| 1. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 2. |
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| 3. |
- Jonsson, Lina, 1982, et al.
(författare)
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Characterisation of age and polarity at onset in bipolar disorder
- 2021
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669
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Tidskriftsartikel (refereegranskat)abstract
- Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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| 4. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 5. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 6. |
- Rosser, Z H, et al.
(författare)
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Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.
- 2000
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 67:6, s. 1526-43
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Tidskriftsartikel (refereegranskat)abstract
- Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.
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| 7. |
- Charney, A. W., et al.
(författare)
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Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder
- 2017
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P = 3.28 x 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2) = 0.35; BD II SNP-h(2) = 0.25; P = 0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
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| 8. |
- van Rheenen, Wouter, et al.
(författare)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 9. |
- Bale, S. D., et al.
(författare)
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The FIELDS Instrument Suite for Solar Probe Plus
- 2016
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 204:1-4, s. 49-82
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Forskningsöversikt (refereegranskat)abstract
- NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
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| 10. |
- Charney, Alexander W, et al.
(författare)
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Contribution of Rare Copy Number Variants toBipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p= .001), BD I (p= .0003), and BD II (p= .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p= .0007, PRS p= .004), and BD I without psychosis (CNV p= .0004, PRS p= 3.9× 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p= .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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| 11. |
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| 12. |
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| 13. |
- Ergun, R. E., et al.
(författare)
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Drift waves, intense parallel electric fields, and turbulence associated with asymmetric magnetic reconnection at the magnetopause
- 2017
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 44:7, s. 2978-2986
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Tidskriftsartikel (refereegranskat)abstract
- Observations of magnetic reconnection at Earth's magnetopause often display asymmetric structures that are accompanied by strong magnetic field (B) fluctuations and large-amplitude parallel electric fields (E-||). The B turbulence is most intense at frequencies above the ion cyclotron frequency and below the lower hybrid frequency. The B fluctuations are consistent with a thin, oscillating current sheet that is corrugated along the electron flow direction (along the X line), which is a type of electromagnetic drift wave. Near the X line, electron flow is primarily due to a Hall electric field, which diverts ion flow in asymmetric reconnection and accompanies the instability. Importantly, the drift waves appear to drive strong parallel currents which, in turn, generate large-amplitude (similar to 100mV/m) E-|| in the form of nonlinear waves and structures. These observations suggest that turbulence may be common in asymmetric reconnection, penetrate into the electron diffusion region, and possibly influence the magnetic reconnection process.
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| 14. |
- Gray, E., et al.
(författare)
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A multi-center study of neurofilament assay reliability and inter-laboratory variability
- 2020
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 21:5-6, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Significantly elevated levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) have been described in the blood and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the analytical performance of different neurofilament assays in a round robin with 10 centers across Europe/U.S.Methods: Serum, plasma and CSF samples from a group of five ALS and five neurological control patients were distributed across 10 international specialist neurochemical laboratories for analysis by a range of commercial and in-house neurofilament assays. The performance of all assays was evaluated for their ability to differentiate between the groups. The inter-assay coefficient of variation was calculated where appropriate from sample measurements performed across multiple laboratories using the same assay.Results:All assays could differentiate ALS patients from controls in CSF. Inter-assay coefficient of variation of analytical platforms performed across multiple laboratories varied between 6.5% and 41.9%.Conclusions:This study is encouraging for the growing momentum toward integration of neurofilament measurement into the specialized ALS clinic. It demonstrates the importance of 'round robin' studies necessary to ensure the analytical quality required for translation to the routine clinical setting. A standardized neurofilament probe is needed which can be used as international benchmark for analytical performance in ALS.
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| 15. |
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| 16. |
- Ergun, R. E., et al.
