TESS unveils the phase curve of WASP-33b. Characterization of the planetary atmosphere and the pulsations from the star

We present the detection and characterization of the full-orbit phase curve and secondary eclipse of the ultra-hot Jupiter WASP-33b at optical wavelengths, along with the pulsation spectrum of the host star. We analyzed data collected by the Transiting Exoplanet Survey Satellite (TESS) in sector 18. WASP-33b belongs to a very short list of highly irradiated exoplanets that were discovered from the ground and were later visited by TESS. The host star of WASP-33b is of delta Scuti-type and shows nonradial pulsations in the millimagnitude regime, with periods comparable to the period of the primary transit. These completely deform the photometric light curve, which hinders our interpretations. By carrying out a detailed determination of the pulsation spectrum of the host star, we find 29 pulsation frequencies with a signal-to-noise ratio higher than 4. After cleaning the light curve from the stellar pulsations, we confidently report a secondary eclipse depth of 305.8 +/- 35.5 parts-per-million (ppm), along with an amplitude of the phase curve of 100.4 +/- 13.1 ppm and a corresponding westward offset between the region of maximum brightness and the substellar point of 28.7 +/- 7.1 degrees, making WASP-33b one of the few planets with such an offset found so far. Our derived Bond albedo, A_B = 0.369 +/- 0.050, and heat recirculation efficiency, epsilon = 0.189 +/- 0.014, confirm again that he behavior of WASP-33b is similar to that of other hot Jupiters, despite the high irradiation received from its host star. By connecting the amplitude of the phase curve to the primary transit and depths of the secondary eclipse, we determine that the day- and nightside brightness temperatures of WASP-33b are 3014 +/- 60 K and 1605 +/- 45 K, respectively. From the detection of photometric variations due to gravitational interactions, we estimate a planet mass of M_P = 2.81 +/- 0.53 M$_J.Comment: 19 pages, 15 figure

Loss of AND-34/BCAR3 Expression in Mice Results in Rupture of the Adult Lens

PURPOSE. AND-34/BCAR3 (Breast Cancer Anti-Estrogen Resistance 3) associates with the focal adhesion adaptor protein, p130CAS/BCAR1. Expression of AND-34 regulates epithelial cell growth pattern, motility, and growth factor dependence. We sought to establish the effects of the loss of AND-34 expression in a mammalian organism. METHODS. AND-34−/− mice were generated by homologous recombination. Histopathology, in situ hybridization, and western blotting were performed on murine tissues. RESULTS. Western analyses confirmed total loss of expression in AND-34−/− splenic lymphocytes. Mice lacking AND-34 are fertile and have normal longevity. While AND-34 is widely expressed in wild type mice, histologic analysis of multiple organs in AND-34−/− mice is unremarkable and analyses of lymphocyte development show no overt changes. A small percentage of AND-34−/− mice show distinctive small white eye lesions resulting from the migration of ruptured cortical lens tissue into the anterior chamber. Following initial vacuolization and liquefaction of the lens cortex first observed at postnatal day three, posterior lens rupture occurs in all AND-34−/− mice, beginning as early as three weeks and seen in all mice at three months. Western blot analysis and in situ hybridization confirmed the presence of AND-34 RNA and protein in lens epithelial cells, particularly at the lens equator. Prior data link AND-34 expression to the activation of Akt signaling. While Akt Ser 473 phosphorylation was readily detectable in AND-34+/+ lens epithelial cells, it was markedly reduced in the AND-34−/− lens epithelium. Basal levels of p130Cas phosphorylation were higher in AND-34+/+ than in AND-34−/− lens epithelium. CONCLUSIONS. These results demonstrate the loss of AND-34 dysregulates focal adhesion complex signaling in lens epithelial cells and suggest that AND-34-mediated signaling is required for maintenance of the structural integrity of the adult ocular lens.National Institutes of Health (RO1 CA114094); Logica Foundatio

Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer

Càncer de pròstata; Metàstasi neoplàsica; ImmunoteràpiaCáncer de próstata; Metástasis neoplásica; InmunoterapiaProstate cancer; Metastatic neoplasm; ImmunotherapyPURPOSE PROSTVAC, a viral vector–based immunotherapy, prolonged median overall survival (OS) by 8.5 months versus placebo in metastatic castration-resistant prostate cancer in a phase II study. This phase III study further investigated those findings. PATIENTS AND METHODS Patients were randomly assigned to PROSTVAC (Arm V; n = 432), PROSTVAC plus granulocyte-macrophage colony-stimulating factor (Arm VG; n = 432), or placebo (Arm P; n = 433), stratified by prostate-specific antigen (less than 50 ng/mL v 50 ng/mL or more) and lactate dehydrogenase (less than 200 v 200 U/L or more). Primary end point was OS. Secondary end points were patients alive without events (AWE)—namely, radiographic progression, pain progression, chemotherapy initiation, or death—at 6 months and safety. The study design was a superiority trial of PROSTVAC (Arm V or Arm VG) versus Arm P. Three interim analyses were planned. RESULTS At the third interim analysis, criteria for futility were met and the trial was stopped early. Neither active treatment had an effect on median OS (Arm V, 34.4 months; hazard ratio, 1.01; 95% CI, 0.84 to 1.20; P = .47; Arm VG, 33.2 months; hazard ratio, 1.02; 95% CI, 0.86 to 1.22; P = .59; Arm P, 34.3 months). Likewise, AWE at 6 months was similar (Arm V, 29.4%; odds ratio, 0.96; 95% CI, 0.71 to 1.29; Arm VG, 28.0%; odds ratio, 0.89; 95% CI, 0.66 to 1.20; placebo, 30.3%). Adverse events were similar for the treatment and placebo groups, with the most common being injection site reactions (62% to 72%) and fatigue (21% to 24%). Arrhythmias were the most common cardiac-related events (1.4% to 3.5%). There were no reports of either myocarditis or pericarditis. Serious treatment-related events occurred in less than 1% of all patients. CONCLUSION Whereas PROSTVAC was safe and well tolerated, it had no effect on OS or AWE in metastatic castration-resistant prostate cancer. Combination therapy is currently being explored in clinical trials.Supported by Bavarian Nordic, the National Institute for Health Research Biomedical Research Centre at the Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research. Funded in part by National Cancer Institute Cancer Center Support Grant No. P30-CA008748 and the Center for Cancer Research, National Cancer Institute.P30 CA008748/CA/NCI NIH HHS/United States DH_/Department of Health/United Kingdo

Diagnostic stewardship based on patient profiles: differential approaches in acute versus chronic infectious syndromes

Introduction: New diagnostics may be useful in clinical practice, especially in contexts of high prevalence of multidrug-resistant organisms (MDRO). However, misuse of diagnostic tools may lead to increased costs and worse patient outcome. Conventional and new techniques should be appropriately positioned in diagnostic algorithms to guide an appropriate use of antimicrobial therapy. Areas covered: A panel of experts identified 4 main areas in which the implementation of diagnostic stewardship is needed. Among chronic infections, bone and prosthetic joint infections and subacute-chronic intravascular infections and endocarditis represent common challenges for clinicians. Among acute infections, bloodstream infections and community-acquired pneumonia may be associated with high mortality and require appropriate diagnostic approach. Expert opinion: Diagnostic stewardship aims to improve the appropriate use of microbiological diagnostics to guide therapeutic decisions through appropriate and timely diagnostic testing. Here, diagnostic algorithms based on different patient profiles are proposed for chronic and acute clinical syndromes. In each clinical scenario, combining conventional and new diagnostic techniques is crucial to make a rapid and accurate diagnosis and to guide the selection of antimicrobial therapy. Barriers related to the implementation of new rapid diagnostic tools, such as high initial costs, may be overcome through their rational and structured use

Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?

BACKGROUND: The definition of 'long-COVID syndrome' (LCS) is still debated and describes the persistence of symptoms after viral clearance in hospitalized or non-hospitalized patients affected by coronavirus disease 2019 (COVID-19). AIM: In this study, we examined the prevalence and the risk factors of LCS in a cohort of patients with previous COVID-19 and followed for at least 6 months of follow-up. DESIGN: We conducted a prospective study including all hospitalized patients affected by COVID-19 at our center of Infectious Diseases (Vercelli, Italy) admitted between 10 March 2020 and 15 January 2021 for at least 6 months after discharge. Two follow-up visits were performed: after 1 and 6 months after hospital discharge. Clinical, laboratory and radiological data were recorded at each visit. RESULTS: A total of 449 patients were included in the analysis. The LCS was diagnosed in 322 subjects at Visit 1 (71.7%) and in 206 at Visit 2 (45.9); according to the post-COVID-19 functional status scale we observed 147 patients with values 2-3 and 175 with values >3 at Visit 1; at Visit 2, 133 subjects had the score between 2-3 and 73 > 3. In multivariate analysis, intensive care unit (ICU) admission (OR = 2.551; 95% CI = 1.998-6.819; P = 0.019), time of hospitalization (OR = 2.255; 95% CI = 1.018-6.992; P = 0.016) and treatment with remdesivir (OR = 0.641; 95% CI = 0.413-0.782; P < 0.001) were independent predictors of LCS. CONCLUSIONS: Treatment with remdesivir leads to a 35.9% reduction in LCS rate in follow-up. Severity of illness, need of ICU admission and length of hospital stay were factor associated with the persistence of PCS at 6 months of follow-up

