ZFOURGE: Extreme 5007A˚\AA emission may be a common early-lifetime phase for star-forming galaxies at z>2.5z > 2.5

Using the \prospector\ spectral energy distribution (SED) fitting code, we analyze the properties of 19 Extreme Emission Line Galaxies (EELGs) identified in the bluest composite SED in the \zfourge\ survey at $2.5 \leq z \leq 4$. \prospector\ includes a physical model for nebular emission and returns probability distributions for stellar mass, stellar metallicity, dust attenuation, and nonparametric star formation history (SFH). The EELGs show evidence for a starburst in the most recent 50 Myr, with the median EELG having a specific star formation rate (sSFR) of 4.6 Gyr$^{-1}$ and forming 15\% of its mass in this short time. For a sample of more typical star-forming galaxies (SFGs) at the same redshifts, the median SFG has a sSFR of 1.1 Gyr$^{-1}$ and forms only $4\%$ of its mass in the last 50 Myr. We find that virtually all of our EELGs have rising SFHs, while most of our SFGs do not. From our analysis, we hypothesize that many, if not most, star-forming galaxies at $z \geq 2.5$ undergo an extreme H$\beta$+[\hbox{{\rm O}\kern 0.1em{\sc iii}}] emission line phase early in their lifetimes. In a companion paper, we obtain spectroscopic confirmation of the EELGs as part of our {\sc MOSEL} survey. In the future, explorations of uncertainties in modeling the UV slope for galaxies at $z>2$ are needed to better constrain their properties, e.g. stellar metallicities.Comment: 11 pages, 5 figures (main figure is fig 5), accepted for publication in Ap

SPECULATOR: Emulating stellar population synthesis for fast and accurate galaxy spectra and photometry

We present SPECULATOR - a fast, accurate, and flexible framework for emulating stellar population synthesis (SPS) models for predicting galaxy spectra and photometry. For emulating spectra, we use principal component analysis to construct a set of basis functions, and neural networks to learn the basis coefficients as a function of the SPS model parameters. For photometry, we parameterize the magnitudes (for the filters of interest) as a function of SPS parameters by a neural network. The resulting emulators are able to predict spectra and photometry under both simple and complicated SPS model parameterizations to percent-level accuracy, giving a factor of $10^3$-$10^4$ speed up over direct SPS computation. They have readily-computable derivatives, making them amenable to gradient-based inference and optimization methods. The emulators are also straightforward to call from a GPU, giving an additional order-of-magnitude speed-up. Rapid SPS computations delivered by emulation offers a massive reduction in the computational resources required to infer the physical properties of galaxies from observed spectra or photometry and simulate galaxy populations under SPS models, whilst maintaining the accuracy required for a range of applications

Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer

International audienceBackground: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. Methods: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. Results: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. Conclusion: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial

Phase I trial of oxaliplatin with fluorouracil, folinic acid and concurrent radiotherapy for oesophageal cancer

This dose escalation study was designed to determine the maximum tolerated dose (MTD) and recommended doses (RDs) of 5-fluorouracil (5FU), folinic acid and oxaliplatin (FOLFOX) with concomitant radiotherapy in inoperable/metastatic oesophageal squamous cell carcinoma or adenocarcinoma. Patients received three courses of LV5FU2 regimen (folinic acid 200 mg m−2, bolus 5FU 300–400 mg/m2, continuous infusion 5FU 400–600 mg m−2 on days 1 and 2) and escalating doses of oxaliplatin 50 to 100 mg m−2 on day 1 (FOLFOX). This regimen was repeated every 2 weeks, concomitant to a 50-gray radiotherapy per 5 weeks. Three more cycles were delivered after completion of radiation therapy. Three to six patients were allocated to each of the five dose levels until MTD was reached. Thirty-three patients were enroled and 21 had metastatic disease. Maximum tolerated dose was oxaliplatin 100 mg m−2, and continuous infusion 5FU was 600 mg m−2 day− (level 5). The most common toxicities were neutropenia, dysphagia and oesophagitis. The RDs were those of FOLFOX-4 regimen (oxaliplatin 85 mg m−2 and full doses of LV5FU2). The overall response was 48.5%, including 12% complete response. Response rate on primary tumour was 62.9%. This FOLFOX-4 regimen was reasonably well tolerated and effective in inoperable/metastatic oesophageal carcinoma and warrants additional investigation