(författare)
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Magnetospheric Multiscale observations of large-amplitude, parallel, electrostatic waves associated with magnetic reconnection at the magnetopause
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:11, s. 5626-5634
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale satellites of large-amplitude, parallel, electrostatic waves associated with magnetic reconnection at the Earth's magnetopause. The observed waves have parallel electric fields (E-||) with amplitudes on the order of 100mV/m and display nonlinear characteristics that suggest a possible net E-||. These waves are observed within the ion diffusion region and adjacent to (within several electron skin depths) the electron diffusion region. They are in or near the magnetosphere side current layer. Simulation results support that the strong electrostatic linear and nonlinear wave activities appear to be driven by a two stream instability, which is a consequence of mixing cold (<10eV) plasma in the magnetosphere with warm (similar to 100eV) plasma from the magnetosheath on a freshly reconnected magnetic field line. The frequent observation of these waves suggests that cold plasma is often present near the magnetopause.
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| 17. |
- Ergun, R. E., et al.
(författare)
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Magnetospheric Multiscale Satellites Observations of Parallel Electric Fields Associated with Magnetic Reconnection
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:23
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale satellites of parallel electric fields (E-vertical bar vertical bar) associated with magnetic reconnection in the subsolar region of the Earth's magnetopause. E-vertical bar vertical bar events near the electron diffusion region have amplitudes on the order of 100 mV/m, which are significantly larger than those predicted for an antiparallel reconnection electric field. This Letter addresses specific types of E-vertical bar vertical bar events, which appear as large-amplitude, near unipolar spikes that are associated with tangled, reconnected magnetic fields. These E-vertical bar vertical bar events are primarily in or near a current layer near the separatrix and are interpreted to be double layers that may be responsible for secondary reconnection in tangled magnetic fields or flux ropes. These results are telling of the three-dimensional nature of magnetopause reconnection and indicate that magnetopause reconnection may be often patchy and/or drive turbulence along the separatrix that results in flux ropes and/or tangled magnetic fields.
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| 18. |
- Eriksson, S., et al.
(författare)
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Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:1
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E-parallel to)that is larger than predicted by simulations. The high-speed (similar to 300 km/s) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E-parallel to is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.
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| 19. |
- Kapoor, M., et al.
(författare)
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Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy
- 2022
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:11, s. 3347-3357
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and examine the usefulness of pNfL concentrations in determining disease remission. Methods We examined pNfL concentrations in treatment-naive CIDP patients (n = 10) before and after intravenous immunoglobulin (IVIg) induction treatment, in pNfL concentrations in patients on maintenance IVIg treatment who had stable (n = 15) versus unstable disease (n = 9), and in clinically stable IVIg-treated patients (n = 10) in whom we suspended IVIg to determine disease activity and ongoing need for maintenance IVIg. pNfL concentrations in an age-matched healthy control group were measured for comparison. Results Among treatment-naive patients, pNfL concentration was higher in patients before IVIg treatment than healthy controls and subsequently reduced to be comparable to control group values after IVIg induction. Among CIDP patients on IVIg treatment, pNfL concentration was significantly higher in unstable patients than stable patients. A pNFL concentration > 16.6 pg/ml distinguished unstable treated CIDP from stable treated CIDP (sensitivity = 86.7%, specificity = 66.7%, area under receiver operating characteristic curve = 0.73). Among the treatment withdrawal group, there was a statistically significant correlation between pNfL concentration at time of IVIg withdrawal and the likelihood of relapse (r = 0.72, p < 0.05), suggesting an association of higher pNfL concentration with active disease. Conclusions pNfL concentrations may be a sensitive, clinically useful biomarker in assessing subclinical disease activity.
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| 20. |
- Stawarz, J. E., et al.
