Recurrence risk of occult micrometastases and isolated tumor cells in early stage endometrial cancer: A case control study

Objectives: To determine whether previously undetected occult micrometastasis (MM) or isolated tumor cells (ITC) is associated with increased recurrence odds in stage I-II endometrioid adenocarcinoma. Methods: Women with recurrent stage I/II EC who had complete pelvic and para-aortic were identified as the outcome of interest. A case-control study was designed with the exposure defined as occult MM/ITC not seen on original nodal pathology. Controls were found by frequency-matching in a 1:2 case control ratio. Original nodal slides were re-reviewed, stained and tested with immunohistochemical to detect occult MM/ITC and the odds of associated recurrence was calculated. Results: Of 153 included, 50 with and 103 without recurrence, there was no difference in age (p = 0.46), race (p = 0.24), stage (p = 0.75), FIGO grade (p = 0.64), lymphovascular space invasion (LVSI); p = 1.00, or GOG 99 high-intermediate risk (HIR) criteria (p = 0.35). A total of 18 ITC (11.8%) and 3 MM (2.0%) not previously identified were found in 19 patients. Finding occult MM/ITC was not associated with more lymph nodes (LN) removed (p = 0.67) or tumor grade (p = 0.48) but was significantly associated with stage (p \u3c 0.01). LVSI (p = 0.09) and meeting high-intermediate risk criteria (p = 0.09), were closely associated but not statistically significant. Isolated ITC were not associated with increased odds for recurrence (OR 0.71, CL: 0.20 - 2.22, p = 0.57), recurrence free survival (RFS) (p = 0.85) or overall survival (OS) (p = 0.92). Conclusions: In early-stage EC, identification of occult MM or ITC is uncommon and associated with stage. The presence of ITC was not associated with increased odds of recurrence. Adjusting stage or treatment may avoided based on ITC alone. Isolated MM were rare in our population, and further investigation is warranted

On the Evolution of the Star Formation Rate Function of Massive Galaxies. Constraints at 0.4<z<1.8 from the GOODS-MUSIC Catalogue

[abridged] We study the evolution of the Star Formation Rate Function (SFRF) of massive galaxies over the 0.4<z<1.8 redshift range and its implications for our understanding of the physical processes responsible for galaxy evolution. We use multiwavelength observations included in the GOODS-MUSIC catalogue, which provides a suitable coverage of the spectral region from 0.3 to 24 micron and either spectroscopic or photometric redshifts for each object. Individual SFRs have been obtained by combining UV and 24 micron observations, when the latter were available. For all other sources an "SED fitting" SFR estimate has been considered. We then define a stellar mass limited sample, complete in the Mstar>1.e10 Msun range and determine the SFRF using the 1/Vmax algorithm. We define simulated galaxy catalogues based on three different semi-analytical models of galaxy formation and evolution. We show that the theoretical SFRFs are well described by a double power law functional form and its redshift evolution is approximated with high accuracy by a pure evolution of the typical SFR. We find good agreement between model predictions and the high-SFR end of the SFRF, when the observational errors on the SFR are taken into account. However, the observational SFRF is characterised by a double peaked structure, which is absent in its theoretical counterparts. At z>1.0 the observed SFRF shows a relevant density evolution, which is not reproduced by SAMs, due to the well known overprediction of intermediate mass galaxies at z~2. The agreement at the low-SFR end is poor: all models overpredict the space density of SFR~1 Msun/yr and no model reproduces the double peaked shape of the observational SFRF. If confirmed by deeper IR observations, this discrepancy will provide a key constraint on theoretical modelling of star formation and stellar feedback.Comment: 12 pages, 4 figures and 3 table. Accepted for publication by MNRAS - updated reference

Abordando la exposición a las emisiones del tabaco y de los cigarrillos electrónicos: protocolo del proyecto TackSHS

