| 1. |
- Erhardt, Tobias, et al.
(författare)
-
High-resolution aerosol concentration data from the Greenland NorthGRIP and NEEM deep ice cores
- 2022
-
Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:3, s. 1215-1231
-
Tidskriftsartikel (refereegranskat)abstract
- Records of chemical impurities from ice cores enable us to reconstruct the past deposition of aerosols onto polar ice sheets and alpine glaciers. Through this they allow us to gain insight into changes of the source, transport and deposition processes that ultimately determine the deposition flux at the coring location. However, the low concentrations of the aerosol species in the ice and the resulting high risk of contamination pose a formidable analytical challenge, especially if long, continuous and highly resolved records are needed. Continuous flow analysis, CFA, the continuous melting, decontamination and analysis of ice-core samples has mostly overcome this issue and has quickly become the de facto standard to obtain high-resolution aerosol records from ice cores after its inception at the University of Bern in the mid-1990s.Here, we present continuous records of calcium (Ca2+), sodium (Na+), ammonium (NH+4), nitrate (NO-3) and electrolytic conductivity at 1 mm depth resolution from the NGRIP (North Greenland Ice Core Project) and NEEM (North Greenland Eemian Ice Drilling) ice cores produced by the Bern Continuous Flow Analysis group in the years 2000 to 2011 (Erhardt et al., 2021). Both of the records were previously used in a number of studies but were never published in full 1 mm resolution. Alongside the 1 mm datasets we provide decadal averages, a detailed description of the methods, relevant references, an assessment of the quality of the data and its usable resolution. Along the way we will also give some historical context on the development of the Bern CFA system.
|
|
| 2. |
- Allentoft, Morten E., et al.
(författare)
-
100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
|
|
| 3. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 4. |
- Glinge, Charlotte, et al.
(författare)
-
Familial clustering of unexplained heart failure – A Danish nationwide cohort study
-
Ingår i: International Journal of Cardiology. - 0167-5273.
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF. Methods and results: Using Danish nationwide registry data (1978–2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29–2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69–9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40–9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75–10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90–19.49]. Conclusion: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.
|
|
| 5. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 6. |
- Kjær, Kurt H., et al.
(författare)
-
Glacier response to the Little Ice Age during the Neoglacial cooling in Greenland
- 2022
-
Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 227
-
Tidskriftsartikel (refereegranskat)abstract
- In the Northern Hemisphere, an insolation driven Early to Middle Holocene Thermal Maximum was followed by a Neoglacial cooling that culminated during the Little Ice Age (LIA). Here, we review the glacier response to this Neoglacial cooling in Greenland. Changes in the ice margins of outlet glaciers from the Greenland Ice Sheet as well as local glaciers and ice caps are synthesized Greenland-wide. In addition, we compare temperature reconstructions from ice cores, elevation changes of the ice sheet across Greenland and oceanographic reconstructions from marine sediment cores over the past 5,000 years. The data are derived from a comprehensive review of the literature supplemented with unpublished reports. Our review provides a synthesis of the sensitivity of the Greenland ice margins and their variability, which is critical to understanding how Neoglacial glacier activity was interrupted by the current anthropogenic warming. We have reconstructed three distinct periods of glacier expansion from our compilation: two older Neoglacial advances at 2,500 – 1,700 yrs. BP (Before Present = 1950 CE, Common Era) and 1,250 – 950 yrs. BP; followed by a general advance during the younger Neoglacial between 700-50 yrs. BP, which represents the LIA. There is still insufficient data to outline the detailed spatio-temporal relationships between these periods of glacier expansion. Many glaciers advanced early in the Neoglacial and persisted in close proximity to their present-day position until the end of the LIA. Thus, the LIA response to Northern Hemisphere cooling must be seen within the wider context of the entire Neoglacial period of the past 5,000 years. Ice expansion appears to be closely linked to changes in ice sheet elevation, accumulation, and temperature as well as surface-water cooling in the surrounding oceans. At least for the two youngest Neoglacial advances, volcanic forcing triggering a sea-ice /ocean feedback, could explain their initiation. There are probably several LIA glacier fluctuations since the first culmination close to 1250 CE (Common Era) and available data suggests ice culminations in the 1400s, early to mid-1700s and early to mid-1800s CE. The last LIA maxima lasted until the present deglaciation commenced around 50 yrs. BP (1900 CE). The constraints provided here on the timing and magnitude of LIA glacier fluctuations delivers a more realistic background validation for modelling future ice sheet stability.
|
|
| 7. |
- Kjær, Louise Binow, et al.
