Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of coronavirus disease 2019 (COVID-19), is readily transmitted person to person. Optimal control of COVID-19 depends on ...directing resources and health messaging to mitigation efforts that are most likely to prevent transmission, but the relative importance of such measures has been disputed.
To assess the proportion of SARS-CoV-2 transmissions in the community that likely occur from persons without symptoms.
This decision analytical model assessed the relative amount of transmission from presymptomatic, never symptomatic, and symptomatic individuals across a range of scenarios in which the proportion of transmission from people who never develop symptoms (ie, remain asymptomatic) and the infectious period were varied according to published best estimates. For all estimates, data from a meta-analysis was used to set the incubation period at a median of 5 days. The infectious period duration was maintained at 10 days, and peak infectiousness was varied between 3 and 7 days (-2 and +2 days relative to the median incubation period). The overall proportion of SARS-CoV-2 was varied between 0% and 70% to assess a wide range of possible proportions.
Level of transmission of SARS-CoV-2 from presymptomatic, never symptomatic, and symptomatic individuals.
The baseline assumptions for the model were that peak infectiousness occurred at the median of symptom onset and that 30% of individuals with infection never develop symptoms and are 75% as infectious as those who do develop symptoms. Combined, these baseline assumptions imply that persons with infection who never develop symptoms may account for approximately 24% of all transmission. In this base case, 59% of all transmission came from asymptomatic transmission, comprising 35% from presymptomatic individuals and 24% from individuals who never develop symptoms. Under a broad range of values for each of these assumptions, at least 50% of new SARS-CoV-2 infections was estimated to have originated from exposure to individuals with infection but without symptoms.
In this decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods, transmission from asymptomatic individuals was estimated to account for more than half of all transmissions. In addition to identification and isolation of persons with symptomatic COVID-19, effective control of spread will require reducing the risk of transmission from people with infection who do not have symptoms. These findings suggest that measures such as wearing masks, hand hygiene, social distancing, and strategic testing of people who are not ill will be foundational to slowing the spread of COVID-19 until safe and effective vaccines are available and widely used.
ABSTRACT
We present a Bayesian full-spectral-fitting analysis of 75 massive ($M_* \gt 10^{10.3} \, \mathrm{M_\odot }$) UVJ-selected galaxies at redshifts of 1.0 < z < 1.3, combining extremely deep ...rest-frame ultraviolet spectroscopy from VANDELS with multiwavelength photometry. By the use of a sophisticated physical plus systematic uncertainties model, constructed within the bagpipes code, we place strong constraints on the star-formation histories (SFHs) of individual objects. We first constrain the stellar mass versus stellar age relationship, finding a steep trend towards earlier average formation time with increasing stellar mass (downsizing) of $1.48^{+0.34}_{-0.39}$ Gyr per decade in mass, although this shows signs of flattening at $M_* \gt 10^{11} \, \mathrm{M_\odot }$. We show that this is consistent with other spectroscopic studies from 0 < z < 2. This relationship places strong constraints on the AGN-feedback models used in cosmological simulations. We demonstrate that, although the relationships predicted by simba and illustristng agree well with observations at z = 0.1, they are too shallow at z = 1, predicting an evolution of ≲0.5 Gyr per decade in mass. Secondly, we consider the connections between green-valley, post-starburst, and quiescent galaxies, using our inferred SFH shapes and the distributions of galaxy physical properties on the UVJ diagram. The majority of our lowest-mass galaxies ($M_* \sim 10^{10.5} \, \mathrm{M_\odot }$) are consistent with formation in recent (z < 2), intense starburst events, with time-scales of ≲500 Myr. A second class of objects experience extended star-formation epochs before rapidly quenching, passing through both green-valley and post-starburst phases. The most massive galaxies in our sample are extreme systems: already old by z = 1, they formed at z ∼ 5 and quenched by z = 3. However, we find evidence for their continued evolution through both AGN and rejuvenated star-formation activity.
In three phase 3 trials, ixekizumab, an anti–IL-17A monoclonal antibody, was effective in the treatment of patients with moderate-to-severe plaque psoriasis. Adverse events included neutropenia, ...candida infections, and inflammatory bowel disease.
