Aerosol characterisation in the subtropical eastern North Atlantic region using long-term AERONET measurements

A comprehensive characterisation of atmospheric aerosols in the subtropical eastern North Atlantic has been carried out using long-term ground-based Aerosol Robotic NETwork (AERONET) photometric observations over the period 2005–2020 from a unique network made up of four stations strategically located from sea level to 3555 m on the island of Tenerife. This site can be considered a sentinel for the passage of airmasses going to Europe from Africa, and therefore the aerosol characterisation performed here adds important information for analysing their evolution during their path toward Northern Europe. Two of these stations (Santa Cruz de Tenerife – SCO – at sea level and La Laguna – LLO – at 580 m a.s.l.) are located within the marine atmospheric boundary layer (MABL), and the other two (Izaña – IZO – at 2373 m a.s.l. and Teide Peak – TPO – at 3555 m a.s.l.) are high mountain stations within the free troposphere (FT). Monthly climatology of the aerosol optical depth (AOD), Ångström exponent (AE), aerosol concentration, size distribution and aerosol optical properties has been obtained for the MABL and FT. Measurements that are quite consistent across the four sites have been used to categorise the main atmospheric scenarios, and these measurements confirm an alternation between predominant background conditions and predominant dust-loaded Saharan air mass conditions caused by seasonal dust transport over the subtropical North Atlantic. Background conditions prevail in the MABL and FT for most of the year, while dust-laden conditions dominate in July and August.The authors also acknowledge the support from ACTRIS, Ministerio de Ciencia e Innovación, Spain, through the projects SYNERA (PID2020-118793GA-I00) and ePOLAAR (RTI2018-097864-BI00) and from Junta de Castilla y León (grant no. VA227P20)

Detection of X-ray elongated emission from a ultraluminous X-ray source in the interacting pair of galaxies NGC 5953/5954

We present radio through X-ray results of a bright (10^{40} erg/s in the 0.5 to 8.0 keV band) ultraluminous X-ray source (ULX), CXOU J153434.9+151149, in the starburst, interacting pair of galaxies NGC 5953/5954. Chandra image of this ULX shows that it is elongated. From HST/WFPC2/F606W data we have detected a counterpart of the ULX system with M_{F606W} ~-7.1 \pm 0.7 mag. This optical counterpart may be either an O-type supergiant star or a young star cluster. From our Fabry-Perot interferometric observations, we have detected Halpha and [NII](6584 A) diffuse emission, with velocity gradients up to 60 km/s at the astrometric corrected Chandra position of the ULX. Different scenarios have been invoked as to explain the possible nature of CXOU J153434.9+151149. Based on the observed X-ray morphology of the ULX, we determine that the inclination angle to the elongated emission will be ~53 deg. Beaming with this geometry from a stellar-mass black hole system will be inadequate to explain the observed X-ray luminosity of this ULX. Finally, we suggest that mild-beaming from a binary black hole with mass more than 50 solar masses, associated with a young star cluster, is the most favorable scenario that describes the multiwavelength properties of this ULX. Future observations are highly essential to determine the nature of this rare object.Comment: 34 pages (referee format), 5 figures, accepted for publication in A

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Comparison of settlements by geodetic methods and numerical modeling. Test case: fuel storage tank

This research project addresses the necessity to update the admissible values of defor-mations, set by the rules for the design of foundations, based on the comparative analysis of settlements determined by direct (geodetic) methods on conditions of field, with the vertical displacements obtained by the ¨deterministic¨ numerical modeling by the finite element method (FEM). In order to, a shallow foundation of a tank for the storage of fuel was selected as a case study. In addition, the geodetic measurements made during the water load test were taken as a reference pattern, using the high precision geometric leveling and the soft-ware SIGMA / W module of the GeoStudio 2012 was used to perform the calculation of verti-cal displacements. The comparison was carried out with respect to the absolute maximum settlement, for different time intervals and load steps; observing an acceptable correlation between the settlements measured and those calculated by numerical modeling, evidencing the feasibility of using this software for the forecast of settlements. This investigation pro-vides valuable information on the real deformations, for the control of works during the con-struction and operation processes. The results allow the improvement of the methods of cal-culation and design of foundations based on the limit state of deformation, as well as alert-ing about the operational safety of this type of work in the Cuban industry. The use of the geodesic method allows to check the software parameters and to adjust the limit values of the displacements fixed in the current regulations

A heat-shocked melanoma cell lysate vaccine enhances tumor infiltration by prototypic effector T cells inhibiting tumor growth

Background Immune checkpoint blocker (ICB) therapy has shown survival benefits for some patients with cancer. Nevertheless, many individuals remain refractory or acquire resistance to treatment, motivating the exploration of complementary immunotherapies. Accordingly, cancer vaccines offer an attractive alternative. Optimal delivery of multiple tumor-associated antigens combined with potent adjuvants seems to be crucial for vaccine effectiveness.Methods Here, a prototype for a generic melanoma vaccine, named TRIMELVax, was tested using B16F10 mouse melanoma model. This vaccine is made of heat shock-treated tumor cell lysates combined with the Concholepas concholepas hemocyanin as adjuvant.Results While B16F10 lysate provides appropriate melanoma-associated antigens, both a generic human melanoma cell lysate and hemocyanin adjuvant contributes with danger signals promoting conventional dendritic type 1 cells (cDC1), activation, phagocytosis and effective antigen cross-presentation. TRIMELVax inhibited tumor growth and increased mice survival, inducing cellular and humoral immune responses. Furthermore, this vaccine generated an increased frequency of intratumor cDC1s but not conventional type 2 dendritic cells (cDC2s). Augmented infiltration of CD3+, CD4+ and CD8+ T cells was also observed, compared with anti-programmed cell death protein 1 (PD-1) monotherapy, while TRIMELVax/anti-PD-1 combination generated higher tumor infiltration of CD4+ T cells. Moreover, TRIMELVax promoted an augmented proportion of PD-1lo CD8+ T cells in tumors, a phenotype associated with prototypic effector cells required for tumor growth control, preventing dysfunctional T-cell accumulation.Conclusions The therapeutic vaccine TRIMELVax efficiently controls the weakly immunogenic and aggressive B16F10 melanoma tumor growth, prolonging tumor-bearing mice survival even in the absence of ICB. The strong immunogenicity shown by TRIMELVax encourages clinical studies in patients with melanoma

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. PATIENTS AND METHODS: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of Cb (AUC 6) + D (75mg/m2) given every 21 days × 6 cycles. Pathological complete response (pCR: no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35mm, 52% Lymph Node positive and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0+1 rates were 55% and 68%, respectively. pCR in patients with BRCA associated and wild-type TNBC were 59% and 56%, respectively (p=0.83). On multivariable analysis stage III disease was the only factor associated with a lower likelihood of achieving a pCR. 21% and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSION: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA associated and wildtype TNBC. These results are comparable to pCR achieved with addition of Cb to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies