Abstract
We compute the spherically averaged power spectrum from four seasons of data obtained for the Epoch of Reionization (EoR) project observed with the Murchison Widefield Array (MWA). We ...measure the EoR power spectrum over k = 0.07–3.0 h Mpc−1 at redshifts $z$ = 6.5–8.7. The largest aggregation of 110 h on EoR0 high band (3340 observations), yields a lowest measurement of (43 mK)2 = 1.8 × 103 mK2 at k = 0.14 h Mpc−1 and $z$ = 6.5 (2σ thermal noise plus sample variance). Using the Real-Time System to calibrate and the CHIPS pipeline to estimate power spectra, we select the best observations from the central five pointings within the 2013–2016 observing seasons, observing three independent fields and in two frequency bands. This yields 13 591 2-min snapshots (453 h), based on a quality assurance metric that measures ionospheric activity. We perform another cut to remove poorly calibrated data, based on power in the foreground-dominated and EoR-dominated regions of the two-dimensional power spectrum, reducing the set to 12 569 observations (419 h). These data are processed in groups of 20 observations, to retain the capacity to identify poor data, and used to analyse the evolution and structure of the data over field, frequency, and data quality. We subsequently choose the cleanest 8935 observations (298 h of data) to form integrated power spectra over the different fields, pointings, and redshift ranges.
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
There is growing concern about possible cognitive consequences of COVID-19, with reports of ‘Long COVID’ symptoms persisting into the chronic phase and case studies revealing neurological problems in ...severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.
We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.
People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.
Interpretation. These results accord with reports of ‘Long Covid’ cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.
Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The characterization of the Advanced LIGO detectors in the second and third observing runs has increased the sensitivity of the instruments, allowing for a higher number of detectable ...gravitational-wave signals, and provided confirmation of all observed gravitational-wave events. In this work, we present the methods used to characterize the LIGO detectors and curate the publicly available datasets, including the LIGO strain data and data quality products. We describe the essential role of these datasets in LIGO–Virgo Collaboration analyses of gravitational-waves from both transient and persistent sources and include details on the provenance of these datasets in order to support analyses of LIGO data by the broader community. Finally, we explain anticipated changes in the role of detector characterization and current efforts to prepare for the high rate of gravitational-wave alerts and events in future observing runs.
The compact configuration of Phase II of the Murchison Widefield Array (MWA) consists of both a redundant subarray and pseudo-random baselines, offering unique opportunities to perform sky-model and ...redundant interferometric calibration. The highly redundant hexagonal cores give improved power spectrum sensitivity. In this paper, we present the analysis of nearly 40 hr of data targeting one of the MWA's epoch of reionization (EoR) fields observed in 2016. We use both improved analysis techniques presented in Barry et al. and several additional techniques developed for this work, including data quality control methods and interferometric calibration approaches. We show the EoR power spectrum limits at redshift 6.5, 6.8, and 7.1 based on our deep analysis on this 40 hr data set. These limits span a range in k-space of 0.18 h Mpc−1 < k < 1.6 h Mpc−1, with a lowest measurement of Δ2 ≤ 2.39 × 103 mK2 at k = 0.59 h Mpc−1 and z = 6.5.
Prognostic systems for myelodysplasia rely on clinical factors, but particular genetic lesions can influence relapse rate, overall survival, and nonrelapse-related mortality as well as the choice of ...conditioning regimen for hematopoietic stem-cell transplantation.
The myelodysplastic syndrome (MDS) is clinically and biologically heterogeneous. In children and young adults, MDS can arise in the context of congenital mutations that cause bone marrow failure syndromes or inherited predisposition to myeloid cancers.
1
Therapy-related MDS develops as a late complication in patients with previous exposure to chemotherapy, radiation therapy, or both.
2
In most patients, however, primary MDS arises in the absence of an identified exposure, prodromal bone marrow failure syndrome, or inherited predisposition.
Although allogeneic hematopoietic stem-cell transplantation is the only curative therapy for MDS, mortality after transplantation is high, with deaths attributable to relapsed disease and to . . .
A major recent discovery was the identification of an expansion of a non-coding GGGGCC hexanucleotide repeat in the C9ORF72 gene in patients with frontotemporal dementia and amyotrophic lateral ...sclerosis. Mutations in two other genes are known to account for familial frontotemporal dementia: microtubule-associated protein tau and progranulin. Although imaging features have been previously reported in subjects with mutations in tau and progranulin, no imaging features have been published in C9ORF72. Furthermore, it remains unknown whether there are differences in atrophy patterns across these mutations, and whether regional differences could help differentiate C9ORF72 from the other two mutations at the single-subject level. We aimed to determine the regional pattern of brain atrophy associated with the C9ORF72 gene mutation, and to determine which regions best differentiate C9ORF72 from subjects with mutations in tau and progranulin, and from sporadic frontotemporal dementia. A total of 76 subjects, including 56 with a clinical diagnosis of behavioural variant frontotemporal dementia and a mutation in one of these genes (19 with C9ORF72 mutations, 25 with tau mutations and 12 with progranulin mutations) and 20 sporadic subjects with behavioural variant frontotemporal dementia (including 50% with amyotrophic lateral sclerosis), with magnetic resonance imaging were included in this study. Voxel-based morphometry was used to assess and compare patterns of grey matter atrophy. Atlas-based parcellation was performed utilizing the automated anatomical labelling atlas and Statistical Parametric Mapping software to compute volumes of 37 regions of interest. Hemispheric asymmetry was calculated. Penalized multinomial logistic regression was utilized to create a prediction model to discriminate among groups using regional volumes and asymmetry score. Principal component analysis assessed for variance within groups. C9ORF72 was associated with symmetric atrophy predominantly involving dorsolateral, medial and orbitofrontal lobes, with additional loss in anterior temporal lobes, parietal lobes, occipital lobes and cerebellum. In contrast, striking anteromedial temporal atrophy was associated with tau mutations and temporoparietal atrophy was associated with progranulin mutations. The sporadic group was associated with frontal and anterior temporal atrophy. A conservative penalized multinomial logistic regression model identified 14 variables that could accurately classify subjects, including frontal, temporal, parietal, occipital and cerebellum volume. The principal component analysis revealed similar degrees of heterogeneity within all disease groups. Patterns of atrophy therefore differed across subjects with C9ORF72, tau and progranulin mutations and sporadic frontotemporal dementia. Our analysis suggested that imaging has the potential to be useful to help differentiate C9ORF72 from these other groups at the single-subject level.
Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, ...surprisingly, severe antagonists of ionotropic gamma‐aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a “cloaking” technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two‐photon uncaging microscopy for the first time.
Caged neurotransmitters are known to be antagonistic toward the GABA‐A receptor. Conjugation of a polyester dendrimer “cloak” to the caged compound DEAC450‐GABA significantly decreased its GABA‐A receptor antagonism. The chemical probe was inert at the concentrations required for effective two‐photon photolysis on living cells.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder ...mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.
Display omitted
•A human CLP1 mutation causes brain and motor neuron degeneration•Mutation impairs kinase activity, nuclear localization, and TSEN complex assembly•Patient iNeurons have accumulated pre-tRNA and reduced mature tRNA•Clp1 mutant zebrafish display p53-dependent neurodegeneration
A mutation in the human RNA kinase Clp1 perturbs tRNA biogenesis and promotes susceptibility to apoptosis, leading to a complex neurological phenotype.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD ...heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h
) for European-American females of 29% that is similar to h
for schizophrenia and is substantially higher than h
in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
