Brugada syndrome induced by BRAF and MEK inhibitors in a melanoma patient.

All-sky search in early O3 LIGO data for continuous gravitational-wave signals from unknown neutron stars in binary systems

Rapidly spinning neutron stars are promising sources of continuous gravitational waves. Detecting such a signal would allow probing of the physical properties of matter under extreme conditions. A significant fraction of the known pulsar population belongs to binary systems. Searching for unknown neutron stars in binary systems requires specialized algorithms to address unknown orbital frequency modulations. We present a search for continuous gravitational waves emitted by neutron stars in binary systems in early data from the third observing run of the Advanced LIGO and Advanced Virgo detectors using the semicoherent, GPU-accelerated, binaryskyhough pipeline. The search analyzes the most s…

Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients

ABSTRACT In the era of immunotherapies there is an urgent need to implement the use of circulating biomarkers in clinical practice to facilitate personalized therapy and to predict treatment response. We conducted a prospective study to evaluate the usefulness of circulating exosomal-PD-L1 in melanoma patients’ follow-up. We studied the dynamics of exosomal-PD-L1 from 100 melanoma patients by using an enzyme-linked immunosorbent assay. We found that PD-L1 was secreted through exosomes by melanoma cells. Exosomes carrying PD-L1 had immunosuppressive properties since they were as efficient as the cancer cell from which they derive at inhibiting T-cell activation. In plasma from melanoma patie…

Calibration of advanced Virgo and reconstruction of the gravitational wave signal h(t) during the observing run O2

In August 2017, Advanced Virgo joined Advanced LIGO for the end of the O2 run, leading to the first gravitational waves detections with the three-detector network. This paper describes the Advanced Virgo calibration and the gravitational wave strain h(t) reconstruction during O2. The methods are the same as the ones developed for the initial Virgo detector and have already been described in previous publications, this paper summarizes the differences and emphasis is put on estimating systematic uncertainties. Three versions of the h(t) signal have been computed for the Virgo O2 run, an online version and two post-run reprocessed versions with improved detector calibration and reconstruction…

Search for anisotropic gravitational-wave backgrounds using data from Advanced LIGO and Advanced Virgo's first three observing runs

We report results from searches for anisotropic stochastic gravitational-wave backgrounds using data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. For the first time, we include Virgo data in our analysis and run our search with a new efficient pipeline called {\tt PyStoch} on data folded over one sidereal day. We use gravitational-wave radiometry (broadband and narrow band) to produce sky maps of stochastic gravitational-wave backgrounds and to search for gravitational waves from point sources. A spherical harmonic decomposition method is employed to look for gravitational-wave emission from spatially-extended sources. Neither technique found eviden…

All-sky search for long-duration gravitational wave transients in the first Advanced LIGO observing run

Made available in DSpace on 2018-11-26T17:45:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-22 Australian Research Council Council of Scientific and Industrial Research of India Department of Science and Technology, India Science AMP; Engineering Research Board (SERB), India Ministry of Human Resource Development, India Spanish Agencia Estatal de Investigacion Vicepresidencia i Conselleria d'Innovacio, Recerca i Turisme Conselleria d'Educacio i Universitat del Govern de les Illes Balears Conselleria d'Educacio, Investigacio, Cultura i Esport de la Generalitat Valenciana National Science Centre of Poland Swiss National Science Foundation (SNSF) Russian Foundation for Basic Rese…

PD-L1 dans les exosomes circulants de patients atteints de mélanome : un nouveau biomarqueur ?

Le pronostic des patients atteints de melanome avance s’est considerablement ameliore depuis l’avenement des therapies ciblees et des immunotherapies. Cependant, tous les patients ne beneficient pas de ces traitements (tts) a cause de resistances primaires ou acquises. Il apparait donc indispensable de developper des biomarqueurs permettant de selectionner les patients potentiellement repondeurs aux tts, d’evaluer precocement l’efficacite de ces tts et diagnostiquer precocement la recidive de la maladie. Nous avons evalue l’interet du dosage de PD-L1 dans les exosomes circulants de patients atteints de melanome avance. Cent patients suivis entre novembre 2016 et janvier 2019 etaient inclus.…

MEK inhibitors combined with programmed cell death-1 blockade immunotherapy for metastatic uveal melanoma: is it warranted?

