| 1. |
- de Jong, R. S., et al.
(författare)
-
4MOST : Project overview and information for the First Call for Proposals
- 2019
-
Ingår i: The Messenger. - : European Southern Observatory. - 0722-6691. ; 175, s. 3-11
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We introduce the 4-metre Multi-Object Spectroscopic Telescope (4MOST), a new high-multiplex, wide-field spectroscopic survey facility under development for the four-metre-class Visible and Infrared Survey Telescope for Astronomy (VISTA) at Paranal. Its key specifications are: a large field of view (FoV) of 4.2 square degrees and a high multiplex capability, with 1624 fibres feeding two low-resolution spectrographs (R = λ/Δλ ~ 6500), and 812 fibres transferring light to the high-resolution spectrograph (R ~ 20 000). After a description of the instrument and its expected performance, a short overview is given of its operational scheme and planned 4MOST Consortium science; these aspects are covered in more detail in other articles in this edition of The Messenger. Finally, the processes, schedules, and policies concerning the selection of ESO Community Surveys are presented, commencing with a singular opportunity to submit Letters of Intent for Public Surveys during the first five years of 4MOST operations.
|
|
| 2. |
- Guerreiro, R., et al.
(författare)
-
Heritability and genetic variance of dementia with Lewy bodies
- 2019
-
Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 127, s. 492-501
-
Tidskriftsartikel (refereegranskat)abstract
- Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants. © 2019 Elsevier Inc.
|
|
| 3. |
- Guerreiro, R., et al.
(författare)
-
Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study
- 2018
-
Ingår i: Lancet Neurology. - 1474-4422. ; 17:1, s. 64-74
-
Tidskriftsartikel (refereegranskat)abstract
- Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI 2.14-2.70; p=1.05 x 10-48), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x 10(-10)), and GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease.
|
|
| 4. |
- Jabbari, E., et al.
(författare)
-
Diagnosis across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome
- 2020
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 77:3, s. 377-387
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. Objective To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. Design, Setting, Participants This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS–Alzheimer disease (CBS-AD), and CBS–non-AD. Data were analyzed from February 1, through May 1, 2019. Main Outcomes and Measures Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures. Results A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n=76) and patients with PD (n=1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS–non-AD group (AUC, 0.80-0.87; P<.05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P<.05). Conclusions and Relevance These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.
|
|
| 5. |
- Orme, T., et al.
(författare)
-
Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies
- 2020
-
Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.
|
|
| 6. |
- Dujon, B, et al.
(författare)
-
The nucleotide sequence of Saccharomyces cerevisiae chromosome XV
- 1997
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 387:6632, s. 98-102
-
Tidskriftsartikel (refereegranskat)abstract
- Chromosome XV was one of the last two chromosomes of Saccharomyces cerevisiae to be discovered(1). It is the third-largest yeast chromosome after chromosomes XII and IV, and is very similar in size to chromosome VII. It alone represents 9% of the yeast genome (8% if ribosomal DNA is included). When systematic sequencing of chromosome XV was started, 93 genes or markers were identified, and most of them were mapped(2). However, very little else was known about chromosome XV which, in contrast to shorter chromosomes, had not been the object of comprehensive genetic or molecular analysis. It was therefore decided to start sequencing chromosome XV only in the third phase of the European Yeast Genome Sequencing Programme, after experience was gained on chromosomes III, XI and II (refs 3-5). The sequence of chromosome XV has been determined from a set of partly overlapping cosmid clones derived from a unique yeast strain, and physically mapped at 3.3-kilobase resolution before sequencing. As well as numerous new open reading frames (ORFs) and genes encoding tRNA or small RNA molecules, the sequence of 1,091,283 base pairs confirms the high proportion of orphan genes and reveals a number of ancestral and successive duplications with other yeast chromosomes.
|
|
| 7. |
- Street, D., et al.
(författare)
-
Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials
- 2023
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 146:8, s. 3232-3242
-
Tidskriftsartikel (refereegranskat)abstract
- Street et al. compare candidate clinical trial end points in progressive supranuclear palsy, multiple system atrophy, corticobasal syndrome and related disorders. Neuroimaging metrics generally enable lower sample sizes than cognitive and functional measures, although optimal outcome measures vary by disease and subtype. The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 +/- 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.
|
|
| 8. |
|
|
| 9. |
- De Jong, R. S., et al.