(författare)
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Observations of turbulence in a Kelvin-Helmholtz event on 8 September 2015 by the Magnetospheric Multiscale mission
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing. - 2169-9380 .- 2169-9402. ; 121:11, s. 11021-11034
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Tidskriftsartikel (refereegranskat)abstract
- Spatial and high-time-resolution properties of the velocities, magnetic field, and 3-D electric field within plasma turbulence are examined observationally using data from the Magnetospheric Multiscale mission. Observations from a Kelvin-Helmholtz instability (KHI) on the Earth's magnetopause are examined, which both provides a series of repeatable intervals to analyze, giving better statistics, and provides a first look at the properties of turbulence in the KHI. For the first time direct observations of both the high-frequency ion and electron velocity spectra are examined, showing differing ion and electron behavior at kinetic scales. Temporal spectra exhibit power law behavior with changes in slope near the ion gyrofrequency and lower hybrid frequency. The work provides the first observational evidence for turbulent intermittency and anisotropy consistent with quasi two-dimensional turbulence in association with the KHI. The behavior of kinetic-scale intermittency is found to have differences from previous studies of solar wind turbulence, leading to novel insights on the turbulent dynamics in the KHI.
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| 21. |
- Kapoor, M., et al.
(författare)
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Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis
- 2019
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 24:4, s. 314-319
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of a multisystem disorder. The recent development of highly effective gene silencing therapies has highlighted the need for effective biomarkers of disease activity to guide the decision of when to start and stop treatment. In this study, we measured plasma neurofilament light chain (pNfL) concentration in 73 patients with ATTR and found that pNfL was significantly raised in ATTRm patients with peripheral neuropathy compared to healthy controls. Furthermore, pNFL correlated with disease severity as defined by established clinical outcome measures in patients for whom this information was available. These findings suggest a potential role of pNfL in monitoring disease activity and progression in ATTRm patients.
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| 22. |
- Wilder, F. D., et al.
(författare)
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Observations of large-amplitude, parallel, electrostatic waves associated with the Kelvin-Helmholtz instability by the magnetospheric multiscale mission
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:17, s. 8859-8866
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Tidskriftsartikel (refereegranskat)abstract
- On 8 September 2015, the four Magnetospheric Multiscale spacecraft encountered a Kelvin-Helmholtz unstable magnetopause near the dusk flank. The spacecraft observed periodic compressed current sheets, between which the plasma was turbulent. We present observations of large-amplitude (up to 100 mV/m) oscillations in the electric field. Because these oscillations are purely parallel to the background magnetic field, electrostatic, and below the ion plasma frequency, they are likely to be ion acoustic-like waves. These waves are observed in a turbulent plasma where multiple particle populations are intermittently mixed, including cold electrons with energies less than 10 eV. Stability analysis suggests a cold electron component is necessary for wave growth.
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| 23. |
- Wilder, F. D., et al.
(författare)
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Observations of whistler mode waves with nonlinear parallel electric fields near the dayside magnetic reconnection separatrix by the Magnetospheric Multiscale mission
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:12, s. 5909-5917
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Tidskriftsartikel (refereegranskat)abstract
- We show observations from the Magnetospheric Multiscale (MMS) mission of whistler mode waves in the Earth's low-latitude boundary layer (LLBL) during a magnetic reconnection event. The waves propagated obliquely to the magnetic field toward the X line and were confined to the edge of a southward jet in the LLBL. Bipolar parallel electric fields interpreted as electrostatic solitary waves (ESW) are observed intermittently and appear to be in phase with the parallel component of the whistler oscillations. The polarity of the ESWs suggests that if they propagate with the waves, they are electron enhancements as opposed to electron holes. The reduced electron distribution shows a shoulder in the distribution for parallel velocities between 17,000 and 22,000 km/s, which persisted during the interval when ESWs were observed, and is near the phase velocity of the whistlers. This shoulder can drive Langmuir waves, which were observed in the high-frequency parallel electric field data.
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| 24. |
- Camu, W., et al.
(författare)
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Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial
- 2020
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-dose interleukin-2 (ld-IL-2) enhances regulatory T-cell (Treg) function in auto-inflammatory conditions. Neuroinflammation being a pathogenic feature of amyotrophic lateral sclerosis (ALS), we evaluated the pharmacodynamics and safety of ld-IL-2 in ALS subjects. Methods: We performed a single centre, parallel three-arm, randomised, double-blind, placebo-controlled study. Eligibility criteria included age < 75 years, disease duration < 5 years, riluzole treatment > 3 months, and a slow vital capacity ≥ 70% of normal. Patients were randomised (1:1:1) to aldesleukin 2 MIU, 1 MIU, or placebo once daily for 5 days every 4 weeks for 3 cycles. Primary outcome was change from baseline in Treg percentage of CD4+ T cells (%Tregs) following a first cycle. Secondary laboratory outcomes included: %Treg and Treg number following repeated cycles, and plasma CCL2 and neurofilament light chain protein (NFL) concentrations as surrogate markers of efficacy. Safety outcomes included motor-function (ALSFRS-R), slow vital capacity (SVC), and adverse event reports. This trial is registered with ClinicalTrials.gov, NCT02059759. Findings: All randomised patients (12 per group), recruited from October 2015 to December 2015, were alive at the end of follow-up and included in the intent-to-treat (ITT) analysis. No drug-related serious adverse event was observed. Non-serious adverse events occurred more frequently with the 1 and 2 MIU IL-2 doses compared to placebo, including injection site reactions and flu-like symptoms. Primary outcome analysis showed a significant increase (p < 0·0001) in %Tregs in the 2 MIU and 1 MIU arms (mean [SD]: 2 MIU: +6·2% [2·2]; 1 MIU: +3·9% [1·2]) as compared to placebo (mean [SD]: -0·49% [1·3]). Effect sizes (ES) were large in treated groups: 2 MIU ES=3·7 (IC95%: 2·3–4·9) and 1 MIU ES=3·5 (IC95%: 2·1–4·6). Secondary outcomes showed a significant increase in %Tregs following repeated cycles (p < 0·0001) as compared to placebo, and a dose-dependent decrease in plasma CCL2 (p = 0·0049). There were no significant differences amongst the three groups on plasma NFL levels. Interpretation: Ld-IL-2 is well tolerated and immunologically effective in subjects with ALS. These results warrant further investigation into their eventual therapeutic impact on slowing ALS disease progression. Funding: : The French Health Ministry (PHRC-I-14-056), EU H2020 (grant #633413), and the Association pour la Recherche sur la SLA (ARSLA). © 2020 The Authors
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| 25. |
- Chen, L. -J, et al.
(författare)
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Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:22
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Tidskriftsartikel (refereegranskat)abstract
- Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.
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| 26. |
- Gallo, V., et al.
(författare)
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BRain health and healthy AgeINg in retired rugby union players, the BRAIN Study: study protocol for an observational study in the UK
- 2017
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Relatively little is known about the long-term health of former elite rugby players, or former sportspeople more generally. As well as the potential benefits of being former elite sportspersons, there may be potential health risks from exposures occurring during an individual's playing career, as well as following retirement. Each contact sport has vastly different playing dynamics, therefore exposing its players to different types of potential traumas. Current evidence suggests that these are not necessarily comparable in terms of pathophysiology, and their potential long-term adverse effects might also differ. There is currently limited but increasing evidence that poorer age-related and neurological health exists among former professional sportsmen exposed to repetitive concussions; however the evidence is limited on rugby union players, specifically. Methods and analysis We present the protocol for a cross-sectional study to assess the association between self-reported history of concussion during a playing career, and subsequent measures of healthy ageing and neurological and cognitive impairment. We are recruiting a sample of approximately 200 retired rugby players (former Oxford and Cambridge University rugby players and members of the England Rugby International Club) aged 50 years or more, and collecting a number of general and neurological health-related outcome measures though validated assessments. Biomarkers of neurodegeneration (neurofilaments and tau) will be also be measured. Although the study is focusing on rugby union players specifically, the general study design and the methods for assessing neurological health are likely to be relevant to other studies of former elite sportspersons. Ethics and dissemination The study has been approved by the Ethical Committee of London School of Hygiene and Tropical Medicine (reference: 11634-2). It is intended that results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders.
