| 1. |
- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 4. |
- Kesteloot, N., et al.
(författare)
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Deformation and mixing of coexisting shapes in neutron-deficient polonium isotopes
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:5
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Tidskriftsartikel (refereegranskat)abstract
- Coulomb-excitation experiments are performed with postaccelerated beams of neutron-deficient Po-196,Po-198,Po-200,Po-202 isotopes at the REX-ISOLDE facility. A set of matrix elements, coupling the low-lying states in these isotopes, is extracted. In the two heaviest isotopes, Po-196,Po-198, the transitional and diagonal matrix elements of the 2(1)(+) state are determined. In Po-196,Po-198 multistep Coulomb excitation is observed, populating the 4(1)(+), 0(2)(+), and 2(2)(+) states. The experimental results are compared to the results from the measurement of mean-square charge radii in polonium isotopes, confirming the onset of deformation from Po-196 onwards. Three model descriptions are used to compare to the data. Calculations with the beyond-mean-field model, the interacting boson model, and the general Bohr Hamiltonian model show partial agreement with the experimental data. Finally, calculations with a phenomenological two-level mixing model hint at the mixing of a spherical structure with a weakly deformed rotational structure.
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| 9. |
- Logroscino, G, et al.
(författare)
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Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries
- 2023
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:3, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.ObjectiveTo assess the incidence of FTLD across Europe.Design, Setting, and ParticipantsThe Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and MeasuresRandom-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.ResultsBased on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and RelevanceThe findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.
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| 10. |
- Roger, T., et al.
(författare)
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Precise Determination of the Unperturbed B8 Neutrino Spectrum
- 2012
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Ingår i: Phys. Rev. Lett.. ; 108:16, s. Art. no. 162502-
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Tidskriftsartikel (refereegranskat)abstract
- A measurement of the final state distribution of the 8B beta decay, obtained by implanting a 8B beam in a double-sided silicon strip detector, is reported here. The present spectrum is consistent with a recent independent precise measurement performed by our collaboration at the IGISOL facility, Jyvaskyla [O. S.Kirsebom et al., Phys. Rev. C 83, 065802 (2011)]. It shows discrepancies with previously measuredspectra, leading to differences in the derived neutrino spectrum. Thanks to a low detection threshold, theneutrino spectrum is for the first time directly extracted from the measured final state distribution, thusavoiding the uncertainties related to the extrapolation of R-matrix fits. Combined with the IGISOL data,this leads to an improvement of the overall errors and the extension of the neutrino spectrum at highenergy. The new unperturbed neutrino spectrum represents a benchmark for future measurements of thesolar neutrino flux as a function of energy.
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| 11. |
- Wallin, Anders, 1950, et al.
(författare)
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Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.
- 2017
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 17:1
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Forskningsöversikt (refereegranskat)abstract
- Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested. In order to shed light in the current status on biochemical markers for VCI-SSVD, experts in field reviewed the recent evidence and literature data.The group conducted a comprehensive search on Medline, PubMed and Embase databases for studies published until 15.01.2017. The proposal on current status of biochemical markers in VCI-SSVD was reviewed by all co-authors and the draft was repeatedly circulated and discussed before it was finalized.This review identifies a large number of biochemical markers derived from CSF and blood. There is a considerable overlap of VCI-SSVD clinical symptoms with those of Alzheimer's disease (AD). Although most of the published studies are small and their findings remain to be replicated in larger cohorts, several biomarkers have shown promise in separating VCI-SSVD from AD. These promising biomarkers are closely linked to underlying SSVD pathophysiology, namely disruption of blood-CSF and blood-brain barriers (BCB-BBB) and breakdown of white matter myelinated fibres and extracellular matrix, as well as blood and brain inflammation. The leading biomarker candidates are: elevated CSF/blood albumin ratio, which reflects BCB/BBB disruption;altered CSF matrix metalloproteinases, reflecting extracellular matrix breakdown; CSF neurofilment as a marker of axonal damage, and possibly blood inflammatory cytokines and adhesion molecules. The suggested SSVD biomarker deviations contrasts the characteristic CSF profile in AD, i.e. depletion of amyloid beta peptide and increased phosphorylated and total tau.Combining SSVD and AD biomarkers may provide a powerful tool to identify with greater precision appropriate patients for clinical trials of more homogeneous dementia populations. Thereby, biomarkers might promote therapeutic progress not only in VCI-SSVD, but also in AD.
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| 13. |
- Fynbo, H. O. U., et al.