In the setting of metastatic uveal melanoma (mUM), prognosis is dismal and treatment options are limited. MEK inhibition using selumetinib has led to promising results with improved progression-free survival. While immune checkpoint inhibitors such as programmed cell death-1 (PD-1) blockade therapy (anti-PD-1) has shown discrete efficacy in mUM, combining MEK inhibitors (MEKi) to anti-PD-1 might be an option as such combinations have shown synergistic efficacy in metastatic cutaneous melanoma. We report here and discuss our experience in three patients who received this combination in the absence of suitable alternative treatment. The efficacy was difficult to assess due to early severe tox…

Visceral adiposity in patients with psoriatic arthritis and psoriasis alone and its relationship with metabolic and cardiovascular risk

Abstract Background Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO). Methods Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin…

Tests of General Relativity with GW170817

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in presence of matter. In this paper, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polari…

Erratum: “Searches for Gravitational Waves from Known Pulsars at Two Harmonics in 2015–2017 LIGO Data” (2019, ApJ, 879, 10)

Two analysis errors have been identified that affect the results for a handful of the high-value pulsars given in Table 1 of Abbott et al. (2019). One affects the Bayesian analysis for the five pulsars that glitched during the analysis period, and the other affects the 5n-vector analysis for J0711-6830. Updated results after correcting the errors are shown in Table 1, which now supersedes the results given for those pulsars in Table 1 of Abbott et al. (2019). Updated versions of figures can be seen in Figures 1-4. Bayesian analysis.-For the glitching pulsars, the signal phase evolution caused by the glitch was wrongly applied twice and was therefore not consistent with our expected model of…

GW190521: A Binary Black Hole Merger with a Total Mass of 150  M⊙

LIGO Scientific Collaboration and Virgo Collaboration: et al.

Deux observations de granulome annulaire sous anti-PD1

Resume Introduction Le granulome annulaire fait partie des reactions granulomateuses qui peuvent etre induites par des medicaments. L’immunotherapie par anti-PD1 est utilisee dans le traitement des melanomes et d’autres cancers solides. Nous rapportons deux cas de granulome annulaire survenus chez des patientes traitees par un anti-PD1, le pembrolizumab. Observations Deux femmes traitees par pembrolizumab toutes les 3 semaines pour un melanome metastatique ont developpe un granulome annulaire sous traitement. L’immunotherapie a ete maintenue dans les deux cas. Les lesions ont continue d’evoluer par poussees et remissions chez la premiere patiente, alors qu’une disparition complete etait con…

Cémiplimab et carcinomes épidermoïdes cutanés localement évolués ou métastatiques : premières données de vie réelle

Introduction Dans l’essai de phase 2 evaluant le cemiplimab (CEM) chez des patients (pts) ayant un carcinome epidermoide cutane (CEC) localement evolue ou metastatique, le taux de meilleure reponse (TMR) etait de 47 % et la survie globale (SG) a un an de 81 %. Une autorisation temporaire d’utilisation (ATU) nominative a permis a ces pts d’acceder au CEM hors protocole. Notre objectif etait d’analyser les donnees d’efficacite et de tolerance de cette ATU. Materiel et methodes Les 58 centres ayant inclus des pts entre le 08/18 et le 10/19 dans cette etude retrospective ont ete sollicites pour completer une fiche standardisee par pt. L’objectif principal etait le TMR, les objectifs secondaires…

Naturally Occurring Telomerase-Specific CD4 T-Cell Immunity in Melanoma.

CD4 T cells play a key role in anticancer immunity. In this study, we investigate the clinical relevance of circulating CD4 T helper type 1 (Th1) response against telomerase (anti-TERT Th1 response) in patients with melanoma. The spontaneous anti-TERT Th1 response was detected in 54.5% (85/156) of patients with melanoma before treatment. The prevalence of this systemic response was inversely related to Breslow thickness >1 mm and American Joint Committee on Cancer stage ≥II (P = 0.001 and 0.032, respectively). In contrast to patients treated with targeted therapies, the anti-TERT Th1 immunity was associated with an objective response after immune checkpoint inhibitors treatment. Hence, 86% …

Constraining the p -Mode– g -Mode Tidal Instability with GW170817

We analyze the impact of a proposed tidal instability coupling p modes and g modes within neutron stars on GW170817. This nonresonant instability transfers energy from the orbit of the binary to internal modes of the stars, accelerating the gravitational-wave driven inspiral. We model the impact of this instability on the phasing of the gravitational wave signal using three parameters per star: An overall amplitude, a saturation frequency, and a spectral index. Incorporating these additional parameters, we compute the Bayes factor (lnB!pgpg) comparing our p-g model to a standard one. We find that the observed signal is consistent with waveform models that neglect p-g effects, with lnB!pgpg=…