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| 27. |
- Lombardi, V., et al.
(författare)
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Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity. In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity. While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.
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| 28. |
- Wilder, F. D., et al.
(författare)
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The nonlinear behavior of whistler waves at the reconnecting dayside magnetopause as observed by the Magnetospheric Multiscale mission : A case study
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing Ltd. - 2169-9380 .- 2169-9402. ; 122:5, s. 5487-5501
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Tidskriftsartikel (refereegranskat)abstract
- We show observations of whistler mode waves in both the low-latitude boundary layer (LLBL) and on closed magnetospheric field lines during a crossing of the dayside reconnecting magnetopause by the Magnetospheric Multiscale (MMS) mission on 11 October 2015. The whistlers in the LLBL were on the electron edge of the magnetospheric separatrix and exhibited high propagation angles with respect to the background field, approaching 40°, with bursty and nonlinear parallel electric field signatures. The whistlers in the closed magnetosphere had Poynting flux that was more field aligned. Comparing the reduced electron distributions for each event, the magnetospheric whistlers appear to be consistent with anisotropy-driven waves, while the distribution in the LLBL case includes anisotropic backward resonant electrons and a forward resonant beam at near half the electron-Alfvén speed. Results are compared with the previously published observations by MMS on 19 September 2015 of LLBL whistler waves. The observations suggest that whistlers in the LLBL can be both beam and anisotropy driven, and the relative contribution of each might depend on the distance from the X line.
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| 29. |
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| 30. |
- Andersson, L., et al.
(författare)
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Dust observations at orbital altitudes surrounding Mars
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
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Tidskriftsartikel (refereegranskat)abstract
- Dust is common close to the martian surface, but no known process can lift appreciable concentrations of particles to altitudes above similar to 150 kilometers. We present observations of dust at altitudes ranging from 150 to above 1000 kilometers by the Langmuir Probe and Wave instrument on the Mars Atmosphere and Volatile Evolution spacecraft. Based on its distribution, we interpret this dust to be interplanetary in origin. A comparison with laboratory measurements indicates that the dust grain size ranges from 1 to 12 micrometers, assuming a typical grain velocity of similar to 18 kilometers per second. These direct observations of dust entering the martian atmosphere improve our understanding of the sources, sinks, and transport of interplanetary dust throughout the inner solar system and the associated impacts on Mars's atmosphere.
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| 31. |
- Bigdeli, TB, et al.
(författare)
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Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry
- 2020
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 25:10, s. 2455-2467
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.
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| 32. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 33. |
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| 34. |
- Ergun, R. E., et al.
(författare)
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The Axial Double Probe and Fields Signal Processing for the MMS Mission
- 2016
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Ingår i: Space Science Reviews. - : Springer Netherlands. - 0038-6308 .- 1572-9672. ; 199:1-4, s. 167-188
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Forskningsöversikt (refereegranskat)abstract
- The Axial Double Probe (ADP) instrument measures the DC to similar to 100 kHz electric field along the spin axis of the Magnetospheric Multiscale (MMS) spacecraft (Burch et al., Space Sci. Rev., 2014, this issue), completing the vector electric field when combined with the spin plane double probes (SDP) (Torbert et al., Space Sci. Rev., 2014, this issue, Lindqvist et al., Space Sci. Rev., 2014, this issue). Two cylindrical sensors are separated by over 30 m tip-to-tip, the longest baseline on an axial DC electric field ever attempted in space. The ADP on each of the spacecraft consists of two identical, 12.67 m graphite coilable booms with second, smaller 2.25 m booms mounted on their ends. A significant effort was carried out to assure that the potential field of the MMS spacecraft acts equally on the two sensors and that photo- and secondary electron currents do not vary over the spacecraft spin. The ADP on MMS is expected to measure DC electric field with a precision of similar to 1 mV/m, a resolution of similar to 25 mu V/m, and a range of similar to 1 V/m in most of the plasma environments MMS will encounter. The Digital Signal Processing (DSP) units on the MMS spacecraft are designed to perform analog conditioning, analog-to-digital (A/D) conversion, and digital processing on the ADP, SDP, and search coil magnetometer (SCM) (Le Contel et al., Space Sci. Rev., 2014, this issue) signals. The DSP units include digital filters, spectral processing, a high-speed burst memory, a solitary structure detector, and data compression. The DSP uses precision analog processing with, in most cases, > 100 dB in dynamic range, better that -80 dB common mode rejection in electric field (E) signal processing, and better that -80 dB cross talk between the E and SCM (B) signals. The A/D conversion is at 16 bits with similar to 1/4 LSB accuracy and similar to 1 LSB noise. The digital signal processing is powerful and highly flexible allowing for maximum scientific return under a limited telemetry volume. The ADP and DSP are described in this article.
