Two placebo-controlled trials involving pregnant women with subclinical hypothyroidism or hypothyroxinemia showed that levothyroxine beginning between 8 and 20 weeks of gestation did not ...significantly improve cognitive outcomes in children through 5 years of age.
Observational studies spanning almost three decades suggest that subclinical thyroid disease during pregnancy is associated with adverse outcomes.
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–
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In 1999, interest in undiagnosed maternal thyroid dysfunction was heightened by studies suggesting an association between subclinical thyroid hypofunction and impaired fetal neuropsychological development.
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,
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In one report, children of women whose serum thyrotropin levels during pregnancy were greater than the 98th percentile had a lower IQ than children of matched controls who had a normal thyrotropin level.
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In another study, children whose mothers had a serum free thyroxine (T
4
) level of less than the 10th percentile in early . . .
Obtaining a burning plasma is a critical step towards self-sustaining fusion energy
. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, ...which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule
through two different implosion concepts
. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics
. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.
Abstract
Plate tectonics and mantle dynamics necessitate mantle recycling throughout Earth’s history, yet direct geochemical evidence for mantle reprocessing remains elusive. Here we present evidence ...of recycled supra-subduction zone mantle wedge peridotite dredged from the Mid-Atlantic Ridge near 16°30′N. Peridotite trace-element characteristics are inconsistent with fractional anhydrous melting typically associated with a mid-ocean ridge setting. Instead, the samples are best explained by hydrous flux melting which changed the melting reactions such that clinopyroxene was not exhausted at high degrees of melting and was retained in the residuum. Based on along-axis ridge depth variations, this buoyant refractory arc mantle is likely compensated at depth by denser, likely garnet-rich, lithologies within the mantle column. Our results suggest that highly refractory arc mantle relicts are entrained in the upper mantle and may constitute >60% of the upper mantle by volume. These highly refractory mantle domains, which contribute little to mantle melting, are under-represented in compilations of mantle composition that rely on inverted basalt compositions alone.
Abstract
In a burning plasma state
1–7
, alpha particles from deuterium–tritium fusion reactions redeposit their energy and are the dominant source of heating. This state has recently been achieved ...at the US National Ignition Facility
8
using indirect-drive inertial-confinement fusion. Our experiments use a laser-generated radiation-filled cavity (a hohlraum) to spherically implode capsules containing deuterium and tritium fuel in a central hot spot where the fusion reactions occur. We have developed more efficient hohlraums to implode larger fusion targets compared with previous experiments
9,10
. This delivered more energy to the hot spot, whereas other parameters were optimized to maintain the high pressures required for inertial-confinement fusion. We also report improvements in implosion symmetry control by moving energy between the laser beams
11–16
and designing advanced hohlraum geometry
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that allows for these larger implosions to be driven at the present laser energy and power capability of the National Ignition Facility. These design changes resulted in fusion powers of 1.5 petawatts, greater than the input power of the laser, and 170 kJ of fusion energy
18,19
. Radiation hydrodynamics simulations
20,21
show energy deposition by alpha particles as the dominant term in the hot-spot energy balance, indicative of a burning plasma state.
ABSTRACT
Open clusters are unique tracers of the history of our own Galaxy’s disc. According to our membership analysis based on Gaia astrometry, out of the 226 potential clusters falling in the ...footprint of the GALactic Archaeology with HERMES (GALAH) survey or the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey, we find that 205 have secure members that were observed by at least one of the surveys. Furthermore, members of 134 clusters have high-quality spectroscopic data that we use to determine their chemical composition. We leverage this information to study the chemical distribution throughout the Galactic disc of 21 elements, from C to Eu. The radial metallicity gradient obtained from our analysis is −0.076 ± 0.009 dex kpc−1, which is in agreement with previous works based on smaller samples. Furthermore, the gradient in the Fe/H–guiding radius (rguid) plane is −0.073 ± 0.008 dex kpc−1. We show consistently that open clusters trace the distribution of chemical elements throughout the Galactic disc differently than field stars. In particular, at the given radius, open clusters show an age–metallicity relation that has less scatter than field stars. As such scatter is often interpreted as an effect of radial migration, we suggest that these differences are due to the physical selection effect imposed by our Galaxy: clusters that would have migrated significantly also had higher chances to get destroyed. Finally, our results reveal trends in the X/Fe–rguid–age space, which are important to understand production rates of different elements as a function of space and time.
Cross-sectional observational studies suggest that between 50% and 60% of patients misuse a dry powder inhaler, whereas studies with electronic monitors indicate that patients sometimes ...overuse/underuse their inhalers. It is not known what impact errors and erratic use have on inhaler adherence.