A fast radio burst localized to a massive galaxy

Intense, millisecond-duration bursts of radio waves (named fast radio bursts) have been detected from beyond the Milky Way. Their dispersion measures—which are greater than would be expected if they had propagated only through the interstellar medium of the Milky Way—indicate extragalactic origins and imply contributions from the intergalactic medium and perhaps from other galaxies. Although several theories exist regarding the sources of these fast radio bursts, their intensities, durations and temporal structures suggest coherent emission from highly magnetized plasma. Two of these bursts have been observed to repeat, and one repeater (FRB 121102) has been localized to the largest star-forming region of a dwarf galaxy at a cosmological redshift of 0.19 (refs. 7,8,9). However, the host galaxies and distances of the hitherto non-repeating fast radio bursts are yet to be identified. Unlike repeating sources, these events must be observed with an interferometer that has sufficient spatial resolution for arcsecond localization at the time of discovery. Here we report the localization of a fast radio burst (FRB 190523) to a few-arcsecond region containing a single massive galaxy at a redshift of 0.66. This galaxy is different from the host of FRB 121102, as it is a thousand times more massive, with a specific star-formation rate (the star-formation rate divided by the mass) a hundred times smaller

Development and Psychometric Evaluation of an Item Bank for Computerized Adaptive Testing of the EORTC Insomnia Dimension in Cancer Patients (EORTC CAT-SL)

To further advance assessment of patient-reported outcomes, the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Group has developed computerized adaptive test (CAT) versions of all EORTC Quality of Life Core Questionnaire (QLQ-C30) scales/items. The aim of this study was to develop and evaluate an item bank for CAT measurement of insomnia (CAT-SL). In line with the EORTC guidelines, the developmental process comprised four phases: (I) defining the concept insomnia and literature search, (II) selection and formulation of new items, (III) pre-testing and (IV) field-testing, including psychometric analyses of the final item bank. In phase I, the literature search identified 155 items that were compatible with our conceptualisation of insomnia, including both quantity and quality of sleep. In phase II, following a multistep-approach, this number was reduced to 15 candidate items. Pre-testing of these items in cancer patients (phase III) resulted in an item list of 14 items, which were field-tested among 1094 patients in phase IV. Psychometric evaluations showed that eight items could be retained in a unidimensional model. The final item bank yielded greater measurement precision than the original QLQ-C30 insomnia item. It was estimated that administering two or more items from the insomnia item bank with CAT results in a saving in sample size between approximately 15–25%. The 8-item EORTC CAT-SL item bank facilitates precise and efficient measurement of insomnia as part of the EORTC CAT system of health-related quality life assessment in both clinical research and practice

Conserved Molecular Underpinnings and Characterization of a Role for Caveolin-1 in the Tumor Microenvironment of Mature T-Cell Lymphomas

Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4+ and CD8+ T-cell controls (n = 52). From these results, we sought to characterize a role for caveolin-1 (CAV1), a gene with previous description in the progression of both solid and hematological tumors. Caveolin-1 was upregulated, albeit with a heterogeneous nature, across all mature T-cell lymphoma subtypes, a finding confirmed using immunohistochemical staining on an independent sampling of mature T-cell lymphoma biopsies (n = 65 cases). Further, stratifying malignant samples in accordance with high and low CAV1 expression revealed that higher expression of CAV1 in mature T-cell lymphomas is analogous with an enhanced inflammatory and invasive gene expression profile. Taken together, these results demonstrate a role for CAV1 in the tumor microenvironment of mature T-cell malignancies and point toward potential prognostic implications

Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/? cetuximab in oesophageal cancer

Background: The SCOPE-1 study tested the role of adding cetuximab to conventional definitive chemoradiotherapy (dCRT), and demonstrated greater toxicity and worse survival outcomes. We present the long-term outcomes and patterns of recurrence. Methods: SCOPE-1 was a phase II/III trial in which patients were randomised to cisplatin 60mgm�2 (day 1) and capecitabine 625mgm�2 bd (days 1–21) for four cycles þ/� cetuximab 400mgm�2 day 1 then by 250mgm�2 weekly. Radiotherapy consisted of 50 Gy/25# given concurrently with cycles 3 and 4. Recruitment was between February 2008 and February 2012, when the IDMC recommended closure on the basis of futility. Results: About 258 patients (dCRT¼129; dCRTþcetuximab (dCRTþC)¼129) were recruited from 36 centres. About 72.9% (n¼188) had squamous cell histology. The median follow-up (IQR) was 46.2 (35.9–48.3) months for surviving patients. The median overall survival (OS; months; 95% CI) was 34.5 (24.7–42.3) in dCRT and 24.7 (18.6–31.3) in dCRTþC (hazard ratio (HR)¼1.25, 95% CIs: 0.93–1.69, P¼0.137). Median progression-free survival (PFS; months; 95% CI) was 24.1 (15.3–29.9) and 15.9 (10.7–20.8) months, respectively (HR¼1.28, 95% CIs: 0.94–1.75; P¼0.114). On multivariable analysis only earlier stage, full-dose RT, and higher cisplatin dose intensity were associated with improved OS. Conclusions: The mature analysis demonstrates that the dCRT regimen used in the study provided useful survival outcomes despite its use in patients who were largely unfit for surgery or who had inoperable disease. Given the competing risk of systemic and local failure, future studies should continue to focus on enhancing local control as well as optimising systemic therapy

Measurement of the tt¯tt¯ production cross section in pp collisions at √s=13 TeV with the ATLAS detector

A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb