Background and purpose
Hypertension (HTN) is a common comorbidity in multiple sclerosis (MS), and it significantly contributes to adverse outcomes. Unfortunately, the distribution of HTN in persons ...with MS has not been well characterized, and prior estimates have primarily relied on modest sample sizes. The objective of this study was to robustly describe the distribution of HTN in the MS population in comparison to the non‐MS population with considerations for age, sex, and race. To date, this is the largest investigation of its kind.
Methods
We conducted a cross‐sectional study of 37 million unique electronic health records available in the IBM Explorys Enterprise Performance Management: Explore database (Explorys) spanning the United States. This resource has previously been validated for use in MS. We evaluated the prevalence of HTN in MS (N = 122 660) and non‐MS (N = 37 075 350) cohorts, stratifying by age, sex, and race.
Results
The prevalence of HTN was significantly greater among those with MS than among those without MS across age, sex, and race subpopulations, even after adjusting for age and sex. HTN was 25% more common in MS. In both MS and non‐MS cohorts, the prevalence of HTN progressively increased with age and was higher in Black Americans and in males.
Discussion
This study demonstrated that HTN is significantly more common in the MS population compared to the non‐MS population, irrespective of sex and race. Because HTN is the leading global risk factor for disability and death, these results emphasize the need for aggressive screening for, and management of, HTN in the MS population.
The age‐, sex‐, and race‐adjusted prevalence of hypertension is 25% higher in multiple sclerosis (MS) patients than non‐MS patients. This elevated age‐ and sex‐adjusted burden of hypertension is irrespective of being Black (23% higher) or White (25%) American.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Using the Murchison Widefield Array (MWA), the low-frequency Square Kilometre Array precursor located in Western Australia, we have completed the GaLactic and Extragalactic All-sky MWA (GLEAM) ...survey, and present the resulting extragalactic catalogue, utilizing the first year of observations. The catalogue covers 24 831 square degrees, over declinations south of +30... and Galactic latitudes outside 10... of the Galactic plane, excluding some areas such as the Magellanic Clouds. It contains 307 455 radio sources with 20 separate flux density measurements across 72-231 MHz, selected from a time- and frequency-integrated image centred at 200 MHz, with a resolution of ...2 arcmin. Over the catalogued region, we estimate that the catalogue is 90 per cent complete at 170 mJy, and 50 per cent complete at 55 mJy, and large areas are complete at even lower flux density levels. Its reliability is 99.97 per cent above the detection threshold of 5..., which itself is typically 50 mJy. These observations constitute the widest fractional bandwidth and largest sky area survey at radio frequencies to date, and calibrate the low-frequency flux density scale of the southern sky to better than 10 per cent. This paper presents details of the flagging, imaging, mosaicking and source extraction/characterization, as well as estimates of the completeness and reliability. All source measurements and images are available online. This is the first in a series of publications describing the GLEAM survey results. (ProQuest: ... denotes formulae/symbols omitted.)
ABSTRACT The Murchison Widefield Array (MWA) has collected hundreds of hours of Epoch of Reionization (EoR) data and now faces the challenge of overcoming foreground and systematic contamination to ...reduce the data to a cosmological measurement. We introduce several novel analysis techniques, such as cable reflection calibration, hyper-resolution gridding kernels, diffuse foreground model subtraction, and quality control methods. Each change to the analysis pipeline is tested against a two-dimensional power spectrum figure of merit to demonstrate improvement. We incorporate the new techniques into a deep integration of 32 hours of MWA data. This data set is used to place a systematic-limited upper limit on the cosmological power spectrum of mK2 at k = 0.27 h Mpc−1 and z = 7.1, consistent with other published limits, and a modest improvement (factor of 1.4) over previous MWA results. From this deep analysis, we have identified a list of improvements to be made to our EoR data analysis strategies. These improvements will be implemented in the future and detailed in upcoming publications.
•Six serum metabolites were predictive for MS in males.•Results support lipidomic changes in MS.•Several MS risk variants were associated with the top predictive metabolites.•Pathways analyses ...suggest processes involved in MS pathology.
Diagnostic delays are common for multiple sclerosis (MS) since diagnosis typically depends on the presentation of nonspecific clinical symptoms together with radiologically-determined central nervous system (CNS) lesions. It is important to reduce diagnostic delays as earlier initiation of disease modifying therapies mitigates long-term disability. Developing a metabolomic blood-based MS biomarker is attractive, but prior efforts have largely focused on specific subsets of metabolite classes or analytical platforms. Thus, there are opportunities to interrogate metabolite profiles using more expansive and comprehensive approaches for developing MS biomarkers and for advancing our understanding of MS pathogenesis.
