Hydroxychloroquine and short-course radiotherapy in elderly patients with newly diagnosed high-grade glioma: a randomized phase II trial

Background: Effective treatment for patients at least 70 years with newly diagnosed glioblastoma remains challenging and alternatives to conventional cytotoxics are appealing. Autophagy inhibition has shown promising efficacy and safety in small studies of glioblastoma and other cancers. Methods: We conducted a randomized phase II trial to compare radiotherapy with or without hydroxychloroquine (2:1 allocation). Patients aged at least 70 years with newly diagnosed high-grade glioma deemed suitable for short-course radiotherapy with an ECOG performance status of 0–1 were included. Radiotherapy treatment consisted of 30 Gy, delivered as 6 fractions given over 2 weeks (5 Gy per fraction). Hydroxychloroquine was given as 200 mg orally b.d. from 7 days prior to radiotherapy until disease progression. The primary endpoint was 1-year overall survival (OS). Secondary endpoints included progression-free survival (PFS), quality of life, and toxicity. Results: Fifty-four patients with a median age of 75 were randomized between May 2013 and October 2016. The trial was stopped early in 2016. One-year OS was 20.3% (95% confidence interval [CI] 8.2–36.0) hydroxychloroquine group, and 41.2% (95% CI 18.6–62.6) radiotherapy alone, with a median survival of 7.9 and 11.5 months, respectively. The corresponding 6-month PFS was 35.3% (95% CI 19.3–51.7) and 29.4% (95% CI 10.7–51.1). The outcome in the control arm was better than expected and the excess of deaths in the hydroxychloroquine group appeared unrelated to cancer. There were more grade 3–5 events in the hydroxychloroquine group (60.0%) versus radiotherapy alone (38.9%) without any clear common causation. Conclusions: Hydroxychloroquine with short-course radiotherapy did not improve survival compared to radiotherapy alone in elderly patients with glioblastoma

CONCERTO: High-fidelity simulation of millimeter line emissions of galaxies and [CII] intensity mapping

The intensity mapping of the [CII] 158-μm line redshifted to the submillimeter window is a promising probe of the za>4 star formation and its spatial distribution into large-scale structures. To prepare the first-generation experiments (e.g., CONCERTO), we need realistic simulations of the submillimeter extragalactic sky in spectroscopy. We present a new version of the simulated infrared dusty extragalactic sky (SIDES) model including the main submillimeter lines around 1 mm (CO, [CII], [CI]). This approach successfully reproduces the observed line luminosity functions. We then use our simulation to generate CONCERTO-like cubes (125-305 GHz) and forecast the power spectra of the fluctuations caused by the various astrophysical components at those frequencies. Depending on our assumptions on the relation between the star formation rate and [CII] luminosity, and the star formation history, our predictions of the za∼6 [CII] power spectrum vary by two orders of magnitude. This highlights how uncertain the predictions are and how important future measurements will be to improve our understanding of this early epoch. SIDES can reproduce the CO shot noise recently measured at a4;100 GHz by the millimeter-wavelength intensity mapping experiment (mmIME). Finally, we compare the contribution of the different astrophysical components at various redshifts to the power spectra. The continuum is by far the brightest, by a factor of three to 100, depending on the frequency. At 300 GHz, the CO foreground power spectrum is higher than the [CII] one for our base scenario. At lower frequencies, the contrast between [CII] and extragalactic foregrounds is even worse. Masking the known galaxies from deep surveys should allow us to reduce the foregrounds to 20% of the [CII] power spectrum up to z∼ 6.5. However, this masking method will not be sufficient at higher redshifts. The code and the products of our simulation are released publicly, and can be used for both intensity mapping experiments and submillimeter continuum and line surveys