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| 35. |
- Gallo, V., et al.
(författare)
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Concussion and long-term cognitive function among rugby players-The BRAIN Study
- 2022
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:6, s. 1164-1176
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The BRAIN Study was established to assess the associations between self-reported concussions and cognitive function among retired rugby players. Methods Former elite-level male rugby union players (50+ years) in England were recruited. Exposure to rugby-related concussion was collected using the BRAIN-Q tool. The primary outcome measure was the Preclinical Alzheimer Cognitive Composite (PACC). Linear regressions were conducted for the association between concussion and PACC score, adjusting for confounders. Results A total of 146 participants were recruited. The mean (standard deviation) length of playing career was 15.8 (5.4) years. A total of 79.5% reported rugby-related concussion(s). No association was found between concussion and PACC (beta -0.03 [95% confidence interval (CI): -1.31, 0.26]). However, participants aged 80+ years reporting 3+ concussions had worse cognitive function than those without concussion (beta -1.04 [95% CI: -1.62, -0.47]). Conclusions Overall there was no association between concussion and cognitive function; however, a significant interaction with age revealed an association in older participants.
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| 36. |
- Goodrich, Katherine A., et al.
(författare)
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MMS Multipoint electric field observations of small-scale magnetic holes
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:12, s. 5953-5959
-
Tidskriftsartikel (refereegranskat)abstract
- Small-scale magnetic holes (MHs), local depletions in magnetic field strength, have been observed multiple times in the Earth's magnetosphere in the bursty bulk flow (BBF) braking region. This particular subset of MHs has observed scale sizes perpendicular to the background magnetic field (B) less than the ambient ion Larmor radius (rho(i)). Previous observations by Time History of Events and Macroscale Interactions during Substorms (THEMIS) indicate that this subset of MHs can be supported by a current driven by the E x B drift of electrons. Ions do not participate in the E x B drift due to the small-scale size of the electric field. While in the BBF braking region, during its commissioning phase, the Magnetospheric Multiscale (MMS) spacecraft observed a small-scale MH. The electric field observations taken during this event suggest the presence of electron currents perpendicular to the magnetic field. These observations also suggest that these currents can evolve to smaller spatial scales.
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| 37. |
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| 38. |
- Han, D. -S, et al.
(författare)
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Coordinated observations of two types of diffuse auroras near magnetic local noon by Magnetospheric Multiscale mission and ground all-sky camera
- 2017
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 44:16, s. 8130-8139
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Tidskriftsartikel (refereegranskat)abstract
- Structured diffuse auroras are often observed near magnetic local noon (MLN), but their generation mechanisms are poorly understood. We have found that two types of structured diffuse auroras with obviously different dynamical properties often coexist near MLN. One type usually drifts from low to high latitude with higher speed and shows pulsation. The other type is always adjacent to the discrete aurora oval and drifts together with nearby discrete aurora with much lower speed. Using coordinated observations from MMS and ground all-sky imagers, we found that the two types of diffuse auroras are well correlated with number density increase of O+ (from the ionosphere) and of He2+ (from magnetosheath) ions, respectively. These observations indicate that mangetosheath particles penetrated into the magnetosphere also can play an important role for producing the dayside diffuse aurora. In addition, for the first time, electron cyclotron harmonic waves are observed associated with dayside diffuse aurora.