The advanced Virgo longitudinal control system for the O2 observing run

Following a successful period of data-taking between 2006 and 2011, the Virgo gravitational-wave detector was taken offline for a major upgrade. The changes made to the instrument significantly increased the complexity of the control systems and meant that an extended period of commissioning was required to reach a sensitivity appropriate for science data-taking. This commissioning period was completed in July of 2017 and the second-generation Advanced Virgo detector went on to join the Advanced LIGO detectors in the O2 science run in August of the same year. The upgraded detector was approximately twice as sensitive to binary neutron star mergers as the first-generation instrument. During …

Search for intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network

Gravitational wave astronomy has been firmly established with the detection of gravitational waves from the merger of ten stellar mass binary black holes and a neutron star binary. This paper reports on the all-sky search for gravitational waves from intermediate mass black hole binaries in the first and second observing runs of the Advanced LIGO and Virgo network. The search uses three independent algorithms: two based on matched filtering of the data with waveform templates of gravitational wave signals from compact binaries, and a third, model-independent algorithm that employs no signal model for the incoming signal. No intermediate mass black hole binary event was detected in this sear…

All-sky search for continuous gravitational waves from isolated neutron stars using Advanced LIGO O2 data

We present results of an all-sky search for continuous gravitational waves (CWs), which can be produced by fast-spinning neutron stars with an asymmetry around their rotation axis, using data from the second observing run of the Advanced LIGO detectors. We employ three different semi-coherent methods ($\textit{FrequencyHough}$, $\textit{SkyHough}$, and $\textit{Time-Domain $\mathcal{F}$-statistic}$) to search in a gravitational-wave frequency band from 20 to 1922 Hz and a first frequency derivative from $-1\times10^{-8}$ to $2\times10^{-9}$ Hz/s. None of these searches has found clear evidence for a CW signal, so we present upper limits on the gravitational-wave strain amplitude $h_0$ (the …

GW190412: Observation of a binary-black-hole coalescence with asymmetric masses

LIGO Scientific Collaboration and Virgo Collaboration: et al.

Gravitational-wave Constraints on the Equatorial Ellipticity of Millisecond Pulsars

We present a search for continuous gravitational waves from five radio pulsars, comprising three recycled pulsars (PSR J0437-4715, PSR J0711-6830, and PSR J0737-3039A) and two young pulsars: the Crab pulsar (J0534+2200) and the Vela pulsar (J0835-4510). We use data from the third observing run of Advanced LIGO and Virgo combined with data from their first and second observing runs. For the first time, we are able to match (for PSR J0437-4715) or surpass (for PSR J0711-6830) the indirect limits on gravitational-wave emission from recycled pulsars inferred from their observed spin-downs, and constrain their equatorial ellipticities to be less than 10-8. For each of the five pulsars, we perfor…

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3a

Abbott, R., et al. (LIGO and VIRGO Collaboration)

Cemiplimab for locally advanced and metastatic cutaneous squamous-cell carcinomas: Real-life experience from the French CAREPI study group

Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%

A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo

This paper presents the gravitational-wave measurement of the Hubble constant (H 0) using the detections from the first and second observing runs of the Advanced LIGO and Virgo detector network. The presence of the transient electromagnetic counterpart of the binary neutron star GW170817 led to the first standard-siren measurement of H 0. Here we additionally use binary black hole detections in conjunction with galaxy catalogs and report a joint measurement. Our updated measurement is H 0 = km s-1 Mpc-1 (68.3% of the highest density posterior interval with a flat-in-log prior) which is an improvement by a factor of 1.04 (about 4%) over the GW170817-only value of km s-1 Mpc-1. A significant …

All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run

We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well-modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant event…

Immunité spécifique anti-télomérase dans le mélanome

La reponse immunitaire lymphocytaire T CD4 Th1 joue un role important dans l’immunite anti tumorale et a ete etudiee dans de nombreux cancers. Nous avons evalue la reponse immunitaire T CD4 Th1 grâce a la reponse T CD4 Th1 anti-telomerase (anti-TERT) chez des patients atteints de melanome de tous stades AJCC. La reponse anti-TERT des lymphocytes de patients atteints de melanome etait evaluee par ELISpot IFN-γ et comparee aux donnees clinico-biologiques des patients. Au total, 171 patients atteints de melanome etaient inclus et 156 d’entre eux avaient une evaluation de la reponse anti-TERT disponible. Une reponse anti-TERT etait retrouvee chez 55 % des patients. La reponse anti-TERT etait mo…

Search for Subsolar-Mass Ultracompact Binaries in Advanced LIGO's First Observing Run