CONCERTO: Extracting the power spectrum of the [C II ] emission line

CONCERTO is the first experiment to perform a [CII] line intensity mapping survey to target $z>5.2$. Measuring the [CII] power spectrum allows us to study the role of dusty star-forming galaxies in the star formation history during the Reionization and post-Reionization. The main obstacle to this measurement is the contamination by bright foregrounds. We evaluate our ability to retrieve the [CII] signal in mock observations using the Simulated Infrared Dusty Extragalactic Sky. We compared two methods for dealing with the dust continuum emission from galaxies: the standard PCA and the arPLS method. For line interlopers, the strategy relies on masking low-redshift galaxies using external catalogues. As we do not have observations of CO or classical CO proxies ,we relied on the COSMOS stellar mass catalogue. To measure the power spectrum of masked data, we adapted the P of K EstimatoR and discuss its use on LIM data. The arPLS method achieves a reduction of the continuum background to a sub-dominant level of the [CII] at z=7 by a factor of>70. When using PCA, this factor is only 0.7. The masking lowers the power amplitude of line contamination down to $2 \times 10^2 Jy^2/sr$ This residual level is dominated by faint undetected sources. For our [CII] model, this results in a detection at z = 5.2 with a power ratio [CII]/(residual interlopers) = $62 \pm 32$ for a 22 % area survey loss. However, at z = 7, [C II ] / (residual interlopers)$=2.0 \pm 1.4$. Thanks to the large area covered by SIDES-Uchuu, we show that the power amplitude of line residuals varies by 12-15% for z=5.2-7. We present an end-to-end simulation of the extragalactic foreground removal that we ran to detect the [CII] at high redshift via its power spectrum. We show that dust continuum emission are not a limiting foreground for [CII] LIM. Residual CO and [CI] limits our ability to measure the [CII] power spectrum at z>7.Comment: 15 pages, 12 figures, to be published in Astronomy & Astrophysic

CONCERTO: Simulating the CO, [CII], and [CI] line emission of galaxies in a 117 deg2 field and the impact of field-to-field variance

In the submillimeter regime, spectral line scans and line intensity mapping (LIM) are new promising probes for the cold gas content and star formation rate of galaxies across cosmic time. However, both of these two measurements suffer from field-to-field variance. We study the effect of field-to-field variance on the predicted CO and [CII] power spectra from future LIM experiments such as CONCERTO, as well as on the line luminosity functions (LFs) and the cosmic molecular gas mass density that are currently derived from spectral line scans. We combined a 117 deg2 dark matter lightcone from the Uchuu cosmological simulation with the simulated infrared dusty extragalactic sky (SIDES) approach. The clustering of the dusty galaxies in the SIDES-Uchuu product is validated by reproducing the cosmic infrared background anisotropies measured by Herschel and Planck. We find that in order to constrain the CO LF with an uncertainty below 20%, we need survey sizes of at least 0.1 deg2. Furthermore, accounting for the field-to-field variance using only the Poisson variance can underestimate the total variance by up to 80%. The lower the luminosity is and the larger the survey size is, the higher the level of underestimate. At z < 3, the impact of field-to-field variance on the cosmic molecular gas density can be as high as 40% for the 4.6 arcmin2 field, but drops below 10% for areas larger than 0.2 deg2. However, at z > 3 the variance decreases more slowly with survey size and for example drops below 10% for 1 deg2 fields. Finally, we find that the CO and [CII] LIM power spectra can vary by up to 50% in 1 deg2 fields. This limits the accuracy of the constraints provided by the first 1 deg2 surveys. In addition the level of the shot noise power is always dominated by the sources that are just below the detection thresholds, which limits its potential for deriving number densities of faint [CII] emitters. We provide an analytical formula to estimate the field-to-field variance of current or future LIM experiments given their observed frequency and survey size. The underlying code to derive the field-to-field variance and the full SIDES-Uchuu products (catalogs, cubes, and maps) are publicly available