(författare)
-
4MOST - 4-metre multi-object spectroscopic telescope
- 2012
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819491473 ; , s. 84460T-
-
Konferensbidrag (refereegranskat)abstract
- The 4MOST consortium is currently halfway through a Conceptual Design study for ESO with the aim to develop a wide-field (>3 square degree, goal >5 square degree), high-multiplex (>1500 fibres, goal 3000 fibres) spectroscopic survey facility for an ESO 4m-class telescope (VISTA). 4MOST will run permanently on the telescope to perform a 5 year public survey yielding more than 20 million spectra at resolution R∼5000 (λ=390-1000 nm) and more than 2 million spectra at R∼20,000 (395-456.5 nm & 587-673 nm). The 4MOST design is especially intended to complement three key all-sky, space-based observatories of prime European interest: Gaia, eROSITA and Euclid. Initial design and performance estimates for the wide-field corrector concepts are presented. Two fibre positioner concepts are being considered for 4MOST. The first one is a Phi-Theta system similar to ones used on existing and planned facilities. The second one is a new R-Theta concept with large patrol area. Both positioner concepts effectively address the issues of fibre focus and pupil pointing. The 4MOST spectrographs are fixed configuration two-arm spectrographs, with dedicated spectrographs for the high- and low-resolution fibres. A full facility simulator is being developed to guide trade-off decisions regarding the optimal field-of-view, number of fibres needed, and the relative fraction of high-to-low resolution fibres. The simulator takes mock catalogues with template spectra from Design Reference Surveys as starting point, calculates the output spectra based on a throughput simulator, assigns targets to fibres based on the capabilities of the fibre positioner designs, and calculates the required survey time by tiling the fields on the sky. The 4MOST consortium aims to deliver the full 4MOST facility by the end of 2018 and start delivering high-level data products for both consortium and ESO community targets a year later with yearly increments.
|
|
| 10. |
- Bardella, C., et al.
(författare)
-
Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis
- 2016
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108. ; 30:4, s. 578-594
-
Tidskriftsartikel (refereegranskat)abstract
- Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced alpha-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded,, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gate rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.
|
|
| 11. |
- Kovacs, Gabor G., et al.
(författare)
-
Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
-
Tidskriftsartikel (refereegranskat)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
|
|
| 12. |
- Kun-Rodrigues, Celia, et al.
(författare)
-
A comprehensive screening of copy number variability in dementia with Lewy bodies.
- 2019
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 75
-
Tidskriftsartikel (refereegranskat)abstract
- The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.
|
|
| 13. |
- Kun-Rodrigues, Celia, et al.
(författare)
-
Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies
- 2017
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 49
-
Tidskriftsartikel (refereegranskat)abstract
- . C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of . C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of . C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that . C9orf72 repeat expansions are not causally associated with DLB.
|
|
| 14. |
- Richard, G., et al.
(författare)
-
Multi Modal Verification for Teleservices and Security Applications (M2VTS)
- 1999
-
Ingår i: IEEE International Conference on Multimedia Computing and Systems. - Los Alamitos : IEEE. - 0769502539 ; , s. 1061-1064
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents the European ACTS project M2VTS which stands for Multi Modal Verification for Teleservices and Security Applications. The primary goal of this project is to address the issue of secured access to local and centralised services in a multimedia environment. The main objective is to extend the scope of application of network-based services by adding novel and intelligent functionalities, enabled by automatic verification systems combining multimodal strategies (secured access based on speech, image or other information). The objectives of the project are also to show that limitations of individual technologies (speaker verification, frontal face authentication, profile identification,...) can be overcome by relying on multi-modal decisions (combination or fusion of these technologies).
|
|
| 15. |
|
|
| 16. |
- Bruneton, M., V. Farra, H. A. Pedersen & the SVEKALAPKO Seismic Tomography Working Group, (G. Bock, U. Achauer, A. Alinaghi, J. Ansorge, M. Bruneton, W. Friederich, M. Grad, A. Guterch, S.-E. Hjelt, T. Hyvönen, J.-P. Ikonen, E. Kissling, K. Komminaho, A.