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| 39. |
- Hansel, P. J., et al.
(författare)
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Mapping MMS Observations of Solitary Waves in Earth's Magnetic Field
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:12
-
Tidskriftsartikel (refereegranskat)abstract
- Electrostatic solitary waves (ESWs) are a type of nonlinear time-domain plasma structure (TDS) generally defined by bipolar electric fields and propagation parallel to the local magnetic field. Formation mechanisms for TDSs in the magnetosphere have been studied extensively and are associated with plasma boundary layers and the braking of bursty bulk flows (BBFs). However, the rapid timescales over which these TDSs occur (<2 ms) make them infeasible to count by eye over large time periods. Furthermore, high-cadence data are not always available. The Solitary Wave Detector (SWD) on NASA's Magnetospheric Multiscale (MMS) mission quantifies the occurrence and amplitude of TDS throughout the constellation's orbit; analysis of burst (65 kS/s) parallel electric field data indicates that the SWD captures approximately 60% of all bipolar TDS encountered in the tail region, enabling large-scale examination of their occurrence. Maps of TDS occurrence rates during several years of the MMS mission were generated from SWD data, showing enhanced TDS density in the tail region between 6 and 9 Re; enhance occurrence in or near shocks; and an unexpected enhancement in the dawn side of the tail and in the radiation belt.
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| 40. |
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| 41. |
- Lewis, Cathryn M, et al.
(författare)
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Genome scan meta-analysis of schizophrenia and bipolar disorder, part II : Schizophrenia
- 2003
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 73:1, s. 34-48
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
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| 42. |
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| 43. |
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| 44. |
- Palmroth, Minna, et al.
(författare)
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Lower-thermosphere-ionosphere (LTI) quantities : current status of measuring techniques and models
- 2021
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Ingår i: Annales Geophysicae. - : Copernicus Publications. - 0992-7689 .- 1432-0576. ; 39:1, s. 189-237
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Tidskriftsartikel (refereegranskat)abstract
- The lower-thermosphere-ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI.
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| 45. |
- Sarris, Theodore E., et al.
(författare)
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Daedalus MASE (mission assessment through simulation exercise): A toolset for analysis of in situ missions and for processing global circulation model outputs in the lower thermosphere-ionosphere
- 2023
-
Ingår i: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Daedalus MASE (Mission Assessment through Simulation Exercise) is an open-source package of scientific analysis tools aimed at research in the Lower Thermosphere-Ionosphere (LTI). It was created with the purpose to assess the performance and demonstrate closure of the mission objectives of Daedalus, a mission concept targeting to perform in-situ measurements in the LTI. However, through its successful usage as a mission-simulator toolset, Daedalus MASE has evolved to encompass numerous capabilities related to LTI science and modeling. Inputs are geophysical observables in the LTI, which can be obtained either through in-situ measurements from spacecraft and rockets, or through Global Circulation Models (GCM). These include ion, neutral and electron densities, ion and neutral composition, ion, electron and neutral temperatures, ion drifts, neutral winds, electric field, and magnetic field. In the examples presented, these geophysical observables are obtained through NCAR’s Thermosphere-Ionosphere-Electrodynamics General Circulation Model. Capabilities of Daedalus MASE include: 1) Calculations of products that are derived from the above geophysical observables, such as Joule heating, energy transfer rates between species, electrical currents, electrical conductivity, ion-neutral collision frequencies between all combinations of species, as well as height-integrations of derived products. 2) Calculation and cross-comparison of collision frequencies and estimates of the effect of using different models of collision frequencies into derived products. 3) Calculation of the uncertainties of derived products based on the uncertainties of the geophysical observables, due to instrument errors or to uncertainties in measurement techniques. 4) Routines for the along-orbit interpolation within gridded datasets of GCMs. 5) Routines for the calculation of the global coverage of an in situ mission in regions of interest and for various conditions of solar and geomagnetic activity. 6) Calculations of the statistical significance of obtaining the primary and derived products throughout an in situ mission’s lifetime. 7) Routines for the visualization of 3D datasets of GCMs and of measurements along orbit. Daedalus MASE code is accompanied by a set of Jupyter Notebooks, incorporating all required theory, references, codes and plotting in a user-friendly environment. Daedalus MASE is developed and maintained at the Department for Electrical and Computer Engineering of the Democritus University of Thrace, with key contributions from several partner institutions.
