Role of vascular smooth muscle cell clonality in atherosclerosis

Atherosclerotic cardiovascular disease remains the leading cause of death worldwide. While many cell types contribute to the growing atherosclerotic plaque, the vascular smooth muscle cell (SMC) is a major contributor due in part to its remarkable plasticity and ability to undergo phenotype switching in response to injury. SMCs can migrate into the fibrous cap, presumably stabilizing the plaque, or accumulate within the lesional core, possibly accelerating vascular inflammation. How SMCs expand and react to disease stimuli has been a controversial topic for many decades. While early studies relying on X-chromosome inactivation were inconclusive due to low resolution and sensitivity, recent advances in multi-color lineage tracing models have revitalized the concept that SMCs likely expand in an oligoclonal fashion during atherogenesis. Current efforts are focused on determining whether all SMCs have equal capacity for clonal expansion or if a “stem-like” progenitor cell may exist, and to understand how constituents of the clone decide which phenotype they will ultimately adopt as the disease progresses. Mechanistic studies are also beginning to dissect the processes which confer cells with their overall survival advantage, test whether these properties are attributable to intrinsic features of the expanding clone, and define the role of cross-talk between proliferating SMCs and other plaque constituents such as neighboring macrophages. In this review, we aim to summarize the historical perspectives on SMC clonality, highlight unanswered questions, and identify translational issues which may need to be considered as therapeutics directed against SMC clonality are developed as a novel approach to targeting atherosclerosis

Do we need to rethink the diagnoses melanoma in situ and severely dysplastic naevus?

Many countries have seen a dramatic increase in the reported incidence of cutaneous melanoma in recent decades, largely driven by increased diagnoses of melanoma in situ and thin invasive melanoma. The incidence of thick and metastatic melanomas, and melanoma mortality have remained relatively stable. While aging populations could be causing some true increase in melanoma incidence, much of this increase may represent overdiagnosis: diagnosis of lesions that would never have caused harm if left undetected and untreated. If it occurs, melanoma overdiagnosis may result in potential psychological and physical harms to individuals, as well as significant cost to the healthcare system from procedures and long-term surveillance. The use of new diagnostic labels (e.g. “melanocytic neoplasm”) and/or the recalibration of diagnostic thresholds for the diagnosis of melanoma in situ could reduce these harms

First Look at z > 1 Bars in the Rest-Frame Near-Infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of {\it{JWST}} CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at $z>1$ based on rest-frame NIR F444W images of high resolution (~1.3 kpc at z ~ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at $z>1$ with spectroscopic redshifts, including the two highest redshift bars at ~2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at $z$ ~ 1.1-2.3 presented in our study have projected semi-major axes of ~2.9-4.3 kpc and projected ellipticities of ~0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ~ $1 \times 10^{10}$ to $2 \times 10^{11}$ $M_{\odot}$, star formation rates of ~ 21-295 $M_{\odot}$ yr$^{-1}$, and several have potential nearby companions. Our finding of bars at $z$ ~1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-10 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ~ 0.Comment: 16 pages, 5 figures. Accepted for Publication in Astrophysical Journal Letter

CEERS Key Paper. V. Galaxies at 4 < z < 9 Are Bluer than They Appear-Characterizing Galaxy Stellar Populations from Rest-frame ∼1 μm Imaging

We present results from the Cosmic Evolution Early Release Survey on the stellar population parameters for 28 galaxies with redshifts 4 &lt; z &lt; 9 using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 μm data extend the coverage of the rest-frame spectral energy distribution to nearly 1 μm for galaxies in this redshift range. By modeling the galaxies’ SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 Å)—I-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower ratios of stellar mass to light. The MIRI data reduce the stellar masses by 〈 Δ log M * 〉 = 0.25 dex at 4 &lt; z &lt; 6 and 0.37 dex at 6 &lt; z &lt; 9. This also reduces the star formation rates (SFRs) by 〈ΔlogSFR〉 = 0.14 dex at 4 &lt; z &lt; 6 and 0.27 dex at 6 &lt; z &lt; 9. The MIRI data also improve constraints on the allowable stellar mass formed in early star formation. We model this using a star formation history that includes both a “burst” at z f = 100 and a slowly varying (“delayed-τ”) model. The MIRI data reduce the allowable stellar mass by 0.6 dex at 4 &lt; z &lt; 6 and by ≈1 dex at 6 &lt; z &lt; 9. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early Universe (z ≈ 9). Therefore, observations of rest-frame ≳1 μm are paramount for constraining the stellar-mass buildup in galaxies at very high redshifts.</p

CEERS Key Paper IV: Galaxies at 4<z<94 < z < 9 are Bluer than They Appear -- Characterizing Galaxy Stellar Populations from Rest-Frame ∼1\sim 1 micron Imaging