(författare)
-
Non-linear surface wave phase velocity inversion based on ray theory.
- 2002
-
Ingår i: Geophys. J. Int. ; 151, s. 583-596
-
Tidskriftsartikel (refereegranskat)
|
|
| 17. |
- De Jong, Roelof S., et al.
(författare)
-
4MOST : The 4-metre Multi-Object Spectroscopic Telescope project at preliminary design review
- 2016
-
Ingår i: Ground-Based and Airborne Instrumentation for Astronomy VI. - : SPIE. - 0277-786X .- 1996-756X. - 9781510601956 ; 9908
-
Konferensbidrag (refereegranskat)abstract
- We present an overview of the 4MOST project at the Preliminary Design Review. 4MOST is a major new wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of ESO. 4MOST has a broad range of science goals ranging from Galactic Archaeology and stellar physics to the high-energy physics, galaxy evolution, and cosmology. Starting in 2021, 4MOST will deploy 2436 fibres in a 4.1 square degree field-of-view using a positioner based on the tilting spine principle. The fibres will feed one high-resolution (R∼20,000) and two medium resolution (R∼5000) spectrographs with fixed 3-channel designs and identical 6k x 6k CCD detectors. 4MOST will have a unique operations concept in which 5-year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept, showing that we can expect to observe more than 25 million objects in each 5-year survey period and will eventually be used to plan and conduct the actual survey.
|
|
| 18. |
- Guerreiro, Rita, et al.
(författare)
-
Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
- 2016
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 38, s. 7-214
-
Tidskriftsartikel (refereegranskat)abstract
- The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
|
|
| 19. |
- Majounie, Elisa, et al.
(författare)
-
Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study
- 2012
-
Ingår i: Lancet Neurology. - 1474-4465. ; 11:4, s. 323-330
-
Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. Findings In patients with sporadic ALS, we identified the repeat expansion in 236 (7.0%) of 3377 white individuals from the USA, Europe, and Australia, two (4.1%) of 49 black individuals from the USA, and six (8.3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39.3%) of 552 white individuals with familial MS from Europe and the USA. 59 (6.0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24.8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic MS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. Interpretation A common Mendelian genetic lesion in C9472 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.
|
|
| 20. |
- SVEKALAPKO Seismic Tomography Working Group (SSTWG): G. Bock, U. Achauer, A. Alinaghi, J. Ansorge, M. Bruneton, W. Friederich, M. Grad, A. Guterch, S.-E. Hjelt, T. Hyvönen, J.-P. Ikonen, E. Kissling, K. Komminaho, A. Korja, P. Heikkinen, E. Kozlovskaya, M
(författare)
-
Seismic probing of Fennoscandian Lithosphere
- 2002
-
Ingår i: EOS, Trans. Am. geophys. Un.. ; 82:621, s. 628-629
-
Tidskriftsartikel (refereegranskat)
|
|
| 21. |
- Treasure, Anne M., et al.
(författare)
-
Marine Mammals Exploring the Oceans Pole to Pole A Review of the MEOP Consortium
- 2017
-
Ingår i: Oceanography. - : The Oceanography Society. - 1042-8275. ; 30:2, s. 132-138
-
Tidskriftsartikel (refereegranskat)abstract
- Polar oceans are poorly monitored despite the important role they play in regulating Earth's climate system. Marine mammals equipped with biologging devices are now being used to fill the data gaps in these logistically difficult to sample regions. Since 2002, instrumented animals have been generating exceptionally large data sets of oceanographic CTD casts (>500,000 profiles), which are now freely available to the scientific community through the MEOP data portal (http://meop.net). MEOP (Marine Mammals Exploring the Oceans Pole to Pole) is a consortium of international researchers dedicated to sharing animal-derived data and knowledge about the polar oceans. Collectively, MEOP demonstrates the power and cost-effectiveness of using marine mammals as data-collection platforms that can dramatically improve the ocean observing system for biological and physical oceanographers. Here, we review the MEOP program and database to bring it to the attention of the international community.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Ansorge, C, et al.