Psoriasis is a chronic inflammatory disease that is mediated by aberrant immune responses and driven by self-perpetuating cytokine networks.
1
,
2
Advances in understanding the pathogenic cytokine network of psoriasis have led to the development of new treatments
3
–
5
that provide greater efficacy in terms of complete skin clearance.
6
–
9
The motivation to completely clear psoriasis plaques from the skin of patients has grown in response to accumulating evidence that residual skin disease can affect a patient’s health-related quality of life
10
–
12
similar to that associated with chronic conditions such as type 2 diabetes.
13
Ixekizumab, a recombinant, high-affinity, humanized, IgG4-κ monoclonal . . .
ABSTRACT
While the kinematics of galaxies up to z ∼ 3 have been characterized in detail, only a handful of galaxies at high redshift (z > 4) have been examined in such a way. The Atacama Large ...Millimeter/submillimeter Array (ALMA) Large Program to INvestigate C ii at Early times (ALPINE) survey observed a statistically significant sample of 118 star-forming main-sequence galaxies at z = 4.4–5.9 in C ii158 $\mu$m emission, increasing the number of such observations by nearly 10×. A preliminary qualitative classification of these sources revealed a diversity of kinematic types (i.e. rotators, mergers, and dispersion-dominated systems). In this work, we supplement the initial classification by applying quantitative analyses to the ALPINE data: a tilted ring model (TRM) fitting code (3Dbarolo), a morphological classification (Gini-M20), and a set of disc identification criteria. Of the 75 C ii-detected ALPINE galaxies, 29 are detected at sufficient significance and spatial resolution to allow for TRM fitting and the derivation of morphological and kinematic parameters. These 29 sources constitute a high-mass subset of the ALPINE sample ($M_*\gt 10^{9.5}\, \mathrm{M}_{\odot }$). We robustly classify 14 of these sources (six rotators, five mergers, and three dispersion-dominated systems); the remaining sources showing complex behaviour. By exploring the G-M20 of z > 4 rest-frame far-infrared and C ii data for the first time, we find that our 1 arcsec ∼ 6 kpc resolution data alone are insufficient to separate galaxy types. We compare the rotation curves and dynamical mass profiles of the six ALPINE rotators to the two previously detected z ∼ 4–6 unlensed main-sequence rotators, finding high rotational velocities (∼50–250 km s−1) and a diversity of rotation curve shapes.
ABSTRACT
We study the impact of active galactic nuclei (AGNs) on the CO spectral line energy distribution (SLED) of high-z galaxies. In particular, we want to assess if the CO SLED can be used as a ...probe of AGN activity. To this purpose, we develop a semi-analytical model that takes into account the radiative transfer and the clumpy structure of giant molecular clouds where the CO lines are excited, their distribution in the galaxy disc, and the torus obscuration of the AGN radiation. We study the joint effect on the CO SLED excitation of (i) the X-ray luminosity from the AGNs (LX), (ii) the size of the molecular disc, (iii) the inclination angle (Ω) of the torus with respect to the molecular disc, and (iv) the Giant Molecular Cloud (GMC) mean density. We also discuss the possibility of an enhanced cosmic ray ionization rate (CRIR). We find that the X-ray-dominated region (XDR) generated by the AGNs in every case enhances the CO SLED for J > 5, with increasing excitation of high-J CO lines for increasing X-ray luminosity. Because high-z galaxies are compact, the XDR typically encloses the whole disc, thus its effect can be more important with respect to lower redshift objects. The impact of the XDR can be disentangled from an enhanced CRIR either if $L_\mathrm{ X}\,\gt\, 10^{44} \rm \, erg\, s^{-1}$, or if Ω ≥ 60°. We finally provide predictions on the CO(7–6)/C ii and CO(17–16)/C ii ratios as a function of LX, which can be relevant for ALMA follow-up of galaxies and quasars previously detected in C ii.
