Dengue is a mosquito-borne flavivirus that is spreading at an unprecedented rate and has developed into a major health and economic burden in over 50 countries. Even though infected individuals ...develop potent and long-lasting serotype-specific neutralizing antibodies (Abs), the epitopes engaged by human neutralizing Abs have not been identified. Here, we demonstrate that the dengue virus (DENV)-specific serum Ab response in humans consists of a large fraction of cross-reactive, poorly neutralizing Abs and a small fraction of serotype-specific, potently inhibitory Abs. Although many mouse-generated, strongly neutralizing monoclonal antibodies (mAbs) recognize epitopes that are present on recombinant DENV envelope (E) proteins, unexpectedly, the majority of neutralizing Abs in human immune sera bound to intact virions but not to the ectodomain of purified soluble E proteins. These conclusions with polyclonal Abs were confirmed with newly generated human mAbs derived from DENV-immune individuals. Two of three strongly neutralizing human mAbs bound to E protein epitopes that were preserved on the virion but not on recombinant E (rE) protein. We propose that humans produce Abs that neutralize DENV infection by binding a complex, quaternary structure epitope that is expressed only when E proteins are assembled on a virus particle. Mapping studies indicate that this epitope has a footprint that spans adjacent E protein dimers and includes residues at the hinge between domains I and II of E protein. These results have significant implications for the DENV Ab and vaccine field.
An analysis of atmospheric neutrino data from all four run periods of Super-Kamiokande optimized for sensitivity to the neutrino mass hierarchy is presented. Confidence intervals for Δm322, sin2θ23, ...sin2θ13 and δCP are presented for normal neutrino mass hierarchy and inverted neutrino mass hierarchy hypotheses, based on atmospheric neutrino data alone. Additional constraints from reactor data on θ13 and from published binned T2K data on muon neutrino disappearance and electron neutrino appearance are added to the atmospheric neutrino fit to give enhanced constraints on the above parameters. Over the range of parameters allowed at 90% confidence level, the normal mass hierarchy is favored by between 91.9% and 94.5% based on the combined Super-Kamiokande plus T2K result.
The new SARS-CoV-2 Omicron variant (B.1.1.529) has been recently declared a Variant of Concern due to a series of important mutations in the viral spike protein and especially in the receptor-binding ...domain. While investigations into the spread of this new variant are ongoing, the first cases have been detected in Switzerland. Important questions have been raised: (1) Will the PCR assays commonly used to detect SARS-CoV-2 still work for the Omicron variant? (2) Can specific PCR features, e.g. S-gene dropout, be used to identify potential Omicron samples? In this minireview we provide current knowledge on the Omicron variant and guidance on its PCR validation.
Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, ...particularly plasma amyloid-β (Aβ) and Aβ brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aβ and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aβ levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aβ1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aβ from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aβ1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.
An optical network of superconducting quantum bits (qubits) is an appealing platform for quantum communication and distributed quantum computing, but developing a quantum-compatible link between the ...microwave and optical domains remains an outstanding challenge. Operating at T < 100 mK temperatures, as required for quantum electrical circuits, we demonstrate a mechanically mediated microwave–optical converter with 47% conversion efficiency, and use a classical feed-forward protocol to reduce added noise to 38 photons. The feed-forward protocol harnesses our discovery that noise emitted from the two converter output ports is strongly correlated because both outputs record thermal motion of the same mechanical mode. We also discuss a quantum feed-forward protocol that, given high system efficiencies, would allow quantum information to be transferred even when thermal phonons enter the mechanical element faster than the electro-optic conversion rate.
Objective
To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion.
Design
Population‐based ...retrospective observational study.
Setting
Nationwide Inpatient Sample in the USA (2001–2015).
Population
In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies.
Methods
(1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications.
Main outcome measures
Trends, characteristics and complications related to conservative surgery.
Results
Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39–7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62–0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638).
Conclusion
There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications.
Tweetable
Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.
Tweetable
Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.
Abstract
The CHIME/FRB project has detected hundreds of fast radio bursts (FRBs), providing an unparalleled population to statistically probe the foreground media that they illuminate. One such ...foreground medium is the ionized halo of the Milky Way (MW). We estimate the total Galactic electron column density from FRB dispersion measures (DMs) as a function of Galactic latitude using four different estimators, including ones that assume spherical symmetry of the ionized MW halo and ones that imply more latitudinal variation in density. Our observation-based constraints of the total Galactic DM contribution for ∣
b
∣ ≥ 30°, depending on the Galactic latitude and selected model, span 87.8–141 pc cm
−3
. This constraint implies upper limits on the MW halo DM contribution that range over 52–111 pc cm
−3
. We discuss the viability of various gas density profiles for the MW halo that have been used to estimate the halo’s contribution to DMs of extragalactic sources. Several models overestimate the DM contribution, especially when assuming higher halo gas masses (∼3.5 × 10
12
M
⊙
). Some halo models predict a higher MW halo DM contribution than can be supported by our observations unless the effect of feedback is increased within them, highlighting the impact of feedback processes in galaxy formation.