(författare)
-
Diagnostic value of abdominal drainage in individual risk assessment of pancreatic fistula following pancreaticoduodenectomy
- 2014
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 101:2, s. 100-108
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe use of prophylactic abdominal drainage following pancreaticoduodenectomy (PD) is controversial as its therapeutic value is uncertain. However, the diagnosis of postoperative pancreatic fistula (POPF), the main cause of PD-associated morbidity, is often based on drain pancreatic amylase (DPA) levels. The aim of this study was to assess the predictive value of DPA, plasma pancreatic amylase (PPA) and serum C-reactive protein (CRP) for diagnosing POPF after PD.MethodsPatients undergoing PD with prophylactic drainage between 2008 and 2012 were studied prospectively. DPA, PPA and CRP levels were obtained daily. Differences between groups with clinically relevant POPF (International Study Group on Pancreatic Fistula (ISGPF) grade B/C) and without clinically relevant POPF (no POPF or ISGPF grade A) were evaluated. Receiver operating characteristic (ROC) analyses were performed to determine the value of DPA, PPA and CRP in prediction of POPF. Risk profiles for clinically relevant POPF were constructed and related to the intraoperative pancreatic risk assessment.ResultsFifty-nine (18·7 per cent) of 315 patients developed clinically relevant POPF. DPA, PPA and CRP levels on postoperative day (POD) 1–3 differed significantly between the study groups. In predicting POPF, the DPA level on POD 1 (cut-off at 1322 units/l; odds ratio (OR) 24·61, 95 per cent confidence interval 11·55 to 52·42) and POD 2 (cut-off at 314 units/l; OR 35·45, 14·07 to 89·33) was superior to that of PPA on POD 1 (cut-off at 177 units/l; OR 13·67, 6·46 to 28·94) and POD 2 (cut-off at 98 units/l; OR 16·97, 8·33 to 34·59). When DPA was combined with CRP (cut-off on POD 3 at 202 mg/l; OR 16·98, 8·43 to 34·21), 90·3 per cent of postoperative courses could be predicted correctly (OR 44·14, 16·89 to 115·38).ConclusionThe combination of serum CRP and DPA adequately predicted the development of clinically relevant pancreatic fistula following PD.
|
|
| 25. |
|
|
| 26. |
- Bras, Jose, et al.
(författare)
-
Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
- 2014
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 23:23, s. 6139-6146
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
|
|
| 27. |
- de Jong, Roelof S., et al.
(författare)
-
4MOST-4-metre Multi-Object Spectroscopic Telescope
- 2014
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147
-
Konferensbidrag (refereegranskat)abstract
- 4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with similar to 2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; similar to 1600 fibres go to two spectrographs with resolution R> 5000 (lambda similar to 390-930 nm) and similar to 800 fibres to a spectrograph with R> 18,000 (lambda similar to 392-437 nm & 515-572 nm & 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- du Plessis, M., et al.
(författare)
-
Submesoscale processes promote seasonal restratification in the Subantarctic Ocean
- 2017
-
Ingår i: Journal of Geophysical Research-Oceans. - : American Geophysical Union (AGU). - 2169-9275 .- 2169-9291. ; 122:4, s. 2960-2975
-
Tidskriftsartikel (refereegranskat)abstract
- Traditionally, the mechanism driving the seasonal restratification of the Southern Ocean mixed layer (ML) is thought to be the onset of springtime warming. Recent developments in numerical modeling and North Atlantic observations have shown that submesoscale ML eddies (MLE) can drive a restratifying flux to shoal the deep winter ML prior to solar heating at high latitudes. The impact of submesoscale processes on the intraseasonal variability of the Subantarctic ML is still relatively unknown. We compare 5 months of glider data in the Subantarctic Zone to simulations of a 1-D mixing model to show that the magnitude of restratification of the ML cannot be explained by heat, freshwater, and momentum fluxes alone. During early spring, we estimate that periodic increases in the vertical buoyancy flux by MLEs caused small increases in stratification, despite predominantly down-front winds that promote the destruction of stratification. The timing of seasonal restratification was consistent between 1-D model estimates and the observations. However, during up-front winds, the strength of springtime stratification increased over twofold compared to the 1-D model, with a rapid shoaling of the MLD from >200 m to <100 m within a few days. The ML stratification is further modified under a negative Ekman buoyancy flux during down-front winds, resulting in the destruction of ML stratification and deepening of the MLD. These results propose the importance of submesoscale buoyancy fluxes enhancing seasonal restratification and mixing of the Subantarctic ML.
|
|
| 34. |
- Insulander, J., et al.
