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Lyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts (z ≲ 7) may also mimic the near-infrared (near-IR) colors of z > 10 LBGs, representing potential contaminants in LBG candidate samples. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6σ SCUBA-2 detection at 850 μm around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4–6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations.

We report the discovery of a candidate galaxy with a photo-z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z phot = 11.8 − 0.2 + 0.3 (1σ uncertainty) with m F200W = 27.3 and ≳7σ detections in five filters. The source is not detected at λ < 1.4 μm in deep imaging from both Hubble Space Telescope (HST) and JWST and has faint ∼3σ detections in JWST F150W and HST F160W, which signal a Lyα break near the red edge of both filters, implying z ∼ 12. This object (Maisie’s Galaxy) exhibits F115W − F200W > 1.9 mag (2σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo-z probability distribution function favoring z > 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z > 11. Its colors are inconsistent with Galactic stars, and it is resolved (r h = 340 ± 14 pc). Maisie’s Galaxy has log M */M ⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr−1), with a blue rest-UV color (β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang.

Submillimeter/millimeter observations of dusty star-forming galaxies with the Atacama Large Millimeter/submillimeter Array (ALMA) have shown that dust continuum emission generally occurs in compact regions smaller than the stellar distribution. However, it remains to be understood how systematic these findings are. Studies often lack homogeneity in the sample selection, target discontinuous areas with inhomogeneous sensitivities, and suffer from modest $uv$ coverage coming from single array configurations. GOODS-ALMA is a 1.1mm galaxy survey over a continuous area of 72.42arcmin$^2$ at a homogeneous sensitivity. In this version 2.0, we present a new low resolution dataset and its combination with the previous high resolution dataset from the survey, improving the $uv$ coverage and sensitivity reaching an average of $��= 68.4��$Jy beam$^{-1}$. A total of 88 galaxies are detected in a blind search (compared to 35 in the high resolution dataset alone), 50% at $S/N_{peak} \geq 5$ and 50% at $3.5 \leq S/N_{peak} \leq 5$ aided by priors. Among them, 13 out of the 88 are optically dark or faint sources ($H$- or $K$-band dropouts). The sample dust continuum sizes at 1.1mm are generally compact, with a median effective radius of $R_{e} = 0"10 \pm 0"05$ (a physical size of $R_{e} = 0.73 \pm 0.29$kpc at the redshift of each source). Dust continuum sizes evolve with redshift and stellar mass resembling the trends of the stellar sizes measured at optical wavelengths, albeit a lower normalization compared to those of late-type galaxies. We conclude that for sources with flux densities $S_{1.1mm} > 1$mJy, compact dust continuum emission at 1.1mm prevails, and sizes as extended as typical star-forming stellar disks are rare. The $S_{1.1mm} < 1$mJy sources appear slightly more extended at 1.1mm, although they are still generally compact below the sizes of typical star-forming stellar disks., Accepted by A&A. 30 pages, 18 figures

Ly$α$ $λ$1216 (Ly$α$) emission extending over $\gtrsim\,\rm 10\,kiloparsec\,(kpc)$ around dusty, massive starbursts at $z\gtrsim3$ might represent a short-lived phase in the evolution of present-day, massive quiescent galaxies. To obtain empirical constraints on this emerging scenario, we present Ly$α$, CIV $λ$1550 (CIV), and HeII $λ$1640 (HeII) observations taken with the Multi Unit Spectroscopic Explorer towards J1000$+$0234: a galaxy pair at $z=4.5$ composed of a low-mass starburst (J1000$+$0234$-$South) neighboring a massive Submillimeter Galaxy (SMG; J1000$+$0234$-$North) that harbors a rotationally supported gas disk. Based on the spatial distribution and relative strength of Ly$α$, CIV, and HeII, we find that star formation in J1000+0234$-$South and an active galactic nucleus in J1000+0234$-$North are dominant factors in driving the observed 40 kiloparsec-scale Ly$α$ blob (LAB). We use the non-resonant HeII line to infer kinematic information of the LAB. We find marginal evidence for two spatially and spectrally separated HeII regions, which suggests that the two-peaked Ly$α$ profile is mainly a result of two overlapping and likely interacting HI clouds. We also report the serendipitous identification of three Ly$α$ emitters spanning over a redshift bin $Δz \leq 0.007$ (i.e., $\lesssim 380\,\rm km\,s^{-1}$) located at $\lesssim 140\,\rm kpc$ from J1000+0234. A galaxy overdensity analysis confirms that J1000+0234 lies near the center of a Megaparsec-scale galaxy overdensity at $z= 4.5$ that might evolve into a galaxy cluster at $z=0$. The properties of J1000+0234 and its large-scale environment strengthen the link between SMGs within LABs, tracing overdense regions, as the progenitors of local massive ellipticals in galaxy clusters., Accepted for publication in MNRAS