We present results from the Cosmic Evolution Early Release Survey (CEERS) on the stellar-population parameters for 28 galaxies with redshifts $4<z<9$ using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 $\mu$m data extend the coverage of the rest-frame spectral-energy distribution (SED) to nearly 1 micron for galaxies in this redshift range. By modeling the galaxies' SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 \r{A}) $-$ $I$-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower (stellar)-mass-to-light ratios. The MIRI data reduce the stellar masses by $\langle \Delta\log M_\ast\rangle=0.25$ dex at $4<z<6$ (a factor of 1.8) and 0.37 dex at $6<z<9$ (a factor of 2.3). This also reduces the star-formation rates (SFRs) by $\langle \Delta\log\mathrm{SFR} \rangle=0.14$ dex at $4<z<6$ and 0.27 dex at $6<z<9$. The MIRI data also improve constraints on the allowable stellar mass formed in early star-formation. We model this using a star-formation history that includes both a "burst' at $z_f=100$ and a slowly varying ("delayed-$\tau$") model. The MIRI data reduce the allowable stellar mass by 0.6 dex at $4<z< 6$ and by $\approx$1 dex at $6<z<9$. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early universe ($z\approx9$). Therefore, observations of rest-frame $\gtrsim$1 $\mu$m are paramount for constraining the stellar-mass build-up in galaxies at very high-redshifts.Comment: Updated with accepted ApJ version. Part of the CEERS Focus Issue. 27 pages, many figures (4 Figure Sets, available upon reasonable request

CEERS Key Paper V: A triality on the nature of HST-dark galaxies

The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR faint, mid-IR bright sources, HST-dark galaxies among them. We gather JWST data from the CEERS survey in the EGS, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions (SEDs) to estimate both photometric redshifts in 2 dimensions and stellar populations properties in a pixel-by-pixel basis. We select 138 galaxies with F150W-F356W>1.5 mag, F356W<27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies at 2<z<6 with masses 9<log M/M_sun<11 and a variety of specific SFRs (100 Gyr^-1); (2) 18% are quiescent/dormant (i.e., subject to reignition and rejuvenation) galaxies at 3<z<5, masses log M/M_sun~10 and post-starburst stellar mass-weighted ages (0.5-1 Gyr); and (3) 11% are strong young starbursts with indications of high-EW emission lines (typically, [OIII]+Hbeta) at 6<z<7 and log M/M_sun~9.5. The sample is dominated by disk-like galaxies with a remarkable compactness for XELG-z6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2<A(V)<5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A(V)~0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and sub-millimeter galaxies. This study implies high levels of star formation activity between z~20 and z~10, where virtually 100% of our galaxies had already formed 10^8 M_sun of their stellar content, 60% of them had assembled 10^9 M_sun, and 10% up to 10^10 M_sun (in situ or ex situ). (abridged)Comment: Published in CEERS ApJL Focus Issue, ApJL 946, L1

Galaxies Going Bananas: Inferring the 3D Geometry of High-Redshift Galaxies with JWST-CEERS

The 3D geometry of high-redshift galaxies remains poorly understood. We build a differentiable Bayesian model and use Hamiltonian Monte Carlo to efficiently and robustly infer the 3D shapes of star-forming galaxies in JWST-CEERS observations with $\log M_*/M_{\odot}=9.0-10.5$ at $z=0.5-8.0$. We reproduce previous results from HST-CANDELS in a fraction of the computing time and constrain the mean ellipticity, triaxiality, size and covariances with samples as small as $\sim50$ galaxies. We find high 3D ellipticities for all mass-redshift bins suggesting oblate (disky) or prolate (elongated) geometries. We break that degeneracy by constraining the mean triaxiality to be $\sim1$ for $\log M_*/M_{\odot}=9.0-9.5$ dwarfs at $z>1$ (favoring the prolate scenario), with significantly lower triaxialities for higher masses and lower redshifts indicating the emergence of disks. The prolate population traces out a ``banana'' in the projected $b/a-\log a$ diagram with an excess of low $b/a$, large $\log a$ galaxies. The dwarf prolate fraction rises from $\sim25\%$ at $z=0.5-1.0$ to $\sim50-80\%$ at $z=3-8$. If these are disks, they cannot be axisymmetric but instead must be unusually oval (triaxial) unlike local circular disks. We simultaneously constrain the 3D size-mass relation and its dependence on 3D geometry. High-probability prolate and oblate candidates show remarkably similar S\'ersic indices ($n\sim1$), non-parametric morphological properties and specific star formation rates. Both tend to be visually classified as disks or irregular but edge-on oblate candidates show more dust attenuation. We discuss selection effects, follow-up prospects and theoretical implications.Comment: Submitted to ApJ, main body is 35 pages of which ~half are full-page figures, comments welcom

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

The Global Burden of Diseases, Injuries and Risk Factors 2017 includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. METHODS: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting