Loose Ends for the Exomoon Candidate Host Kepler-1625b

The claim of an exomoon candidate in the Kepler-1625b system has generated substantial discussion regarding possible alternative explanations for the purported signal. In this work we examine in detail these possibilities. First, the effect of more flexible trend models is explored and we show that sufficiently flexible models are capable of attenuating the signal, although this is an expected byproduct of invoking such models. We also explore trend models using X and Y centroid positions and show that there is no data-driven impetus to adopt such models over temporal ones. We quantify the probability that the 500 ppm moon-like dip could be caused by a Neptune-sized transiting planet to be < 0.75%. We show that neither autocorrelation, Gaussian processes nor a Lomb-Scargle periodogram are able to recover a stellar rotation period, demonstrating that K1625 is a quiet star with periodic behavior < 200 ppm. Through injection and recovery tests, we find that the star does not exhibit a tendency to introduce false-positive dip-like features above that of pure Gaussian noise. Finally, we address a recent re-analysis by Kreidberg et al (2019) and show that the difference in conclusions is not from differing systematics models but rather the reduction itself. We show that their reduction exhibits i) slightly higher intra-orbit and post-fit residual scatter, ii) $\simeq$ 900 ppm larger flux offset at the visit change, iii) $\simeq$ 2 times larger Y-centroid variations, and iv) $\simeq$ 3.5 times stronger flux-centroid correlation coefficient than the original analysis. These points could be explained by larger systematics in their reduction, potentially impacting their conclusions.Comment: 21 pages, 4 tables, 11 figures. Accepted for publication in The Astronomical Journal, January 202

A Transiting Jupiter Analog

Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\pm0.02)$ $R_{\mathrm{Jup}}$, a low orbital eccentricity ($0.06_{-0.04}^{+0.10}$) and an equilibrium temperature of $(131\pm3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet ($1071.2323\pm0.0006$ d), paving the way for follow-up of this $K=11.8$ mag target.Comment: 14 pages, 10 figures. Accepted to ApJ. Posteriors available at https://github.com/CoolWorlds/Kepler-167-Posterior

Loose Ends for the Exomoon Candidate Host Kepler-1625b

The claim of an exomoon candidate in the Kepler-1625b system has generated substantial discussion regarding possible alternative explanations for the purported signal. In this work, we examine these possibilities in detail. First, the effect of more flexible trend models is explored, and we show that sufficiently flexible models are capable of attenuating the signal—although this is an expected byproduct of invoking such models. We also explore trend models using x- and y-centroid positions, and show that there is no data-driven impetus to adopt such models over temporal ones. We quantify the probability that the 500 ppm moon-like dip could be caused by a Neptune-sized transiting planet to be <0.75%. We show that neither autocorrelation, Gaussian processes, nor a Lomb–Scargle periodogram are able to recover a stellar rotation period, demonstrating that K1625 is a quiet star with periodic behavior <200 ppm. Through injection and recovery tests, we find that the star does not exhibit a tendency to introduce false-positive dip-like features above that of pure Gaussian noise. Finally, we address a recent reanalysis by Kreidberg et al. and show that the difference in conclusions is not from differing systematics models but rather the reduction itself. We show that their reduction exhibits, in comparison to the original analysis: (i) slightly higher intraorbit and post-fit residual scatter, (ii) ≃900 ppm larger flux offset at the visit change, (iii) ≃2 times larger y-centroid variations, and (iv) ≃3.5 times stronger flux-centroid correlation coefficient. These points could be explained by larger systematics in their reduction, potentially impacting their conclusions

A Transiting Jupiter analog

Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of $(0.91\pm 0.02)$ ${R}_{{\rm{J}}}$, a low orbital eccentricity (${0.06}_{-0.04}^{+0.10}$), and an equilibrium temperature of $(131\pm 3)$ K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target

Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy

Cytokine release syndrome (CRS) is a systemic inflammatory response associated with chimeric antigen receptor T-cell (CAR-T) therapies. In severe cases, CRS can be associated with coagulopathy and hypofibrinogenemia. We present our global multicenter experience with CRS-associated coagulopathy after tisagenlecleucel therapy in 137 patients with relapsed or refractory B-cell acute lymphoblastic leukemia from the ELIANA and ENSIGN trials. These trials included clinical guidelines for fibrinogen replacement during CRS-associated coagulopathy. Hypofibrinogenemia requiring replacement was observed only in patients with severe CRS. A higher percentage of patients who required replacement were <10 years old, compared with those who did not require replacement. Twenty-three patients received replacement for hypofibrinogenemia (<1.5 g/L); 9 of them developed marked hypofibrinogenemia (<1 g/L). Very low fibrinogen levels (<1 g/L) were documented in patients before maximal CRS (n = 1), during maximal CRS (n = 7), and at CRS improvement (n = 1). Although hypofibrinogenemia was the most clinically significant coagulopathy, some patients also developed prolonged prothrombin time and activated partial thromboplastin time and increased international normalized ratio, further increasing the risk of bleeding. Hypofibrinogenemia was effectively managed using fibrinogen concentrate or cryoprecipitate replacement; severe (grade 4) bleeding events were rare (n = 2). CRS-associated coagulopathy with hypofibrinogenemia is manageable according to empiric guidelines of fibrinogen replacement for CAR-T trials. Fibrinogen concentrate should be used when cryoprecipitate is not reliably available. Monitoring fibrinogen levels in patients with moderate or severe CRS is essential for avoiding potentially fatal bleeding events

