgärdsprogram går mot att bli allt mer komplexa, med många olika aktörer ochmålgrupper, beskriver även rapporten olika angreppssätt för att utvärdera komplexaprogram och horisontell samverkan. Att utvärdera sådana program kräver en öppenhet motnya metoder, samt en kombination av både kvalitativa och kvantitativa metoder.
|
|
| 3. |
- Ulmefors, Hanna, et al.
(författare)
-
Solution-Spinning of a Collection of Micro- and Nanocarrier-Functionalized Polysaccharide Fibers
- 2022
-
Ingår i: Macromolecular materials and engineering. - : John Wiley and Sons Inc. - 1438-7492 .- 1439-2054. ; 307:8
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous polysaccharide fibers and nonwovens—based on cellulose, hydroxypropyl cellulose, chitosan, or alginate—containing biopolymeric microcapsules (MC) or mesoporous silica nanoparticles (MSN) are prepared using a wet-spinning or solution blowing technique. The MCs are homogeneously distributed in the fiber matrices whereas the MSNs form discrete micron-sized aggregates as demonstrated using scanning electron-, fluorescence-, and confocal microscopy. By encapsulating the model compound pyrene, it is shown that 95% of the substance remains in the fiber during the formation process as compared to only 7% for the nonencapsulated substance. The material comprising the MC has a strong impact on the release behavior of the encapsulated pyrene as investigated using methanol extraction. MCs based on poly(l-lactic acid) prove to be practically impermeable with no pyrene released in contrast to MCs based on poly(lactic-co-glycolic acid) which allow for diffusion of pyrene through the MC and fiber as visualized using fluorescence microscopy. © 2022 The Authors.
|
|
| 4. |
- Wahlander, K, et al.
(författare)
-
Pharmacokinetics, pharmacodynamics and clinical effects of the oral direct thrombin inhibitor ximelagatran in acute treatment of patients with pulmonary embolism and deep vein thrombosis
- 2002
-
Ingår i: Thrombosis Research. - 1879-2472. ; 107:3-4, s. 93-99
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6-9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after administration of ximelagatran. Melagatran plasma concentration profiles were similar on Days 1, 2, and 6-9. Plasma activated partial thromboplastin time increased following administration of ximelagatran and reached a peak that was approximately twofold higher than the predose activated partial thromboplastin time and correlated with melagatran plasma concentrations (R-2 = 0.69). All but one patient (with malignancy) showed regressed or unchanged lung scintigraphic findings, and six of these demonstrated no, or only minor, perfusion defects at central evaluation after 6-9 days of ximelagatran treatment. Clinical symptoms, including chest pain, dyspnoea, cough, and oedema, and pain in the affected leg, were improved. Ximelagatran was well tolerated with no deaths or severe bleeding events reported during treatment. Conclusion: Treatment with a fixed dose of oral ximelagatran, used without routine coagulation monitoring, showed reproducible pharmacokinetics and pharmacodynamics with a rapid onset of action and promising clinical results in patients with pulmonary embolism.
|
|
| 5. |
|
|
| 6. |
- Alexandersson, Elin, et al.
(författare)
-
Extended automated quantification algorithm (AQuA) for targeted 1H NMR metabolomics of highly complex samples: application to plant root exudates
- 2023
-
Ingår i: Metabolomics. - 1573-3882 .- 1573-3890. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The Automated Quantification Algorithm (AQuA) is a rapid and efficient method for targeted NMR-based metabolomics, currently optimised for blood plasma. AQuA quantifies metabolites from 1D-H-1 NMR spectra based on the height of only one signal per metabolite, which minimises the computational time and workload of the method without compromising the quantification accuracy.Objectives To develop a fast and computationally efficient extension of AQuA for quantification of selected metabolites in highly complex samples, with minimal prior sample preparation. In particular, the method should be capable of handling interferences caused by broad background signals.Methods An automatic baseline correction function was combined with AQuA into an automated workflow, the extended AQuA, for quantification of metabolites in plant root exudate NMR spectra that contained broad background signals and baseline distortions. The approach was evaluated using simulations as well as a spike-in experiment in which known metabolite amounts were added to a complex sample matrix.Results The extended AQuA enables accurate quantification of metabolites in 1D-H-1 NMR spectra with varying complexity. The method is very fast (< 1 s per spectrum) and can be fully automated.Conclusions The extended AQuA is an automated quantification method intended for 1D-H-1 NMR spectra containing broad background signals and baseline distortions. Although the method was developed for plant root exudates, it should be readily applicable to any NMR spectra displaying similar issues as it is purely computational and applied to NMR spectra post-acquisition.