We analyse measurements of the evolving stellar mass (M0) at which the bending of the star-forming main sequence (MS) occurs over 01.4 (for which we propose a revision in agreement with latest simulations). We hence argue that the MS bending is primarily due to the lessening of cold-accretion causing a reduction in available cold gas in galaxies and supports predictions of gas feeding theory. In particular, the rapidly rising M0 with redshift at z>1 is confirming evidence for the cold-streams scenario. In this picture, a progressive fueling reduction rather than its sudden suppression in halos more massive than Mshock/Mstream produces a nearly constant star-formation rate in galaxies with stellar masses larger than M0, and not their quenching, for which other physical processes are thus required. Compared to the knee M* in the stellar mass function of galaxies, M0 is significantly lower at z2, suggesting that the imprint of gas deprivation on the distribution of galaxy masses happened at early times (z>1.5-2). The typical mass at which galaxies inside the MS become bulge-dominated evolves differently from M0, consistent with the idea that bulge-formation is a distinct process from the phasing-out of cold-accretion., A&A Letters, in press

Background and aims Clinical trials have shown that intensive low-density lipoprotein cholesterol (LDL-C) lowering improves cardiovascular outcomes among patients with atherosclerotic cardiovascular disease (ASCVD), but data are limited in real clinical practice, particularly for patients with ASCVD informing different territories. Methods FRENA was a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We compared the incidence of recurrent events in patients with sustained LDL-C levels As of December 2018, 1182 patients were eligible for this study. Among them, 172 (14.5%) had mean LDL-C levels = 70 mg/dl; the rate ratio was 0.61 (95% CI, 0.39-0.92), p = 0.019. On multivariable analysis, patients with LDL-C levels

Background This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. Methods PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with >= 2 comorbidities or aged >= 60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation Results Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. Conclusions Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. The PANCOVID clinical trial does not suggest a beneficial effect of tenofovir disoproxil fumarate/emtricitabine for mainly hospitalized patients at high risk of severe COVID-19. Our results are compatible with the beneficial effect of baricitinib already established by prior clinical trials.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation. Copyright © 2021 The Authors. Publicado por Elsevier Espana, S.L.U. All rights reserved.

The lipid theory of atherosclerosis dates back more than a century. Despite this, some authors have questioned the relevance of hypercholesterolaemia in its development. Multiple experimental, epidemiological, and clinical evidence underpins this association. Atherosclerotic cardiovascular disease remains as the major cause of mortality in the world. Recent genetic studies of Mendelian randomisation and randomised clinical trials aimed at LDL cholesterol reduction, are summarised in this article. They, unequivocally ratify the aetiological role of LDL cholesterol in the development of atherosclerosis. Thus, LDL cholesterol lowering is the cornerstone of lipid lowering therapy for the reduction of cardiovascular complications of atherosclerosis (c) 2021 Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Arteriosclerosis.

We analyse measurements of the evolving stellar mass (M0) at which the bending of the star-forming main sequence (MS) occurs over 01.4 (for which we propose a revision in agreement with latest simulations). We hence argue that the MS bending is primarily due to the lessening of cold-accretion causing a reduction in available cold gas in galaxies and supports predictions of gas feeding theory. In particular, the rapidly rising M0 with redshift at z>1 is confirming evidence for the cold-streams scenario. In this picture, a progressive fueling reduction rather than its sudden suppression in halos more massive than Mshock/Mstream produces a nearly constant star-formation rate in galaxies with stellar masses larger than M0, and not their quenching, for which other physical processes are thus required. Compared to the knee M* in the stellar mass function of galaxies, M0 is significantly lower at z2, suggesting that the imprint of gas deprivation on the distribution of galaxy masses happened at early times (z>1.5-2). The typical mass at which galaxies inside the MS become bulge-dominated evolves differently from M0, consistent with the idea that bulge-formation is a distinct process from the phasing-out of cold-accretion., Comment: A&A Letters, in press