Age determination of galaxy merger remnant stars using asteroseismology

The Milky Way was shaped by the mergers with several galaxies in the past. We search for remnant stars that were born in these foreign galaxies and assess their ages in an effort to put upper limits on the merger times and thereby better understand the evolutionary history of our Galaxy. Using 5D-phase space information from Gaia eDR3, radial velocities from Gaia DR2 and chemical information from apogee DR16, we kinematically and chemically select 21 red giant stars belonging to former dwarf galaxies that merged with the Milky Way. With added asteroseismology from Kepler and K2, we determine the ages of the 21 ex situ stars and 49 in situ stars with an average σage/age of ∼31 per cent. We find that all the ex situ stars are consistent with being older than 8 Gyr. While it is not possible to associate all the stars with a specific dwarf galaxy, we classify eight of them as Gaia-Enceladus/Sausage stars, which is one of the most massive mergers in our Galaxy's history. We determine their mean age to be 9.5 ± 1.3 Gyr consistent with a merger time of 8-10 Gyr ago. The rest of the stars are possibly associated with Kraken, Thamnos, Sequoia, or another extragalactic progenitor. The age determination of ex situ stars paves the way to more accurately pinning down when the merger events occurred and hence provide tight constraints useful for simulating how these events unfolded.Funding for the Stellar Astrophysics Centre was provided by The Danish National Research Foundation (grant agreement no. DNRF106). AH acknowledges support from a Spinoza prize from the Netherlands Research Council (NWO). HHK gratefully acknowledges financial support from a Fellowship at the Institute for Advanced Study. AS acknowledges support from the European Research Council Consolidator Grant funding scheme (project ASTEROCHRONOMETRY, G.A. n. 772293, http://www.asterochronometry.eu). JMDK gratefully acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through an Emmy Noether Research Group (grant number KR4801/1-1), as well as from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). CL acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 852839). JY acknowledges partial support from ERC Synergy Grant WHOLE SUN 810218

Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment

Purpose Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO (ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods In period one, men with chemotherapy-na¨ıve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression ($25$ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy

The first view of δ Scuti and γ Doradus stars with the TESS mission

We present the first asteroseismic results for δ Scuti and γ Doradus stars observed in Sectors 1 and 2 of the TESS mission. We utilize the 2-min cadence TESS data for a sample of 117 stars to classify their behaviour regarding variability and place them in the Hertzsprung-Russell diagram using Gaia DR2 data. Included within our sample are the eponymous members of two pulsator classes, γ Doradus and SX Phoenicis. Our sample of pulsating intermediate-mass stars observed by TESS also allows us to confront theoretical models of pulsation driving in the classical instability strip for the first time and show that mixing processes in the outer envelope play an important role. We derive an empirical estimate of 74 per cent for the relative amplitude suppression factor as a result of the redder TESS passband compared to the Kepler mission using a pulsating eclipsing binary system. Furthermore, our sample contains many high-frequency pulsators, allowing us to probe the frequency variability of hot young δ Scuti stars, which were lacking in the Kepler mission data set, and identify promising targets for future asteroseismic modelling. The TESS data also allow us to refine the stellar parameters of SX Phoenicis, which is believed to be a blue straggler.Fil: Antoci, Victoria. Stellar Astrophysics Centre; DinamarcaFil: Cunha, M. S.. Universidad de Porto; PortugalFil: Bowman, D. M.. Institute of Astronomy; BélgicaFil: Murphy, S. J.. Stellar Astrophysics Centre; Dinamarca. University of Sydney; AustraliaFil: Kurtz, D. W.. University of Central Lancashire; Reino UnidoFil: Bedding, T. R.. Stellar Astrophysics Centre; Dinamarca. University of Sydney; AustraliaFil: Borre, C. C.. Stellar Astrophysics Centre; DinamarcaFil: Christophe, S.. Universite de Paris I Pantheon - Sorbonne; Francia. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Daszynska Daszkiewicz, J.. Instytut Astronomiczny; PoloniaFil: Fox Machado, L.. Universidad Nacional Autónoma de México; MéxicoFil: García Hernández, A.. Universidad de Granada; EspañaFil: Ghasemi, Hamed. Institute For Advanced Studies In Basic Sciences; IránFil: Handberg, R.. Stellar Astrophysics Centre; DinamarcaFil: Hansen, Ted H.. Stellar Astrophysics Centre; DinamarcaFil: Hasanzadeh, A.. University Of Zanjan; IránFil: Houdek, G.. Stellar Astrophysics Centre; DinamarcaFil: Johnston, C.. Katholikie Universiteit Leuven; BélgicaFil: Justesen, A. B.. Stellar Astrophysics Centre; DinamarcaFil: Kahraman Alicavus, F.. Nicolaus Copernicus Astronomical Center Of The Polish Academy Of Sciences; PoloniaFil: Kotysz, K.. Instytut Astronomiczny, Uniwersytet Wrocławski; PoloniaFil: Latham, D.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Matthews, J. M.. University of British Columbia; CanadáFil: Mønster, J.. Stellar Astrophysics Centre; DinamarcaFil: Niemczura, E.. Uniwersytet Wrocławski; PoloniaFil: Paunzen, E.. Masaryk University; República ChecaFil: Sánchez Arias, Julieta Paz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Pigulski, A.. Uniwersytet Wrocławski; PoloniaFil: Pepper, J.. Lehigh University; Estados UnidosFil: Richey Yowell, T.. Lehigh University; Estados UnidosFil: Safari, H.. University of Zanjan; Irá