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| 46. |
- Sproviero, William, et al.
(författare)
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ATXN2 trinucleotide repeat length correlates with risk of ALS
- 2017
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 51, s. 178.e1-178.e9
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Tidskriftsartikel (refereegranskat)abstract
- We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.
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| 47. |
- Telloni, Daniele, et al.
(författare)
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Exploring the Solar Wind from Its Source on the Corona into the Inner Heliosphere during the First Solar Orbiter-Parker Solar Probe Quadrature
- 2021
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics Publishing (IOPP). - 2041-8205 .- 2041-8213. ; 920:1
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Tidskriftsartikel (refereegranskat)abstract
- This Letter addresses the first Solar Orbiter (SO)-Parker Solar Probe (PSP) quadrature, occurring on 2021 January 18 to investigate the evolution of solar wind from the extended corona to the inner heliosphere. Assuming ballistic propagation, the same plasma volume observed remotely in the corona at altitudes between 3.5 and 6.3 solar radii above the solar limb with the Metis coronagraph on SO can be tracked to PSP, orbiting at 0.1 au, thus allowing the local properties of the solar wind to be linked to the coronal source region from where it originated. Thanks to the close approach of PSP to the Sun and the simultaneous Metis observation of the solar corona, the flow-aligned magnetic field and the bulk kinetic energy flux density can be empirically inferred along the coronal current sheet with an unprecedented accuracy, allowing in particular estimation of the Alfven radius at 8.7 solar radii during the time of this event. This is thus the very first study of the same solar wind plasma as it expands from the sub-Alfvenic solar corona to just above the Alfven surface.
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| 48. |
- Telloni, Daniele, et al.
(författare)
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Linking Small-scale Solar Wind Properties with Large-scale Coronal Source Regions through Joint Parker Solar Probe-Metis/Solar Orbiter Observations
- 2022
-
Ingår i: Astrophysical Journal. - : IOP Publishing Ltd. - 0004-637X .- 1538-4357. ; 935:2
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Tidskriftsartikel (refereegranskat)abstract
- The solar wind measured in situ by Parker Solar Probe in the very inner heliosphere is studied in combination with the remote-sensing observation of the coronal source region provided by the METIS coronagraph aboard Solar Orbiter. The coronal outflows observed near the ecliptic by Metis on 2021 January 17 at 16:30 UT, between 3.5 and 6.3 R (circle dot) above the eastern solar limb, can be associated with the streams sampled by PSP at 0.11 and 0.26 au from the Sun, in two time intervals almost 5 days apart. The two plasma flows come from two distinct source regions, characterized by different magnetic field polarity and intensity at the coronal base. It follows that both the global and local properties of the two streams are different. Specifically, the solar wind emanating from the stronger magnetic field region has a lower bulk flux density, as expected, and is in a state of well-developed Alfvenic turbulence, with low intermittency. This is interpreted in terms of slab turbulence in the context of nearly incompressible magnetohydrodynamics. Conversely, the highly intermittent and poorly developed turbulent behavior of the solar wind from the weaker magnetic field region is presumably due to large magnetic deflections most likely attributed to the presence of switchbacks of interchange reconnection origin.
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| 49. |
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