To identify putative blood-based MS biomarkers, we comprehensively interrogated the metabolite profiles in 12 non-Hispanic white, non-smoking, male MS cases who were drug naïve for 3 months prior to biospecimen collection and 13 non-Hispanic white, non-smoking male controls who were frequency matched to cases by age and body mass index. We performed untargeted two-dimensional gas chromatography and time-of-flight mass spectrometry (GCxGC-TOFMS) and targeted lipidomic and amino acid analysis on serum. 325 metabolites met quality control and supervised machine learning was used to identify metabolites most informative for MS status. The discrimination potential of these select metabolites were assessed using receiver operator characteristic curves based on logistic models; top candidate metabolites were defined as having area under the curves (AUC) >80%. The associations between whole-genome expression data and the top candidate metabolites were examined, followed by pathway enrichment analyses. Similar associations were examined for 175 putative MS risk variants and the top candidate metabolites.
12 metabolites were determined to be informative for MS status, of which 6 had AUCs >80%: pyroglutamate, laurate, acylcarnitine C14:1, N-methylmaleimide, and 2 phosphatidylcholines (PC ae 40:5, PC ae 42:5). These metabolites participate in glutathione metabolism, fatty acid metabolism/oxidation, cellular membrane composition, and transient receptor potential channel signaling. Pathway analyses based on the gene expression association for each metabolite suggested enrichment for pathways associated with apoptosis and mitochondrial dysfunction. Interestingly, the predominant MS genetic risk allele HLA-DRB1×15:01 was associated with one of the 6 top metabolites.
Our analysis represents the most comprehensive description of metabolic changes associated with MS in serum, to date, with the inclusion of genomic and genetic information. We identified atypical metabolic processes that differed between MS patients and controls, which may enable the development of biological targets for diagnosis and treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report results from a programme aimed at investigating the temperature of neutral gas in high-redshift damped Lyman α absorbers (DLAs). This involved (1) H i 21 cm absorption studies of a large ...sample of DLAs towards radio-loud quasars, (2) very long baseline interferometric studies to measure the low-frequency quasar core fractions, and (3) optical/ultraviolet spectroscopy to determine DLA metallicities and the velocity widths of low-ionization metal lines. Including literature data, our sample consists of 37 DLAs with estimates of the harmonic mean spin temperature T
s. We find a statistically significant (4σ) difference between the T
s distributions in the high-z (z > 2.4) and low-z (z < 2.4) DLA samples. The high-z sample contains more systems with high spin temperature, T
s 1000 K. The T
s distributions in DLAs and the Galaxy are also significantly ( 6σ) different, with more high-T
s sightlines in DLAs than in the Milky Way. The high T
s values in the high-z DLAs of our sample arise due to low fractions of the cold neutral medium (CNM). Only 2 of 23 DLAs at z > 1.7 have T
s values indicating CNM fractions >20 per cent, comparable to the median value ( 27 per cent) in the Galaxy. We tested whether the H i column density measured towards the optical quasar might be systematically different from that towards the radio core by comparing the H i column densities inferred from H i 21 cm emission studies at different spatial resolutions ( 15 pc-1 kpc) in the Large Magellanic Cloud. The high-resolution N
H i
values are, on average, larger than the smoothed ones for N
H i
> 1021 cm−2, but lower than the smoothed N
H i
estimates for N
H i
< 1021 cm−2. Since there are far more DLAs with low N
H i
values than high ones, the use of the optical N
H i
value for the radio sightline results in a statistical tendency to underestimate DLA spin temperatures. For 29 DLAs with metallicity estimates, we confirm the presence of an anticorrelation between T
s and metallicity Z/H, at 3.5σ significance via a non-parametric Kendall-tau test. This result was obtained with the assumption that the DLA covering factor is equal to the core fraction. However, Monte Carlo simulations show that the significance of the result is only marginally decreased if the covering factor and the core fraction are uncorrelated, or if there is a random error in the inferred covering factor. We also find statistically significant evidence for redshift evolution in DLA spin temperatures even for the DLA sub-sample at z > 1. Since all DLAs at z > 1 have angular diameter distances comparable to or larger than those of their background quasars, they have similar efficiency in covering the quasars. We conclude that low covering factors in high-z DLAs cannot account for the observed redshift evolution in spin temperatures.
ABSTRACT Detection of the cosmological neutral hydrogen signal from the Epoch of Reionization (EoR) and estimation of its basic physical parameters are principal scientific aims of many current ...low-frequency radio telescopes. Here we describe the Cosmological H i Power Spectrum Estimator (CHIPS), an algorithm developed and implemented with data from the Murchison Widefield Array, to compute the two-dimensional and spherically-averaged power spectrum of brightness temperature fluctuations. The principal motivations for CHIPS are the application of realistic instrumental and foreground models to form the optimal estimator, thereby maximizing the likelihood of unbiased signal estimation, and allowing a full covariant understanding of the outputs. CHIPS employs an inverse-covariance weighting of the data through the maximum likelihood estimator, thereby allowing use of the full parameter space for signal estimation ("foreground suppression"). We describe the motivation for the algorithm, implementation, application to real and simulated data, and early outputs. Upon application to a set of 3 hr of data, we set a 2 upper limit on the EoR dimensionless power at Mpc−1 of mK2 in the redshift range z = 6.2-6.6, consistent with previous estimates.