(författare)
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The β-decay approach for studying 12C
- 2008
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 111:1
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Tidskriftsartikel (refereegranskat)abstract
- The β-decays of the mirror nuclei 12B and 12N both populate states in 12C and they are therefore a precious source of information about this nucleus. Due to the selection rules of β-decay only 0+, 1+ and 2+ states are populated. This allows a very clean study of unbound states just above the 3α-threshold with those spin and parities. This probe has been applied in two experiments using two complementary experimental techniques: in the first the three α-particles emitted after β-decay are measured in coincidence in separate detectors using the ISOL method, while in the second method 12B and 12N are implanted in a detector and the summed energy of the three α-particles is measured directly. Preliminary results from the two approaches are presented. © 2008 IOP Publishing Ltd.
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| 14. |
- Hyldegaard, S., et al.
(författare)
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Precise branching ratios to unbound 12C states from 12N and 12B [beta]-decays
- 2009
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 678:5, s. 459 - 464
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Tidskriftsartikel (refereegranskat)abstract
- Two complementary experimental techniques have been used to extract precise branching ratios to unbound states in 12C from 12N and 12B [beta]-decays. In the first the three [alpha]-particles emitted after [beta]-decay are measured in coincidence in separate detectors, while in the second method 12N and 12B are implanted in a detector and the summed energy of the three [alpha]-particles is measured directly. For the narrow states at 7.654 MeV (0+) and 12.71 MeV (1+) the resulting branching ratios are both smaller than previous measurements by a factor of [similar, equals]2. The experimental results are compared to no-core shell model calculations with realistic interactions from chiral perturbation theory, and inclusion of three-nucleon forces is found to give improved agreement.
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| 15. |
- Hyldegaard, S., et al.
(författare)
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R-matrix analysis of the beta decays of 12N and 12B
- 2010
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 81:2
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Tidskriftsartikel (refereegranskat)abstract
- The β decays of 12N and 12B have been studied at KVI and JYFL to resolve the composition of the broad and interfering 0+ and 2+ strengths in the triple-α continuum. For the first time a complete treatment of 3α decay is presented including all major breakup channels. A multilevel, many-channel R-matrix formalism has been developed for the complete description of the breakup in combination with the recently published separate analysis of angular correlations. We find that, in addition to the Hoyle state at 7.65 MeV, more than one 0+ and 2+ state is needed to reproduce the spectra. Broad 03+ and 22+ states are found between 10.5 and 12 MeV in this work. The presence of β strength up to the 12N Q-value window suggests the presence of additional 0+ and 2+ components in the 12C structure at energies above 12.7 MeV.
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| 16. |
- Hyldegaard, S., et al.
(författare)
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STUDIES OF C-12 USING beta-DECAYS
- 2008
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Ingår i: International Journal of Modern Physics E. - 0218-3013. ; 17:10, s. 2182-2187
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Konferensbidrag (refereegranskat)abstract
- The nuclear structure of states in C-12 have been a subject of interest for both theory and experiment since the early days of nuclear physics. Many open questions remain, especially concerning the existence and properties of 0(+) and 2(+) states in the triple alpha continuum. A series of experiments have been performed using beta-decay of N-12 and B-12 to probe these states. The latest experiment was performed at KVI using an implantation method, measuring the sum energy of the three alpha-particles directly. Preliminary results from this experiment will be presented.
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| 19. |
- Traykov, Vassil, et al.
(författare)
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Clinical practice and implementation of guidelines for the prevention, diagnosis and management of cardiac implantable electronic device infections : results of a worldwide survey under the auspices of the European Heart Rhythm Association
- 2019
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 21:8, s. 1270-1279
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Cardiac implantable electronic device (CIED) infection rates are increasing. Worldwide compliance and disparities to published guidelines for the prevention, diagnosis and management of these conditions are not well elucidated. The purpose of this survey, therefore, was to clarify these issues through an inquiry to arrhythmia-related associations and societies worldwide.METHODS AND RESULTS: A questionnaire comprising 15 questions related to CIED infections was distributed among members of seven arrhythmia societies worldwide. A total of 234 centres in 62 countries reported implantation rates of which 159 (68.0%) performed more than 200 device implantations per year and 14 (6.0%) performed fewer than 50 implantations per year. The reported rates of CIED infections for 2017 were ≤2% in 78.7% of the centres, while the infection rates exceeded 5% in 7.8% of the centres. Preventive measures for CIED infection differed from published recommendations and varied among different regions mainly in terms of pocket irrigation and administering post-operative antimicrobial therapy the use of which was reported by 39.9% and 44% of the respondents, respectively. Antibacterial envelopes were used by 37.7% of the respondents in selected circumstances. In terms of pocket infection management, 62% of the respondents applied complete system removal as an initial step. Diagnostic pocket needle aspiration and pocket surgical debridement were reported by 15.8% and 11.8% of centres, respectively.CONCLUSION: Clinical practices for prevention and management of CIED do not fully comply with current recommendations and demonstrate considerable regional disparities. Further education and programmes for improved implementation of guidelines are mandatory.
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