Abstract
We present ALMA observations at 107.291 GHz (band 3) and 214.532 GHz (band 6) of GMASS 0953, a star-forming galaxy at z = 2.226 hosting an obscured active galactic nucleus (AGN) that has ...been proposed as a progenitor of compact quiescent galaxies (QGs). We measure for the first time the size of the dust and molecular gas emission of GMASS 0953 that we find to be extremely compact (∼1 kpc). This result, coupled with a very high interstellar medium (ISM) density (n ∼ 105.5 cm−3), a low gas mass fraction (∼0.2), and a short gas depletion time-scale (∼150 Myr), implies that GMASS 0953 is experiencing an episode of intense star formation in its central region that will rapidly exhaust its gas reservoirs, likely aided by AGN-induced feedback, confirming its fate as a compact QG. Kinematic analysis of the CO(6–5) line shows evidence of rapidly rotating gas (Vrot = 320$^{+92}_{-53}$ km s−1), as observed also in a handful of similar sources at the same redshift. On-going quenching mechanisms could either destroy the rotation or leave it intact leading the galaxy to evolve into a rotating QG.
The estimate of stellar metallicities (
Z
*
) of high-
z
galaxies are of paramount importance in order to understand the complexity of dust effects and the reciprocal interrelations among stellar ...mass, dust attenuation, stellar age, and metallicity. Benefiting from uniquely deep far-UV spectra of > 500 star-forming galaxies at redshifts 2 <
z
< 5 extracted from the VANDELS survey and stacked in bins of stellar mass (
M
*
) and UV continuum slope (
β
), we estimate their stellar metallicities
Z
*
from stellar photospheric absorption features at 1501 and 1719 Å, which are calibrated with Starburst99 models and are largely unaffected by stellar age, dust, IMF, nebular continuum, or interstellar absorption. Comparing them to photometric-based spectral slopes in the 1250–1750 Å range, we find that the stellar metallicity increases by ∼0.5 dex from
β
∼ −2 to
β
∼ −1 (1 ≲
A
1600
≲ 3.2), and a dependence with
β
holds at fixed UV absolute luminosity
M
UV
and stellar mass up to ∼10
9.65
M
⊙
. As a result, metallicity is a fundamental ingredient for properly rescaling dust corrections based on
M
UV
and
M
*
. Using the same absorption features, we analyzed the mass-metallicity relation (MZR), and find it to be consistent with the previous VANDELS estimation based on a global fit of the FUV spectra. Similarly, we do not find a significant evolution between
z
∼ 2 and
z
∼ 3.5. Finally, the slopes of our MZR and
Z
*
−
β
relation are in agreement with the predictions of well-studied semi-analytic models (SAM) of galaxy formation, while some tensions remain concerning the absolute metallicity normalization. The relation between the UV slope and stellar metallicity is fundamental to the exploitation of large volume surveys with next-generation telescopes and for the physical characterization of galaxies in the first billion years of our Universe.
We unveil the complex shape of a proto-supercluster at z ∼ 2.45 in the COSMOS field exploiting the synergy of both spectroscopic and photometric redshifts. Thanks to the spectroscopic redshifts of ...the VIMOS Ultra-Deep Survey (VUDS), complemented by the zCOSMOS-Deep spectroscopic sample and high-quality photometric redshifts, we compute the three-dimensional (3D) overdensity field in a volume of ∼100 × 100 × 250 comoving Mpc3 in the central region of the COSMOS field, centred at z ∼ 2.45 along the line of sight. The method relies on a two-dimensional (2D) Voronoi tessellation in overlapping redshift slices that is converted into a 3D density field, where the galaxy distribution in each slice is constructed using a statistical treatment of both spectroscopic and photometric redshifts. In this volume, we identify a proto-supercluster, dubbed “Hyperion” for its immense size and mass, which extends over a volume of ∼60 × 60 × 150 comoving Mpc3 and has an estimated total mass of ∼4.8 × 1015 M⊙. This immensely complex structure contains at least seven density peaks within 2.4 ≲ z ≲ 2.5 connected by filaments that exceed the average density of the volume. We estimate the total mass of the individual peaks, Mtot, based on their inferred average matter density, and find a range of masses from ∼0.1 × 1014 M⊙ to ∼2.7 × 1014 M⊙. By using spectroscopic members of each peak, we obtain the velocity dispersion of the galaxies in the peaks, and then their virial mass Mvir (under the strong assumption that they are virialised). The agreement between Mvir and Mtot is surprisingly good, at