CONCERTO: Extracting the power spectrum of the [C II ] emission line

International audienceCONCERTO is the first experiment to perform a [CII] line intensity mapping survey to target $z>5.2$. Measuring the [CII] power spectrum allows us to study the role of dusty star-forming galaxies in the star formation history during the Reionization and post-Reionization. The main obstacle to this measurement is the contamination by bright foregrounds. We evaluate our ability to retrieve the [CII] signal in mock observations using the Simulated Infrared Dusty Extragalactic Sky. We compared two methods for dealing with the dust continuum emission from galaxies: the standard PCA and the arPLS method. For line interlopers, the strategy relies on masking low-redshift galaxies using external catalogues. As we do not have observations of CO or classical CO proxies ,we relied on the COSMOS stellar mass catalogue. To measure the power spectrum of masked data, we adapted the P of K EstimatoR and discuss its use on LIM data. The arPLS method achieves a reduction of the continuum background to a sub-dominant level of the [CII] at z=7 by a factor of>70. When using PCA, this factor is only 0.7. The masking lowers the power amplitude of line contamination down to $2 \times 10^2 Jy^2/sr$ This residual level is dominated by faint undetected sources. For our [CII] model, this results in a detection at z = 5.2 with a power ratio [CII]/(residual interlopers) = $62 \pm 32$ for a 22 % area survey loss. However, at z = 7, [C II ] / (residual interlopers)$=2.0 \pm 1.4$. Thanks to the large area covered by SIDES-Uchuu, we show that the power amplitude of line residuals varies by 12-15% for z=5.2-7. We present an end-to-end simulation of the extragalactic foreground removal that we ran to detect the [CII] at high redshift via its power spectrum. We show that dust continuum emission are not a limiting foreground for [CII] LIM. Residual CO and [CI] limits our ability to measure the [CII] power spectrum at z>7

CONCERTO: High-fidelity simulation of millimeter line emissions of galaxies and [CII] intensity mapping

The intensity mapping of the [CII] 158um line redshifted to the sub-mm window is a promising probe of the z>4 star formation and its spatial distribution into the large-scale structure. To prepare the first-generation experiments (e.g., CONCERTO), we need realistic simulations of the sub-mm extragalactic sky in spectroscopy. We present a new version of the SIDES simulation including the main sub-mm lines around 1mm (CO, [CII], [CI]). This approach successfully reproduces the observed line luminosity functions. We then use our simulation to generate CONCERTO-like cubes (125-305GHz) and forecast the power spectra of the fluctuations caused by the various astrophysical components at those frequencies. Depending on our assumptions on the relation between star formation rate and [CII] luminosity, and the star formation history, our predictions of the z~6 [CII] power spectrum vary by two orders of magnitude. This highlights how uncertain the predictions are and how important future measurements will be to improve our understanding of this early epoch. SIDES can reproduce the CO shot noise recently measured at ~100 GHz by the mmIME experiment. Finally, we compare the contribution of the different astrophysical components at various redshift to the power spectra. The continuum is by far the brightest, by a factor of 3 to 100 depending on the frequency. At 300GHz, the CO foreground power spectrum is higher than the [CII] one for our base scenario. At lower frequency, the contrast between [CII] and extragalactic foregrounds is even worse. Masking the known galaxies from deep surveys should allow to reduce the foregrounds to 20% of the [CII] power spectrum up to z~6.5. However, this masking method will not be sufficient at higher redshifts. The code and the products of our simulation are released publicly and can be used for both intensity mapping experiments and sub-mm continuum and line surveys

CONCERTO: High-fidelity simulation of millimeter line emissions of galaxies and [CII] intensity mapping

The intensity mapping of the [CII] 158um line redshifted to the sub-mm window is a promising probe of the z>4 star formation and its spatial distribution into the large-scale structure. To prepare the first-generation experiments (e.g., CONCERTO), we need realistic simulations of the sub-mm extragalactic sky in spectroscopy. We present a new version of the SIDES simulation including the main sub-mm lines around 1mm (CO, [CII], [CI]). This approach successfully reproduces the observed line luminosity functions. We then use our simulation to generate CONCERTO-like cubes (125-305GHz) and forecast the power spectra of the fluctuations caused by the various astrophysical components at those frequencies. Depending on our assumptions on the relation between star formation rate and [CII] luminosity, and the star formation history, our predictions of the z~6 [CII] power spectrum vary by two orders of magnitude. This highlights how uncertain the predictions are and how important future measurements will be to improve our understanding of this early epoch. SIDES can reproduce the CO shot noise recently measured at ~100 GHz by the mmIME experiment. Finally, we compare the contribution of the different astrophysical components at various redshift to the power spectra. The continuum is by far the brightest, by a factor of 3 to 100 depending on the frequency. At 300GHz, the CO foreground power spectrum is higher than the [CII] one for our base scenario. At lower frequency, the contrast between [CII] and extragalactic foregrounds is even worse. Masking the known galaxies from deep surveys should allow to reduce the foregrounds to 20% of the [CII] power spectrum up to z~6.5. However, this masking method will not be sufficient at higher redshifts. The code and the products of our simulation are released publicly and can be used for both intensity mapping experiments and sub-mm continuum and line surveys