Pooled data from randomized clinical trials on lipid-lowering therapy have provided valuable information and clinical insights. Although cardiovascular disease is a common cause of death, mortality data have rarely been prominent in key lipid trials. The 4S, LIPID and HPS trials were the first to demonstrate a reduction in overall mortality. Lower- versus higher-intensity statin trials and non-statin lipid-lowering trials with ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors proved that additional lipid lowering significantly reduces the occurrence of cardiovascular events. However, only the ODYSSEY OUTCOMES trial showed a reduction in all-cause mortality. The aim of the present narrative review was to contrast these results with those of other key lipid trials: those assessing statins compared with placebo, those evaluating intensive- versus moderate-intensity lipid-lowering therapy and, finally, those investigating non-statin lipid-lowering therapies.

The dust-to-stellar mass ratio ($M_{\rm dust}$/$M_{\rm \star}$) is a crucial yet poorly constrained quantity to understand the production mechanisms of dust, metals and stars in galaxy evolution. In this work we explore and interpret the nature of $M_{\rm dust}$/$M_{\rm \star}$ in 300 massive ($M_{\star}>10^{10}M_{\odot}$), dusty star-forming galaxies detected with ALMA up to $z\approx5$. We find that $M_{\rm dust}$/$M_{\rm \star}$ evolves with redshift, stellar mass, specific SFR and integrated dust size, differently for main sequence and starburst galaxies. In both galaxy populations $M_{\rm dust}$/$M_{\rm \star}$ rises until $z\sim2$ followed by a roughly flat trend towards higher redshifts. We show that the inverse relation between $M_{\rm dust}$/$M_{\rm \star}$ and $M_{\star}$ holds up to $z\approx5$ and can be interpreted as an evolutionary transition from early to late starburst phases. We demonstrate that $M_{\rm dust}$/$M_{\rm \star}$ in starbursts mirrors the increase in molecular gas fraction with redshift, and is enhanced in objects with the most compact dusty star-formation. The state-of-the-art cosmological simulation SIMBA broadly matches the evolution of $M_{\rm dust}$/$M_{\rm \star}$ in main sequence galaxies, but underestimates it in starbursts. The latter is found to be linked to lower gas-phase metallicities and longer dust growth timescales relative to data. Our data are well reproduced by analytical model that includes recipes for rapid metal enrichment, strongly suggesting that high $M_{\rm dust}$/$M_{\rm \star}$ is due to fast grain growth in metal enriched ISM. Our work highlights multifold benefits of using $M_{\rm dust}$/$M_{\rm \star}$ as a diagnostic tool for: (1) separating main sequence and starburst galaxies until $z\sim5$; (2) probing the evolutionary phases of dusty galaxies, and (3) refining the treatment of dust life cycle in simulations., Accepted for publication in A&A, main text 17 pages, 9 figures

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the population has affected the supply chains of these life-saving medical products. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. We also review different aspects of CAR T-cell therapy and our managerial experience of patient selection, resource prioritization and some practical aspects to consider for safe administration. Although hospitals have been forced to change their usual workflows to cope with the saturation of health services by hospitalized patients, we recommend centers to continue offering this potentially curative treatment for patients with relapsed/refractory hematologic malignancies. Consequently, we propose appropriate selection criteria, early intervention to attenuate neurotoxicity or cytokine release syndrome with tocilizumab and prophylactic/preventive strategies to prevent infection. These considerations may apply to other emerging adoptive cell treatments and the corresponding manufacturing processes.

The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. The bases of a diagnosis of FH are not entirely clear. The availability of genetic testing, including large genome-wide association analyses and whole genome studies, has shown that some patients with a clinical diagnosis of definite FH have no mutations in the genes associated with the disease. This fact does not exclude the very high cardiovascular risk of these patients, and an early and intensive lipid lowering therapy is recommended in all FH patients. Because an FH diagnosis is a cornerstone for decisions about therapies, a precise definition of FH is urgently required. This is an expert consensus document from the Spanish Atherosclerosis Society. We propose the following classification: familial hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia: patients with clinically definite FH and a functional mutation in one allele of the LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles; (3) polygenic familial hypercholesterolemia: patients with clinically definite FH but no mutations associated with FH are found (to be distinguished from non-familial, multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling clinically definite FH with associated hypertriglyceridemia.