(författare)
-
Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma
- 2016
-
Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:9, s. 1200-1208
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival.Methods: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test.Results: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79·3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8·0 versus 14·4 months in locally advanced PDAC, P = 0·007; 2·3 versus 8·0 months in metastatic PDAC, P < 0·001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16·3 versus 10·3 months; P = 0·040).Conclusion: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable.
|
|
| 35. |
- Juhlin, Christopher, et al.
(författare)
-
Crustal structure of the Middle Urals: Results from the (ESRU) Europrobe seismic reflection profiling in the Urals experiments
- 1998
-
Ingår i: Tectonics. - : American Geophysical Union (AGU). - 0278-7407 .- 1944-9194. ; 17:5, s. 710-725
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- As a contribution to Europrobe's seismic reflection profiling in the Urals (ESRU)project, three overlapping seismic reflection data sets were acquired in the Middle Urals. A 56 km long profile was registered over the Europe-Asia suture, two 25 km long intersecting profiles were collected over the Urals superdeep borehole (SG4), and an 80 km long profile was recorded eastward extending east toward the West Siberian Basin. Reflections on the seismic sections delineate several major middle to late Paleozoic thrust zones in the upper crust. These thrust zones have a bivergent geometry with westerly vergence west of the Uralian orogenic axis and easterly vergence to the east. The principal terrane boundaries are the Main Uralian Thrust Fault in the west and the Trans- Uralian Thrust Zone in the east. Normal faults are spatially associated with former thrust faults, or they crosscut them. The thrust and normal faults can be confidently correlated with surface geological features. Near-vertical and wide-angle seismic reflection profiling reveals thickening of the crust from about 45 km to approximately 53 km below the central axis of the Urals. East and west of the root zone, the lower crust is reflective, particularly toward the West Siberian Basin. We interpret the reflectivity of the crust below the East European Craton as pre-Uralian, whereas that toward the West Siberian Basin is interpreted as late orogenic. Although the principal tectonic features imaged by the seismic sections are probably of Paleozoic age, a post-Paleozoic origin for the lower crustal reflectivity in the east cannot be ruled out.
|
|
| 36. |
- Kovacs, Gabor G, et al.
(författare)
-
Neuropathology of the hippocampus in FTLD-Tau with Pick bodies : A study of the BrainNet Europe Consortium
- 2013
-
Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 39:2, s. 166-178
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Frontotemporal lobar degeneration with Pick bodies (Pick's disease) is characterized by the presence of tau immunoreactive spherical structures in the cytoplasm of neurons. In view of confusion about the molecular pathology of Pick's disease, we aimed to evaluate the spectrum of tau pathology and concomitant neurodegeneration-associated protein depositions in the characteristically affected hippocampus. Methods: We evaluated immunoreactivity for tau (AT8, 3R, 4R), α-synuclein, TDP43, p62, and ubiquitin in the hippocampus, entorhinal and temporal cortex in 66 archival cases diagnosed neuropathologically as Pick's disease. Results: Mean age at death was 68.2 years (range 49 to 96). Fifty-two (79%) brains showed 3R immunoreactive spherical inclusions in the granule cells of the dentate gyrus. These typical cases presented mainly with the behavioural variant of FTD, followed by progressive aphasia, mixed syndromes or early memory disturbance. α-Synuclein immunoreactivity was seen only in occasional spherical tau-positive inclusions, TDP-43 IR was absent, and 4R IR was present only as neurofibrillary tangles in pyramidal neurons. Aβ immunoreactivity was observed in 16 cases; however, the overall level of Alzheimer's disease-related alterations was mainly low or intermediate (n = 3). Furthermore, we identified six cases with unclassifiable tauopathy. Conclusions: 1) Pick's disease may occur also in elderly patients and is characterized by a relatively uniform pathology with 3R tau inclusions particularly in the granule cells of dentate gyrus; 2) even minor deviation from these morphological criteria suggests a different disorder; and 3) immunohistological revision of archival cases expands the spectrum of tauopathies that require further classification.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
- Sanjeevi, Srinivas, et al.
(författare)
-
Impact of delay between imaging and treatment in patients with potentially curable pancreatic cancer
- 2015
-
Ingår i: British Journal of Surgery. - : John Wiley & Sons. - 0007-1323 .- 1365-2168. ; 103:3, s. 267-275
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Locoregional pancreatic ductal adenocarcinoma (PDAC) may progress rapidly and/or disseminate despite having an early stage at diagnostic imaging. A prolonged interval from imaging to resection might represent a risk factor for encountering tumour progression at laparotomy. The aim of this study was to determine the therapeutic window for timely surgical intervention.Methods: This observational cohort study included patients with histologically confirmed PDAC scheduled for resection with curative intent from 2008 to 2014. The impact of imaging-to-resection/reassessment (IR) interval, vascular involvement and tumour size on local tumour progression or presence of metastases at reimaging or laparotomy was evaluated using univariable and multivariable regression. Risk estimates were approximated using hazard ratios (HRs).Results: Median IR interval was 42 days. Of 349 patients scheduled for resection, 82 had unresectable disease (resectability rate 76.5 per cent). The unresectability rate was zero when the IR interval was 22 days or shorter, and was lower for an IR interval of 32 days or less compared with longer waiting times (13 versus 26.2 per cent; HR 0.42, P = 0.021). It was also lower for tumours smaller than 30 mm than for larger tumours (13.9 versus 32.5 per cent; HR 0.34, P < 0.001). Tumours with no or minor vascular involvement showed decreased rates of unresectable disease (20.6 per cent versus 38 per cent when there was major or combined vascular involvement; HR 0.43, P = 0.007). However, this failed to reach statistical significance on multivariable analysis (P = 0.411), in contrast to IR interval (P = 0.028) and tumour size (P < 0.001).Conclusion: Operation within 32 days of diagnostic imaging reduced the risk of tumour progression to unresectable disease by half compared with a longer waiting time. The results of this study highlight the importance of efficient clinical PDAC management.
|
|
| 41. |
- Wennerblom, Johanna, 1969, et al.
(författare)
-
Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy: multicentre randomized clinical trial
- 2021
-
Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:3, s. 265-270
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postoperative pancreatic fistula is the leading cause of morbidity after distal pancreatectomy. Strategies investigated to reduce the incidence have been disappointing. Recent data showed a reduction in postoperative pancreatic fistula with the use of synthetic mesh reinforcement of the staple line. METHODS: An RCT was conducted between May 2014 and February 2016 at four tertiary referral centres in Sweden. Patients scheduled for distal pancreatectomy were eligible. Enrolled patients were randomized during surgery to stapler transection with biological reinforcement or standard stapler transection. Patients were blinded to the allocation. The primary endpoint was the development of any postoperative pancreatic fistula. Secondary endpoints included morbidity, mortality, and duration of hospital stay. RESULTS: Some 107 patients were randomized and 106 included in an intention-to-treat analysis (56 in reinforced stapling group, 50 in standard stapling group). No difference was demonstrated in terms of clinically relevant fistulas (grade B and C): 6 of 56 (11 per cent) with reinforced stapling versus 8 of 50 (16 per cent) with standard stapling (P=0.332). There was no difference between groups in overall postoperative complications: 45 (80 per cent) and 39 (78 per cent) in reinforced and standard stapling groups respectively (P=0.765). Duration of hospital stay was comparable: median 8 (range 2-35) and 9 (2-114) days respectively (P=0.541). CONCLUSION: Biodegradable stapler reinforcement at the transection line of the pancreas did not reduce postoperative pancreatic fistula compared with regular stapler transection in distal pancreatectomy. Registration number: NCT02149446 (http://www.clinicaltrials.gov). © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.
|
|