CONCERTO: Extracting the power spectrum of the [C II ] emission line

International audienceCONCERTO is the first experiment to perform a [CII] line intensity mapping survey to target $z>5.2$. Measuring the [CII] power spectrum allows us to study the role of dusty star-forming galaxies in the star formation history during the Reionization and post-Reionization. The main obstacle to this measurement is the contamination by bright foregrounds. We evaluate our ability to retrieve the [CII] signal in mock observations using the Simulated Infrared Dusty Extragalactic Sky. We compared two methods for dealing with the dust continuum emission from galaxies: the standard PCA and the arPLS method. For line interlopers, the strategy relies on masking low-redshift galaxies using external catalogues. As we do not have observations of CO or classical CO proxies ,we relied on the COSMOS stellar mass catalogue. To measure the power spectrum of masked data, we adapted the P of K EstimatoR and discuss its use on LIM data. The arPLS method achieves a reduction of the continuum background to a sub-dominant level of the [CII] at z=7 by a factor of>70. When using PCA, this factor is only 0.7. The masking lowers the power amplitude of line contamination down to $2 \times 10^2 Jy^2/sr$ This residual level is dominated by faint undetected sources. For our [CII] model, this results in a detection at z = 5.2 with a power ratio [CII]/(residual interlopers) = $62 \pm 32$ for a 22 % area survey loss. However, at z = 7, [C II ] / (residual interlopers)$=2.0 \pm 1.4$. Thanks to the large area covered by SIDES-Uchuu, we show that the power amplitude of line residuals varies by 12-15% for z=5.2-7. We present an end-to-end simulation of the extragalactic foreground removal that we ran to detect the [CII] at high redshift via its power spectrum. We show that dust continuum emission are not a limiting foreground for [CII] LIM. Residual CO and [CI] limits our ability to measure the [CII] power spectrum at z>7

CONCERTO: High-fidelity simulation of millimeter line emissions of galaxies and [CII] intensity mapping

The intensity mapping of the [CII] 158um line redshifted to the sub-mm window is a promising probe of the z>4 star formation and its spatial distribution into the large-scale structure. To prepare the first-generation experiments (e.g., CONCERTO), we need realistic simulations of the sub-mm extragalactic sky in spectroscopy. We present a new version of the SIDES simulation including the main sub-mm lines around 1mm (CO, [CII], [CI]). This approach successfully reproduces the observed line luminosity functions. We then use our simulation to generate CONCERTO-like cubes (125-305GHz) and forecast the power spectra of the fluctuations caused by the various astrophysical components at those frequencies. Depending on our assumptions on the relation between star formation rate and [CII] luminosity, and the star formation history, our predictions of the z~6 [CII] power spectrum vary by two orders of magnitude. This highlights how uncertain the predictions are and how important future measurements will be to improve our understanding of this early epoch. SIDES can reproduce the CO shot noise recently measured at ~100 GHz by the mmIME experiment. Finally, we compare the contribution of the different astrophysical components at various redshift to the power spectra. The continuum is by far the brightest, by a factor of 3 to 100 depending on the frequency. At 300GHz, the CO foreground power spectrum is higher than the [CII] one for our base scenario. At lower frequency, the contrast between [CII] and extragalactic foregrounds is even worse. Masking the known galaxies from deep surveys should allow to reduce the foregrounds to 20% of the [CII] power spectrum up to z~6.5. However, this masking method will not be sufficient at higher redshifts. The code and the products of our simulation are released publicly and can be used for both intensity mapping experiments and sub-mm continuum and line surveys