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Bylting í þróun bóluefna
(2021-03) Jónsdóttir, Ingileif; Læknadeild
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Genetic insight into sick sinus syndrome
(2021-02-13) DBDS Genomic Consortium; Faculty of Medicine; Faculty of Industrial Engineering, Mechanical Engineering and Computer Science; Health Sciences
Aims: The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results: We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). Conclusion: We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
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Predicting the probability of death using proteomics
(2021-06-18) Eiriksdottir, Thjodbjorg; Ardal, Steinthor; Jonsson, Benedikt A.; Lund, Sigrun H.; Ivarsdottir, Erna V.; Norland, Kristjan; Ferkingstad, Egil; Stefansson, Hreinn; Jónsdóttir, Ingileif; Holm, Hilma; Rafnar, Thorunn; Saemundsdottir, Jona; Norddahl, Gudmundur L.; Þorgeirsson, Guðmundur; Gudbjartsson, Daniel F.; Sulem, Patrick; Thorsteinsdottir, Unnur; Stefansson, Kari; Úlfarsson, Magnús Örn; Faculty of Physical Sciences; Faculty of Medicine; Faculty of Electrical and Computer Engineering; Health Sciences
Predicting all-cause mortality risk is challenging and requires extensive medical data. Recently, large-scale proteomics datasets have proven useful for predicting health-related outcomes. Here, we use measurements of levels of 4,684 plasma proteins in 22,913 Icelanders to develop all-cause mortality predictors both for short- and long-term risk. The participants were 18-101 years old with a mean follow up of 13.7 (sd. 4.7) years. During the study period, 7,061 participants died. Our proposed predictor outperformed, in survival prediction, a predictor based on conventional mortality risk factors. We could identify the 5% at highest risk in a group of 60-80 years old, where 88% died within ten years and 5% at the lowest risk where only 1% died. Furthermore, the predicted risk of death correlates with measures of frailty in an independent dataset. Our results show that the plasma proteome can be used to assess general health and estimate the risk of death.
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Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis
(2022-01) Harðardóttir, Hrönn; Aspelund, Thor; Zhu, Jianwei; Fall, Katja; Hauksdóttir, Arna; Fang, Fang; Lu, Donghao; Janson, Christer; Jónsson, Steinn; Valdimarsdóttir, Heiðdís; Valdimarsdóttir, Unnur Anna; Hardardottir, Hronn; Faculty of Medicine
Purpose: The aim of this study was to assess the role of the patient’s background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. Methods: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. Results: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (β = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (β = 8.8, 95% CI: 2.7 to 14.9), while high educational level (β = − 7.9, 95% CI: − 14.8 to − 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients’ perception of optimal doctor-patient (β = − 9.1, 95% CI: − 14.9 to − 3.3) and family communication (β = − 8.6, 95% CI: − 14.3 to − 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. Conclusions: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms.
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Exploring preservice, beginning and experienced teachers' noticing of classroom management situations from an actor's perspective
(2021-10-01) van Driel, Sharisse; Crasborn, Frank; Wolff, Charlotte E.; Brand-Gruwel, Saskia; Jarodzka, Halszka; Faculty of Subject Teacher Education
We investigated preservice (n = 21), beginning (n = 17) and experienced (n = 19) teachers' noticing of salient classroom management situations during teaching. Teachers wore a front-view camera while teaching. A two-method approach was used to identify salient situations and verbalizations of accompanying cognitions: hand-signals while teaching and stimulated-recall interview. Mixed-method analysis showed that teacher groups noticed similar amounts and types of situations distributed across the lesson time. Preservice teachers identified more situations than beginners in interviews, whereas beginners identified more situations by hand-signaling while teaching. Findings indicate non-linear professional development of teachers' noticing and the value of a two-method approach to capture teachers’ noticing.