(författare)
-
‘Making room for student autonomy’ – an ethnographic study of student participation in clinical work
- 2022
-
Ingår i: Advances in Health Sciences Education. - : Springer Science and Business Media LLC. - 1382-4996 .- 1573-1677. ; 27:4, s. 1067-1094
-
Tidskriftsartikel (refereegranskat)abstract
- Participation in clinical work is important for medical students’ professional development. However, students often report that they experience a passive observer role, and further research on contextual factors that influence student participation is needed. The theory of practice architectures contributes a new perspective to this challenge by elucidating how cultural-discursive, material-economic, and social-political arrangements enable and constrain student participation in clinical work. The aim of this study was to explore how practice architectures in clinical learning environments enable and constrain medical students’ participation. The study was designed as an ethnographic field study in three student clinics: 106 h of observation. Analysis comprised ethnographic analysis followed by application of the theory of practice architectures. The ethnographic analysis resulted in six themes: setting the scene, when to call for help, my room – my patient, getting in a routine, I know something you don’t, and my work is needed. Applying the theory of practice architectures showed that material-economic arrangements, such as control of the consultation room and essential artefacts, were crucial to student participation and position in the clinical workplace. Furthermore, co-production of a student mandate to independently perform certain parts of a consultation enabled a co-productive student position in the hierarchy of care-producers. The findings offer a conceptually generalisable model for the study of material and social dimensions of clinical learning environments. Although not all clinical learning environments may wish to or have the resources to implement a student clinic, the findings offer insights into general issues about the arrangements of student participation relevant to most clinical teaching contexts.
|
|
| 8. |
- Kjær, Louise Binow, et al.
(författare)
-
Patient-centred learning in practice. A mixed methods study of supervision and learning in student clinics
- 2023
-
Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991. ; 112
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Patient-centred learning (PCL) allows medical students to practice a patient-centred approach; however, didactic characteristics of PCL have yet to be fully elucidated. Clinical placements structured as a student clinic (SC) enable authentic student-patient learning relations through enhanced student responsibility and can serve as examples of PCL. We explored the didactic characteristics of supervision and learning in SCs to provide recommendations for PCL-oriented medical education. Methods: Triangulation mixed methods study based on qualitative data collected from in-depth interviews with clinical teachers and quantitative data collected from student evaluations of supervision and learning in the SCs. Results: Supervision and learning in SCs were characterized by 1) a focus on student-patient compatibility and patient needs and resources, which indicated PCL, 2) person-centred explorative supervision to adjust challenges to students’ needs and resources, and 3) support of student autonomy to take responsibility for patient treatment. Conclusion: PCL was facilitated by clinical teachers through a dual person-centred didactic approach combined with autonomy-supportive didactic practice. This enabled the integration of patients’ and students’ needs and resources in clinical teaching. Practice implications: Clinical teachers can stimulate student-patient learning relations by selecting patients, exploring students’ needs and resources, and supporting student autonomy through reflective practice and backup.
|
|
| 9. |
|
|
| 10. |
- Mortensen, Camilla Bekker, et al.
(författare)
-
Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium
- 2024
-
Ingår i: Intensive Care Medicine. - 0342-4642. ; 50:1, s. 103-113
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of − 6.4%-points (95% confidence interval [CI] − 12.8%-points to − 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI − 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI − 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.
|
|
| 11. |
- Sondergaard, Mads T., et al.
(författare)
-
Calmodulin mutations causing catecholaminergic polymorphic ventricular tachycardia confer opposing functional and biophysical molecular changes
- 2015
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; 282:4, s. 803-816
-
Tidskriftsartikel (refereegranskat)abstract
- Calmodulin (CaM) is the central mediator of intracellular Ca2+ signalling in cardiomyocytes, where it conveys the intricate Ca2+ transients to the proteins controlling cardiac contraction. We recently linked two separate mutations in CaM (N53I and N97S) to dominantly inherited catecholaminergic polymorphic ventricular tachycardia (CPVT), an arrhythmic disorder in which exercise or acute emotion can lead to syncope and sudden cardiac death. Given the ubiquitous presence of CaM in all eukaryote cells, it is particular intriguing that carriers of either mutation show no additional symptoms. Here, we investigated the effects of the CaM CPVT mutations in a zebrafish animal model. Three-day-old embryos injected with either CaM mRNA showed no detectable pathologies or developmental abnormalities. However, embryos injected with CPVT CaM mRNA displayed increased heart rate compared to wild-type CaM mRNA under -adrenergic stimulation, demonstrating a conserved dominant cardiac specific effect between zebrafish and human carriers of these mutations. Motivated by the highly similar physiological phenotypes, we compared the effects of the N53I and N97S mutations on the biophysical and functional properties of CaM. Surprisingly, the mutations have opposing effects on CaM C-lobe Ca2+ binding affinity and kinetics, and changes to the CaM N-lobe Ca2+ binding are minor and specific to the N53I mutation. Furthermore, both mutations induce differential perturbations to structure and stability towards unfolding. Our results suggest different molecular disease mechanisms for the CPVT (N53I and N97S mutations) and strongly support that cardiac contraction is the physiological process most sensitive to CaM integrity.
|
|