Giant Outer Transiting Exoplanet Mass (GOT 'EM) Survey. IV. Long-term Doppler Spectroscopy for 11 Stars Thought to Host Cool Giant Exoplanets

Discovering and characterizing exoplanets at the outer edge of the transit method's sensitivity has proven challenging owing to geometric biases and the practical difficulties associated with acquiring long observational baselines. Nonetheless, a sample of giant exoplanets on orbits longer than 100 days has been identified by transit hunting missions. We present long-term Doppler spectroscopy for 11 such systems with observation baselines spanning a few years to a decade. We model these radial velocity observations jointly with transit photometry to provide initial characterizations of these objects and the systems in which they exist. Specifically, we make new precise mass measurements for four long-period giant exoplanets (Kepler-111 c, Kepler-553 c, Kepler-849 b, and PH-2 b), we place new upper limits on mass for four others (Kepler-421 b, KOI-1431.01, Kepler-1513 b, and Kepler-952 b), and we show that several "confirmed" planets are in fact not planetary at all. We present these findings to complement similar efforts focused on closer-in short-period giant planets, and with the hope of inspiring future dedicated studies of cool giant exoplanets.Comment: 35 pages, 24 figures, 11 tables. Accepted for publication in ApJ Supplemen

Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study

<p>Abstract</p> <p>Introduction</p> <p>There exists a small subset of children with autism spectrum disorders (ASD) characterized by fluctuating behavioral symptoms and cognitive skills following immune insults. Some of these children also exhibit specific polysaccharide antibody deficiency (SPAD), resulting in frequent infection caused by encapsulated organisms, and they often require supplemental intravenous immunoglobulin (IVIG) (ASD/SPAD). This study assessed whether these ASD/SPAD children have distinct immunological findings in comparison with ASD/non-SPAD or non-ASD/SPAD children.</p> <p>Case description</p> <p>We describe 8 ASD/SPAD children with worsening behavioral symptoms/cognitive skills that are triggered by immune insults. These ASD/SPAD children exhibited delayed type food allergy (5/8), treatment-resistant seizure disorders (4/8), and chronic gastrointestinal (GI) symptoms (5/8) at high frequencies. Control subjects included ASD children without SPAD (N = 39), normal controls (N = 37), and non-ASD children with SPAD (N = 12).</p> <p>Discussion and Evaluation</p> <p>We assessed their innate and adaptive immune responses, by measuring the production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in responses to agonists of toll like receptors (TLR), stimuli of innate immunity, and T cell stimulants. Transcription profiling of PB monocytes was also assessed. ASD/SPAD PBMCs produced less proinflammatory cytokines with agonists of TLR7/8 (IL-6, IL-23), TLR2/6 (IL-6), TLR4 (IL-12p40), and without stimuli (IL-1ß, IL-6, and TNF-α) than normal controls. In addition, cytokine production of ASD/SPAD PBMCs in response to T cell mitogens (IFN-γ, IL-17, and IL-12p40) and candida antigen (Ag) (IL-10, IL-12p40) were less than normal controls. ASD/non-SPAD PBMDs revealed similar results as normal controls, while non-ASD/SPAD PBMCs revealed lower production of IL-6, IL-10 and IL-23 with a TLR4 agonist. Only common features observed between ASD/SPAD and non-ASD/SPAD children is lower IL-10 production in the absence of stimuli. Transcription profiling of PB monocytes revealed over a 2-fold up (830 and 1250) and down (653 and 1235) regulation of genes in ASD/SPAD children, as compared to normal (N = 26) and ASD/non-SPAD (N = 29) controls, respectively. Enriched gene expression of TGFBR (p < 0.005), Notch (p < 0.01), and EGFR1 (p < 0.02) pathways was found in the ASD/SPAD monocytes as compared to ASD/non-SPAD controls.</p> <p>Conclusions</p> <p>The Immunological findings in the ASD/SPAD children who exhibit fluctuating behavioral symptoms and cognitive skills cannot be solely attributed to SPAD. Instead, these findings may be more specific for ASD/SPAD children with the above-described clinical characteristics, indicating a possible role of these immune abnormalities in their neuropsychiatric symptoms.</p

Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors.

Lympho-myeloid restricted early thymic progenitors (ETPs) are postulated to be the cell of origin for ETP leukemias, a therapy-resistant leukemia associated with frequent co-occurrence of EZH2 and RUNX1 inactivating mutations, and constitutively activating signaling pathway mutations. In a mouse model, we demonstrate that Ezh2 and Runx1 inactivation targeted to early lymphoid progenitors causes a marked expansion of pre-leukemic ETPs, showing transcriptional signatures characteristic of ETP leukemia. Addition of a RAS-signaling pathway mutation (Flt3-ITD) results in an aggressive leukemia co-expressing myeloid and lymphoid genes, which can be established and propagated in vivo by the expanded ETPs. Both mouse and human ETP leukemias show sensitivity to BET inhibition in vitro and in vivo, which reverses aberrant gene expression induced by Ezh2 inactivation