The purpose of this study was to longitudinally quantify when and how patients adhered to a twice-daily preventer treatment by using a novel acoustic recording device attached to an inhaler (INhaler Compliance Assessment).
Patients with a history of asthma or chronic obstructive pulmonary disease (n = 123) from primary care and community pharmacies were given an INhaler Compliance Assessment-adapted inhaler for 1 month. Analysis of the audio files provided quantitative information on time and technique of inhaler use.
Data were available for 103 patients. Twenty-one patients (20%) used their inhaler in the correct manner at the correct interval. There were 5045 audio files with attempted inhalations, of which 1204 had technique errors (24%). Errors included inadequate flow (27%), drug priming without inhalation (19%), exhalation into the inhaler (18%), and multiple inhalations (25%). On average, participants made errors 20% of the time. Of 60 doses expected to be taken in a month per person, on average 49 doses (82%) were attempted and when errors were accounted for, the average number of actual doses taken was 34 doses (57%; P < .01) comparing attempted to actual doses.
These data highlight that ineffective and irregular inhaler use is common and when combined in a single calculation indicate that only 20% of participants used their inhaler correctly and on time.
Safe and effective coronavirus disease-19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may ...improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged nonhuman primates (NHPs). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared with a single dose. In one-dose regimens, neutralizing antibody responses were stable for at least 14 wk, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and T helper cell (Th cell) 1-skewed cellular responses in aged NHPs that were comparable to those in adult animals. Aged Ad26.COV2.S-vaccinated animals challenged 3 mo after dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. Neutralization of variants of concern by NHP sera was reduced for B.1.351 lineages while maintained for the B.1.1.7 lineage independent of Ad26.COV2.S vaccine regimen.
ABSTRACT
Fast-rotating pulsars and magnetars have been suggested as the central engines of superluminous supernovae (SLSNe) and fast radio bursts, and this scenario naturally predicts non-thermal ...synchrotron emission from their nascent pulsar wind nebulae (PWNe). We report results of high-frequency radio observations with ALMA and NOEMA for three SLSNe (SN 2015bn, SN 2016ard, and SN 2017egm), and present a detailed theoretical model to calculate non-thermal emission from PWNe with an age of ∼1−3 yr. We find that the ALMA data disfavours a PWN model motivated by the Crab nebula for SN 2015bn and SN 2017egm, and argue that this tension can be resolved if the nebular magnetization is very high or very low. Such models can be tested by future MeV–GeV gamma-ray telescopes such as AMEGO.
•Self-adjuvanting, self-assembling protein nanoparticle to prevent malaria is made.•Amounts of selected domains of flagellin per nanoparticle are optimized.•Immune responses and protective efficacy ...of the vaccine are determined.
To eliminate the problems associated with the use of extraneous adjuvants we have designed a Self-Assembling Protein Nanoparticle (SAPN) containing epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) (designated FMP014) and portions of the TLR5 agonist flagellin (designated FMP014D0D1) as an intrinsic adjuvant. By combining different molar ratios of FMP014 to FMP014D0D1 monomers before self-assembly, we generated multiple nanoparticles and investigated their biophysical characteristics, immunogenicity and protective efficacy. Immunization with the construct formulated with the ratio 58:2 of FMP014 to FMP014D0D1 had the highest protective efficacy against a challenge with a transgenic P. berghei sporozoite expressing PfCSP. Increasing the proportion of flagellin per particle resulted in an inverse relationship with levels of both antibody titers and protection. The cytokine profiles of the various immunization groups were evaluated and quantitative amounts of the cytokines IL-2, IFN-γ, IL-12/p70 (Th1); IL4, IL5 (Th2); TNF-α, IL1β, IL-6, KC/GRO (pro-inflammatory), and IL-10 (immunomodulatory) were measured. The relationship of the cytokines to each other revealed a strong immunomodulatory effect depending on the proportion of flagellin in the construct. Our results demonstrate that SAPNs with flagellin may be a promising strategy for the development and delivery of a safe vaccine for infectious diseases.
Each year in the United States, approximately 250,000 infants are born weighing less than 2500 g. These infants are classified as having low birth weight.
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Although the majority of these infants are ...born before term, approximately 40,000 are born at term according to National Institutes of Health estimates, having suffered intrauterine growth retardation.
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In 1963 Lubchenco and coworkers
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published detailed birth-weight nomograms according to gestational week. Small-for-gestational-age infants were subsequently defined as those whose weights were below the 10th percentile for their gestational ages.
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These infants were found to be at increased risk for neonatal death. For example, the neonatal . . .
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