Objective The TackSHS project aims to comprehensively elucidate the impact that exposure to second-hand smoke (SHS) from cigarettes and second-hand aerosols (SHA) from electronic cigarettes have on the respiratory health of the European population according to socioeconomic characteristics and other determinants. Method The TackSHS project involves a series of coordinated studies carried out by 11 academic and public health organisations from six European countries. The project will investigate: a) the determinants of SHS and SHA exposure assessed at the individual level (surveys on representative general population samples) and in common environments (environmental sampling in specific settings); b) the overall disease burden, mortality and morbidity attributable to such exposure; and c) its economic impact in terms of direct health care costs. The project will also examine specific acute respiratory health changes in healthy individuals and patients with respiratory diseases exposed to SHS and SHA. In addition, the project will examine the effectiveness of a novel intervention to reduce SHS exposure in households where smoking is permitted. All these studies are inter-related and involve collaborative coordination among the participant organisations. Conclusion The comprehensive, integrated approach of the TackSHS project will enable a significant step forward from the current status quo in the understanding of the impact of SHS and SHA exposure on health and provide the basis for health policy recommendations to help European countries to further reduce the harm caused by SHS and SHA exposure.Additional co-authors: Montse Ballbè, Beladenta Amalia, Olena Tigova, Xavier Continente, Teresa Arechávala, Elisabet Henderson, Alessandra Lugo, Xiaoqiu Liu, Cristina Bosetti, Enrico Davoli, Paolo Colombo, Sheila Keogan, Shashsa Li, Elizabeth Breslin, Hannah Byrne, Anna Tzortzi, Constantine Vardavas, Vergina Konstantina Vyzikidou, Stephanie Teloniatis, Gerasimos Bakelas, George Mattiampa, Roberto Boffi, Cinzia De Marco, Alessandro Borgini, Chiara Veronese, Martina Bertoldi, Andrea Tittarelli, Giulia Carreras, Barbara Cortini, Simona Verdi, Alessio Lachi, Elisabetta Chellini, Marta Trapero-Bertran, Daniel Celdrán Guerrero, Dominick Nguyen, Polina Starchenko, Julio Ancochea, Tamara Alonso, María Teresa Pastor, Marta Erro, Ana Roca, Patricia Pére

Evaluating metagenomics and targeted approaches for diagnosis and surveillance of viruses

: Background : Metagenomics is a powerful approach for the detection of unknown and novel pathogens. Workflows based on Illumina short-read sequencing are becoming established in diagnostic laboratories. However, high sequencing depth requirements, long turnaround times, and limited sensitivity hinder broader adoption. We investigated whether we could overcome these limitations using protocols based on untargeted sequencing with Oxford Nanopore Technologies (ONT), which offers real-time data acquisition and analysis, or a targeted panel approach, which allows the selective sequencing of known pathogens and could improve sensitivity. Methods: We evaluated detection of viruses with readily available untargeted metagenomic workflows using Illumina and ONT, and an Illumina-based enrichment approach using the Twist Bioscience Comprehensive Viral Research Panel (CVRP), which targets 3153 viruses. We tested samples consisting of a dilution series of a six-virus mock community in a human DNA/RNA background, designed to resemble clinical specimens with low microbial abundance and high host content. Protocols were designed to retain the host transcriptome, since this could help confirm the absence of infectious agents. We further compared the performance of commonly used taxonomic classifiers. Results: Capture with the Twist CVRP increased sensitivity by at least 10–100-fold over untargeted sequencing, making it suitable for the detection of low viral loads (60 genome copies per ml (gc/ml)), but additional methods may be needed in a diagnostic setting to detect untargeted organisms. While untargeted ONT had good sensitivity at high viral loads (60,000 gc/ml), at lower viral loads (600–6000 gc/ml), longer and more costly sequencing runs would be required to achieve sensitivities comparable to the untargeted Illumina protocol. Untargeted ONT provided better specificity than untargeted Illumina sequencing. However, the application of robust thresholds standardized results between taxonomic classifiers. Host gene expression analysis is optimal with untargeted Illumina sequencing but possible with both the CVRP and ONT. Conclusions: Metagenomics has the potential to become standard-of-care in diagnostics and is a powerful tool for the discovery of emerging pathogens. Untargeted Illumina and ONT metagenomics and capture with the Twist CVRP have different advantages with respect to sensitivity, specificity, turnaround time and cost, and the optimal method will depend on the clinical context

Exposure to secondhand aerosol from electronic cigarettes at homes: A real-life study in four European countries