We present first results from radio observations with the Murchison Widefield Array seeking to constrain the power spectrum of 21 cm brightness temperature fluctuations between the redshifts of 11.6 ...and 17.9 (113 and 75 MHz). 3 h of observations were conducted over two nights with significantly different levels of ionospheric activity. We use these data to assess the impact of systematic errors at low frequency, including the ionosphere and radio-frequency interference, on a power spectrum measurement. We find that after the 1–3 h of integration presented here, our measurements at the Murchison Radio Observatory are not limited by RFI, even within the FM band, and that the ionosphere does not appear to affect the level of power in the modes that we expect to be sensitive to cosmology. Power spectrum detections, inconsistent with noise, due to fine spectral structure imprinted on the foregrounds by reflections in the signal-chain, occupy the spatial Fourier modes where we would otherwise be most sensitive to the cosmological signal. We are able to reduce this contamination using calibration solutions derived from autocorrelations so that we achieve an sensitivity of 104 mK on comoving scales k ≲ 0.5 h Mpc−1. This represents the first upper limits on the 21 cm power spectrum fluctuations at redshifts 12 ≲ z ≲ 18 but is still limited by calibration systematics. While calibration improvements may allow us to further remove this contamination, our results emphasize that future experiments should consider carefully the existence of and their ability to calibrate out any spectral structure within the EoR window.
Data suggest that clinical applications of human induced pluripotent stem cells (hiPSCs) will be realized. Nonetheless, clinical applications will require hiPSCs that are free of exogenous DNA and ...that can be manufactured through Good Manufacturing Practice (GMP). Optimally, derivation of hiPSCs should be rapid and efficient in order to minimize manipulations, reduce potential for accumulation of mutations and minimize financial costs. Previous studies reported the use of modified synthetic mRNAs to reprogram fibroblasts to a pluripotent state. Here, we provide an optimized, fully chemically defined and feeder-free protocol for the derivation of hiPSCs using synthetic mRNAs. The protocol results in derivation of fully reprogrammed hiPSC lines from adult dermal fibroblasts in less than two weeks. The hiPSC lines were successfully tested for their identity, purity, stability and safety at a GMP facility and cryopreserved. To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have detected the four 18 cm OH lines from the z approximaetely 0.765 gravitational lens toward PMN J0134-0931. The 1612 and 1720 MHz lines are in conjugate absorption and emission, providing a ...laboratory to test the evolution of fundamental constants over a large lookback time. We compare the HI and OH main line absorption redshifts of the different components in the z approximately 0.765 absorber and the z approximately 0.685 lens toward B0218 + 357 to place stringent constraints on changes in F triple-bond g(p)alpha(2)/mu(1.57). We obtain DeltaF/F = (0.44 +/- 0.36(stat) +/- 1.0(sys)t) x 10(-5), consistent with no evolution over the redshift range 0 < z < or = 0.7. The measurements have a 2sigma sensitivity of Deltaalpha/alpha < 6.7 x 10(-6) or Deltamu/mu < 1.4 x 10(-5) to fractional changes in alpha and mu over a period of approximately 6.5 G yr, half the age of the Universe. These are among the most sensitive constraints on changes in mu.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
ABSTRACT Detection of 21 cm emission of H i from the epoch of reionization, at redshifts , is limited primarily by foreground emission. We investigate the signatures of wide-field measurements and an ...all-sky foreground model using the delay spectrum technique that maps the measurements to foreground object locations through signal delays between antenna pairs. We demonstrate interferometric measurements are inherently sensitive to all scales, including the largest angular scales, owing to the nature of wide-field measurements. These wide-field effects are generic to all observations but antenna shapes impact their amplitudes substantially. A dish-shaped antenna yields the most desirable features from a foreground contamination viewpoint, relative to a dipole or a phased array. Comparing data from recent Murchison Widefield Array observations, we demonstrate that the foreground signatures that have the largest impact on the H i signal arise from power received far away from the primary field of view. We identify diffuse emission near the horizon as a significant contributing factor, even on wide antenna spacings that usually represent structures on small scales. For signals entering through the primary field of view, compact emission dominates the foreground contamination. These two mechanisms imprint a characteristic pitchfork signature on the "foreground wedge" in Fourier delay space. Based on these results, we propose that selective down-weighting of data based on antenna spacing and time can mitigate foreground contamination substantially by a factor of ∼100 with negligible loss of sensitivity.
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