|
|
| 7. |
- Andersson, Daniel P., et al.
(författare)
-
Relation among hypertriglyceridaemia, cardiometabolic disease, and hereditary factors : design and rationale of the Stockholm hyperTRIglyceridaemia REGister study
- 2024
-
Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 4:2
-
Tidskriftsartikel (refereegranskat)abstract
- AimsHypertriglyceridaemia (hTG) is associated with atherosclerotic cardiovascular disease, pancreatitis, and non-alcoholic fatty liver disease (NAFLD) in large population-based studies. The understanding of the impact of hereditary hTG and cardiometabolic disease status on the development of hTG and its associated cardiometabolic outcomes is more limited. We aimed to establish a multigenerational cohort to enable studies of the relationship between hTG, cardiometabolic disease and hereditary factors.Methods and resultsThe population-based observational Stockholm hyperTRIglyceridaemia REGister (STRIREG) study includes 1 460 184 index individuals who have measured plasma triglycerides in the clinical routine in Region Stockholm, Sweden, between 1 January 2000 and 31 December 2021. The laboratory measurements also included basic haematology, blood lipid panel, liver function tests, and HbA1c. Using the Swedish Multi-Generation register, 2 147 635 parents and siblings to the indexes were identified to form the complete study cohort. Laboratory data from participants were combined with data from several national registers that provided information on the cause of death, medical diagnoses, dispensed medicines, and socioeconomic factors including country of birth, education level, and marital status.ConclusionThe multi-generational longitudinal STRIREG cohort provides a unique opportunity to investigate different aspects of hTG as well as heredity for other metabolic diseases. Important outcome measures include mortality, cardiovascular mortality, major cardiovascular events, development of incident diabetes, and NAFLD. The STRIREG study will provide a deeper understanding of the impact of hereditary factors and associated cardiometabolic complications.
|
|
| 8. |
- Andersson, Per, et al.
(författare)
-
Anger and disgust shape judgments of social sanctions across cultures, especially in high individual autonomy societies
- 2024
-
Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.
|
|
| 9. |
- Arfvidsson, Gustav Frisk, et al.
(författare)
-
Design Considerations for Short Alerts and Notification Sounds in a Retail Environment
- 2021
-
Ingår i: Proceedings of the Sound and Music Computing Conferences. - : Sound and Music Computing Network. - 9788894541540 ; , s. 261-267
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The design and noticeability of alert sounds have been widely researched and reported, and not least, notification sounds are ubiquitous in both software and hardware product development. In an ongoing research project concerning the retail industry, we aim at designing short alert sounds that only grab attention from one group of customers, while others do not register the alerts: this particular aspect has to our knowledge not yet been studied. To establish design guidelines for such alert sounds, we conducted an experiment where test subjects would experience ordinary shopping activity including background music and an ambient soundscape in a virtual reality clothing store, but with added alert sounds. We tested, specifically, six differently designed sound alerts belonging to two classes: contextual-specific congruent sounds, and incongruent sounds that did not fit the sonic context. The results disproved our assumptions that incongruent sounds would outperform the congruent and thus in the context more anticipated sounds. The findings suggest that alert sounds can be designed with subtlety and still be noticeable and that customers will not necessarily be annoyed. We present here a first approach towards design guidelines for short alert sounds in a shop environment. Copyright: © 2021 the Authors.
|
|
| 10. |
|
|