Electronic cigarette (e-cigarette) use emits potentially hazardous compounds and deteriorates indoor air quality. Home is a place where e-cigarettes may frequently be used amid its increasing prohibition in public places. This study assessed the real-life scenario of bystanders' exposure to secondhand e-cigarette aerosol (SHA) at home. A one-week observational study was conducted within the TackSHS project in four countries (Greece, Italy, Spain, and the United Kingdom) in 2019 including: 1) homes of e-cigarette users living together with a non-user/non-smoker; and 2) control homes with no smokers nor e-cigarette users. Indoor airborne nicotine, PM2.5, and PM1.0 concentrations were measured as environmental markers of SHA. Biomarkers, including nicotine and its metabolites, tobacco -specific nitrosamines, propanediol, glycerol, and metals were measured in participants' saliva and urine samples. E-cigarette use characteristics, such as e-cigarette refill liquid's nicotine concentration, e-cigarette type, place of e-cigarette use at home, and frequency of ventilation, were also collected. A total of 29 e-cigarette users' homes and 21 control homes were included. The results showed that the seven-day concentrations of airborne nicotine were quantifiable in 21 (72.4 %) out of 29 e-cigarette users' homes; overall, they were quite low (geometric mean: 0.01 mu g/m3; 95 % CI: 0.01-0.02 mu g/m(3)) and were all below the limit of quantification in control homes. Seven-day concentrations of PM2.5 and PM1.0 in e-cigarette and control homes were similar. Airborne nicotine and PM concentrations did not differ according to different e-cigarette use characteristics. Non-users residing with e-cigarette users had low but significantly higher levels of cotinine, 3 '-OH-cotinine and 1,2-propanediol in saliva, and cobalt in urine than non-users living in control homes. In conclusion, e-cigarette use at home created bystanders' exposure to SHA regardless of the e-cigarette use characteristics. Further studies are warranted to assess the implications of SHA exposure for smoke-free policy

The Evolution of the Galaxy Rest-Frame Ultraviolet Luminosity Function Over the First Two Billion Years

We present a robust measurement and analysis of the rest-frame ultraviolet (UV) luminosity function at z=4-8. We use deep Hubble Space Telescope imaging over the CANDELS/GOODS fields, the Hubble Ultra Deep Field and the Year 1 Hubble Frontier Field deep parallel observations. These surveys provides an effective volume of 0.6-1.2 x 10^6 Mpc^3 over this epoch, allowing us to perform a robust search for faint (M_UV=-18) and bright (M_UV < -21) galaxies. We select candidate galaxies using a well-tested photometric redshift technique with careful screening of contaminants, finding a sample of 7446 galaxies at 3.51000 galaxies at z~6-8. We measure the luminosity function using a Markov Chain Monte Carlo analysis to measure robust uncertainties. At the faint end our results agree with previous studies, yet we find a higher abundance of UV-bright galaxies at z>6, with M* ~ -21 at z>5, different than that inferred based on previous trends at lower redshift. At z=8, a single power-law provides an equally good fit to the UV luminosity function, while at z=6 and 7, an exponential cutoff at the bright-end is moderately preferred. We compare to semi-analytical models, and find that the lack of evolution in M* is consistent with models where the impact of dust attenuation on the bright-end of the luminosity function decreases at higher redshift. We measure the evolution of the cosmic star-formation rate density, correcting for dust attenuation, and find that it declines as (1+z)^(-4.3 +/- 0.5) at z>4, consistent with observations at z>9. Our observations are consistent with a reionization history that starts at z>10, completes at z>6, and reaches a midpoint (x_HII = 0.5) at 6.7<z<9.4. Finally, our observations predict that the abundance of bright z=9 galaxies is likely higher than previous constraints, though consistent with recent estimates of bright z~10 galaxies. [abridged]Comment: Re-submitted to the Astrophysical Journal after first referee's report. 34 pages, 21 figures, 7 tables. The source file includes a machine readable table of our full galaxy sampl

Exposure to secondhand and thirdhand smoke in private vehicles: Measurements in air and dust samples

Background: This study aimed to estimate airborne nicotine concentrations and nicotine, cotinine, and tobaccospecific nitrosamines (TSNAs) in settled dust from private cars in Spain and the UK. Methods: We measured vapor-phase nicotine concentrations in a convenience sample of 45 private cars from Spain (N = 30) and the UK (N = 15) in 2017-2018. We recruited non-smoking drivers (n = 20), smoking drivers who do not smoke inside the car (n = 15), and smoking drivers who smoke inside (n = 10). Nicotine, cotinine, and three TSNAs (NNK, NNN, NNA) were also measured in settled dust in a random subsample (n = 20). We computed medians and interquartile ranges (IQR) of secondhand smoke (SHS) and thirdhand smoke (THS) compounds according to the drivers' profile. Results: 24-h samples yielded median airborne nicotine concentrations below the limit of quantification (LOQ) (IQR

CEERS Key Paper. V. Galaxies at 4 &lt; z &lt; 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

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children