We present the first Advanced LIGO and Advanced Virgo search for ultracompact binary systems with component masses between 0.2 $M_\odot$ - 1.0 $M_\odot$ using data taken between September 12, 2015 and January 19, 2016. We find no viable gravitational wave candidates. Our null result constrains the coalescence rate of monochromatic (delta function) distributions of non-spinning (0.2 $M_\odot$, 0.2 $M_\odot$) ultracompact binaries to be less than $1.0 \times 10^6 \text{Gpc}^{-3} \text{yr}^{-1}$ and the coalescence rate of a similar distribution of (1.0 $M_\odot$, 1.0 $M_\odot$) ultracompact binaries to be less than $1.9 \times 10^4 \text{Gpc}^{-3} \text{yr}^{-1}$ (at 90 percent confidence). N…

Search for Gravitational-wave Signals Associated with Gamma-Ray Bursts during the Second Observing Run of Advanced LIGO and Advanced Virgo

We present the results of targeted searches for gravitational-wave transients associated with gamma-ray bursts during the second observing run of Advanced LIGO and Advanced Virgo, which took place from 2016 November to 2017 August. We have analyzed 98 gamma-ray bursts using an unmodeled search method that searches for generic transient gravitational waves and 42 with a modeled search method that targets compact-binary mergers as progenitors of short gamma-ray bursts. Both methods clearly detect the previously reported binary merger signal GW170817, with p-values of <9.38 10-6 (modeled) and 3.1 10-4 (unmodeled). We do not find any significant evidence for gravitational-wave signals associate…

Livedo: une présentation clinique rare de mycosis fongoïde avec vascularite

Introduction Le mycosis fongoide (MF), lymphome cutane T primitif le plus frequent, peut prendre des formes cliniques tres variees. Nous rapportons 3 cas d’une forme rare associant des plaques de MF a des lesions livedoides necrotiques correspondant a une vasculite cutanee (VC) associee. Materiel et methodes Cas 1: Un patient de 82 ans aux antecedents de leucemie lymphoide chronique B et de MF traite par dermocorticoides presentait un livedo racemosa du tronc, complique de necroses et ulcerations cutanees douloureuses. L’aspect histologique etait celui d’un infiltrat lymphoide dermique atypique, de phenotype T CD3(+), CD4(+), CD8(-) avec pilotropisme et epidermotropisme, associe en profonde…

A Fermi Gamma-Ray Burst Monitor Search for Electromagnetic Signals Coincident with Gravitational-wave Candidates in Advanced LIGO's First Observing Run

We present a search for prompt gamma-ray counterparts to compact binary coalescence gravitational wave (GW) candidates from Advanced LIGO's first observing run (O1). As demonstrated by the multimessenger observations of GW170817/GRB 170817A, electromagnetic and GW observations provide complementary information about the astrophysical source and, in the case of weaker candidates, may strengthen the case for an astrophysical origin. Here we investigate low-significance GW candidates from the O1 compact-binary coalescence searches using the Fermi Gamma-ray Burst Monitor (GBM), leveraging its all-sky and broad energy coverage. Candidates are ranked and compared to background to measure signific…

Suivi du taux de PD-L1 dans les exosomes pour évaluer la réponse tumorale dans le mélanome

Introduction Le pronostic des patients atteints de melanome avance s’est considerablement ameliore depuis l’avenement des therapies ciblees et des immunotherapies. Cependant, tous les patients ne beneficient pas de ces traitements a cause de resistances primaires ou acquises. Il apparait donc indispensable de developper des biomarqueurs permettant de selectionner les patients potentiellement repondeurs et permettant de surveiller l’efficacite des traitements. Nous avons evalue l’interet du dosage de PD-L1 dans les exosomes circulants de patients atteints de melanome avance. Materiel et methodes Cent patients suivis entre novembre 2016 et janvier 2019 etaient inclus. Les exosomes etaient iso…

GW170817: Measurements of Neutron Star Radii and Equation of State

On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation…

Search for GW signals associated with GRBs

We present the results of targeted searches for gravitational-wave transients associated with gamma-ray bursts during the second observing run of Advanced LIGO and Advanced Virgo, which took place from 2016 November to 2017 August. We have analyzed 98 gamma-ray bursts using an unmodeled search method that searches for generic transient gravitational waves and 42 with a modeled search method that targets compact-binary mergers as progenitors of short gamma-ray bursts. Both methods clearly detect the previously reported binary merger signal GW170817, with p-values of <9.38x10^-6^ (modeled) and 3.1x10^-4^ (unmodeled). We do not find any significant evidence for gravitational-wave signals assoc…