less than 1−2σ, considering that (almost all) the peaks are probably not yet virialised. According to the spherical collapse model, these peaks have already started or are about to start collapsing, and they are all predicted to be virialised by redshift z ∼ 0.8−1.6. We finally perform a careful comparison with the literature, given that smaller components of this proto-supercluster had previously been identified using either heterogeneous galaxy samples (Lyα emitters, sub-mm starbursting galaxies, CO emitting galaxies) or 3D Lyα forest tomography on a smaller area. With VUDS, we obtain, for the first time across the central ∼1 deg2 of the COSMOS field, a panoramic view of this large structure, that encompasses, connects, and considerably expands in a homogeneous way on all previous detections of the various sub-components. The characteristics of this exceptional proto-supercluster, its redshift, its richness over a large volume, the clear detection of its sub-components, together with the extensive multi-wavelength imaging and spectroscopy granted by the COSMOS field, provide us the unique possibility to study a rich supercluster in formation.
•Astrocyte functions are altered during aging and in response to Alzheimer’s Disease and Multiple Sclerosis.•Astrocytes have beneficial and detrimental effects on neurons and oligodendrocytes during ...disease.•Understanding these effects can lead to the use of astrocytes as therapeutic targets.
Astrocytes are traditionally recognized for their multiple roles in support of brain function. However, additional changes in these roles are evident in response to brain diseases. In this review, we highlight positive and negative effects of astrocytes in response to aging, Alzheimer’s disease and Multiple Sclerosis. We summarize data suggesting that reactive astrocytes may perform critical functions that might be relevant to the etiology of these conditions. In particular, we relate astrocytes effects to actions on synaptic transmission, cognition, and myelination. We suggest that a better understanding of astrocyte functions and how these become altered in response to aging or disease will lead to the appreciation of these cells as useful therapeutic targets.
Immunological approaches to HIV cure Ward, Adam R.; Mota, Talia M.; Jones, R. Brad
Seminars in immunology,
January 2021, 2021-01-00, 20210101, Letnik:
51
Journal Article
Recenzirano
Odprti dostop
•HIV infection persists despite antiviral responses and antiretroviral therapy.•Rare individuals can naturally control HIV infection by immune-mediated mechanisms.•HIV cures could be functional ...(durable remission) or sterilizing (eradication).•Immunotherapies to cure HIV could harness and enhance T-cell and B-cell responses.•Combination immunotherapies are most likely to succeed in achieving an HIV cure.
Combination antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV) infection has proven remarkably successful – for those who can access and afford it – yet HIV infection persists indefinitely in a reservoir of cells, despite effective ART and despite host antiviral immune responses. An HIV cure is therefore the next aspirational goal and challenge, though approaches differ in their objectives – with ‘functional cures’ aiming for durable viral control in the absence of ART, and ‘sterilizing cures’ aiming for the more difficult to realize objective of complete viral eradication. Mechanisms of HIV persistence, including viral latency, anatomical sequestration, suboptimal immune functioning, reservoir replenishment, target cell-intrinsic immune resistance, and, potentially, target cell distraction of immune effectors, likely need to be overcome in order to achieve a cure. A small fraction of people living with HIV (PLWH) naturally control infection via immune-mediated mechanisms, however, providing both sound rationale and optimism that an immunological approach to cure is possible. Herein we review up to date knowledge and emerging evidence on: the mechanisms contributing to HIV persistence, as well as potential strategies to overcome these barriers; promising immunological approaches to achieve viral control and elimination of reservoir-harboring cells, including harnessing adaptive immune responses to HIV and engineered therapies, as well as enhancers of their functions and of complementary innate immune functioning; and combination strategies that are most likely to succeed. Ultimately, a cure must be safe, effective, durable, and, eventually, scalable in order to be widely acceptable and available.
PDF