Controlling cardiovascular risk factors (CV) is essential for patients with cardiovascular disease. The CV polypill contains aspirin 100 mg, atorvastatin 20 mg or 40 mg, and ramipril 2.5 mg, 5 mg or 10 mg in a fixed combination pill. The objective was to review the evidence on the secondary prevention of cardiovascular disease, to establish the eventual patient profiles suitabtes to consider the use of CV polypill with atorvastatin 40 mg in secondary CV prevention (P40PS), and to define the priority situations most adequate for the use of P40PS. A bibliographic review was carried out, which was complemented with the clinical opinion of 19 specialists. During hospitalization and discharge, P40PS is an option for patients admitted because of an atherothrombotic event, peripheral arterial disease, or other causes, and with the indication of the monocomponents. Its priority use is proposed in: prior intolerance to the highest dose of atorvastatin (80 mg), age >75 years, low weight, stage 3 of chronic renal failure, hypothyroidism, drug interactions and Asian origin. Outside the hospital setting, the P40PS is a therapeutic alternative in patients with a need for secondary CV prevention and with indication to receive the monocomponents. The priority situations to receive the P40PS are: to be taking the three components separately, to require polypharmacy, lack of adherence or understanding of the treatment, and lack of control of CV risk factors. This work is the first with proposals for the use of P40PS and can facilitate the treatment of patients with cardiovascular disease in secondary prevention. (C) 2018 Sociedad Espanola de Arteriosclerosis. Published by Elsevier Espana, S.L.U. All rights reserved.

Peripheral arterial disease (PAD) refers to the atherosclerotic involvement of non-coronary and extracranial arteries, including visceral arteries, the aorta and its branches and the arteries of the limbs. PAD usually refers exclusively to atherosclerosis of the limbs (in particular the lower limbs). Age, male sex, smoking and diabetes, as well as hypertension and dyslipidemia, are the most relevant risk factors for the development of PAD. PAD is frequently associated with coronary heart disease and stroke. PAD patients have increased risk of developing cardiovascular complications (coronary disease, stroke) and total and cardiovascular mortality, even after adjustment by conventional risk factors. Despite this PAD exhibit a worse control of risk factors. This opens up an important opportunity to optimize their control, which can result in an improvement of the prognosis of patients with PAD. Ischemic nephropathy includes a constellation of disorders that are frequently associated: hypertension, renal failure and renal artery stenosis (RAS). RAS risk factors are similar to those of PAD. Recent studies have shown that renal revascularization is not associated with improvement in blood pressure control, preservation of renal function or reduction of cardiovascular events in most patients. Therefore, revascularization should be reserved for selected cases on an individual basis. In all cases, a strict control of vascular risk factors should be attempted.

The accumulation of vascular smooth muscle cells (VSMC) in the intima is an early feature of atherosclerosis that results from a balance of migration from the media, proliferation, and eventual death (including programmed cell death) of VSMC. Several reports have described that HMG-CoA reductase inhibitors (statins) attenuate both the migration and proliferation of VSMC. However, the potential effect of statins on VSMC programmed cell death has received little attention.Human and rat VSMC were incubated with different concentration of statins in the presence of fetal bovine serum as a survival factor. The presence of apoptosis was evaluated by morphological criteria, flow cytometry and DNA electrophoresis.Lipophilic statins induced, in a dose-dependent manner the appearance of VSMC apoptosis. The effect of statins was fully reversed by mevalonate, farnesylpyrophosphate, and geranylgeranypyrophosphate, but not by cholesterol or other mevalonate metabolites, suggesting a role for isoprenoids in VSMC apoptosis. In addition, the induction of apoptosis by statins was associated with the inhibition of prenylation of Rho B.The present results suggest that protein prenylation inhibition by statins may be involved in statin-induced VSMC apoptosis. These data provide a new potential mechanism by which statins may modulate the evolution of atherosclerotic lesions.