Abstract
We report on the host association of FRB 20181030A, a repeating fast radio burst (FRB) with a low dispersion measure (103.5 pc cm
−3
) discovered by the CHIME/FRB Collaboration et al. Using ...baseband voltage data saved for its repeat bursts, we localize the FRB to a sky area of 5.3 arcmin
2
(90% confidence). Within the FRB localization region, we identify NGC 3252 as the most promising host with an estimated chance-coincidence probability <2.5 × 10
−3
. Moreover, we do not find any other galaxy with
M
r
< −15 AB mag within the localization region to the maximum estimated FRB redshift of 0.05. This rules out a dwarf host 5 times less luminous than any FRB host discovered to date. NGC 3252 is a star-forming spiral galaxy and at a distance of ≈20 Mpc, it is one of the closest FRB hosts discovered thus far. From our archival radio data search, we estimate a 3
σ
upper limit on the luminosity of a persistent compact radio source (source size < 0.3 kpc at 20 Mpc) at 3 GHz to be 2 × 10
26
erg s
−1
Hz
−1
, at least 1500 times smaller than that of the FRB 20121102A persistent radio source. We also argue that a population of young millisecond magnetars alone cannot explain the observed volumetric rate of repeating FRBs. Finally, FRB 20181030A is a promising source for constraining FRB emission models due to its proximity and we strongly encourage its multi-wavelength follow-up.
Soil microbial communities control critical ecosystem processes such as decomposition, nutrient cycling, and soil organic matter formation. Continental scale patterns in the composition and ...functioning of microbial communities are related to climatic, biotic, and edaphic factors such as temperature and precipitation, plant community composition, and soil carbon, nitrogen, and pH. Although these relationships have been well explored individually, the examination of the factors that may act directly on microbial communities vs. those that may act indirectly through other ecosystem properties has not been well developed. To further such understanding, we utilized structural equation modeling (SEM) to evaluate a set of hypotheses about the direct and indirect effects of climatic, biotic, and edaphic variables on microbial communities across the continental United States. The primary goals of this work were to test our current understanding of the interactions among climate, soils, and plants in affecting microbial community composition, and to examine whether variation in the composition of the microbial community affects potential rates of soil enzymatic activities. A model of interacting factors created through SEM shows several expected patterns. Distal factors such as climate had indirect effects on microbial communities by influencing plant productivity, soil mineralogy, and soil pH, but factors related to soil organic matter chemistry had the most direct influence on community composition. We observed that both plant productivity and soil mineral composition were important indirect influences on community composition at the continental scale, both interacting to affect organic matter content and microbial biomass and ultimately community composition. Although soil hydrolytic enzymes were related to the moisture regime and soil carbon, oxidative enzymes were also affected by community composition, reflected in the abundance of soil fungi. These results highlight that soil microbial communities can be modeled within the context of multiple interacting ecosystem properties acting both directly and indirectly on their composition and function, and this provides a rich and informative context with which to examine communities. This work also highlights that variation in climate, microbial biomass, and microbial community composition can affect maximum rates of soil enzyme activities, potentially influencing rates of decomposition and nutrient mineralization in soils.
Abstract
We present results from angular cross correlations between select samples of CHIME/FRB repeaters and galaxies in three photometric galaxy surveys, which have shown correlations with the ...first CHIME/FRB catalog containing repeating and nonrepeating sources: Wide-field Infrared Survey Explorer (WISE) × SCOS, DESI-BGS, and DESI-LRG. We find a statistically significant correlation (
p
-value <0.001, after accounting for look-elsewhere factors) between a sample of repeaters with an extragalactic dispersion measure (DM) > 395 pc cm
−3
and WISE × SCOS galaxies with redshift
z
> 0.275. We demonstrate that the correlation arises surprisingly because of a statistical association between FRB 20200320A (extragalactic DM ≈ 550 pc cm
−3
) and a galaxy group in the same dark matter halo at redshift
z
≈ 0.32. We estimate that the host halo, along with an intervening halo at redshift
z
≈ 0.12, accounts for at least ∼30% of the extragalactic DM. Our results strongly motivate incorporating galaxy group and cluster catalogs into direct host association pipelines for FRBs with
≲
1
′
localization precision, effectively utilizing the two-point information to constrain FRB properties such as their redshift and DM distributions. In addition, we find marginal evidence for a negative correlation at 99.4% confidence limit between a sample of repeating FRBs with baseband data (median extragalactic DM = 354 pc cm
−3
) and DESI-LRG galaxies with redshift 0.3 ≤
z
< 0.45, suggesting that the repeaters might be more prone than apparent nonrepeaters to propagation effects in FRB–galaxy correlations due to intervening free electrons over angular scales ∼0.°5.
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