The Galaxy And Mass Assembly (GAMA) survey is one of the largest contemporary spectroscopic surveys of low redshift galaxies. Covering an area of ∼286 deg2 (split among five survey regions) down to a ...limiting magnitude of r < 19.8 mag, we have collected spectra and reliable redshifts for 238 000 objects using the AAOmega spectrograph on the Anglo-Australian Telescope. In addition, we have assembled imaging data from a number of independent surveys in order to generate photometry spanning the wavelength range 1 nm–1 m. Here, we report on the recently completed spectroscopic survey and present a series of diagnostics to assess its final state and the quality of the redshift data. We also describe a number of survey aspects and procedures, or updates thereof, including changes to the input catalogue, redshifting and re-redshifting, and the derivation of ultraviolet, optical and near-infrared photometry. Finally, we present the second public release of GAMA data. In this release, we provide input catalogue and targeting information, spectra, redshifts, ultraviolet, optical and near-infrared photometry, single-component Sérsic fits, stellar masses, Hα-derived star formation rates, environment information, and group properties for all galaxies with r < 19.0 mag in two of our survey regions, and for all galaxies with r < 19.4 mag in a third region (72 225 objects in total). The data base serving these data is available at http://www.gama-survey.org/.
We use a highly complete subset of the Galaxy And Mass Assembly II (GAMA-II) redshift sample to fully describe the stellar mass dependence of close pairs and mergers between 108 and 1012 M⊙. Using ...the analytic form of this fit we investigate the total stellar mass accreting on to more massive galaxies across all mass ratios. Depending on how conservatively we select our robust merging systems, the fraction of mass merging on to more massive companions is 2.0–5.6 per cent. Using the GAMA-II data we see no significant evidence for a change in the close pair fraction between redshift z = 0.05 and 0.2. However, we find a systematically higher fraction of galaxies in similar mass close pairs compared to published results over a similar redshift baseline. Using a compendium of data and the function γ
M
= A(1 + z)
m
to predict the major close pair fraction, we find fitting parameters of A = 0.021 ± 0.001 and m = 1.53 ± 0.08, which represents a higher low-redshift normalization and shallower power-law slope than recent literature values. We find that the relative importance of in situ star formation versus galaxy merging is inversely correlated, with star formation dominating the addition of stellar material below
$\mathcal {M}^*$
and merger accretion events dominating beyond
$\mathcal {M}^*$
. We find mergers have a measurable impact on the whole extent of the galaxy stellar mass function (GSMF), manifest as a deepening of the ‘dip’ in the GSMF over the next ∼Gyr and an increase in
$\mathcal {M}^*$
by as much as 0.01–0.05 dex.
The treatment of cancer is being revolutionized by an improved understanding of the genetic events that occur in tumors. Advances in the understanding of the prevalence and patterns of mutations in ...melanoma have recently led to impressive results in trials of personalized, targeted therapies for this disease. In this review, we will discuss the molecular targets that have been validated clinically, additional genetic events that are candidates for future trials, and the challenges that remain to improve outcomes further in this aggressive disease.
Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs) and only one ...has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients.
Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were retrospectively identified.
One hundred and nineteen patients from 13 academic tertiary referral centers were treated with anti-PD-1. In patients with preexisting AD (N=52), the response rate was 33%. 20 (38%) patients had a flare of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren’s syndrome, 2/2 with immune thrombocytopaenic purpura and 3/8 with psoriasis. No patients with gastrointestinal (N=6) or neurological disorders (N=5) flared. Only 2 (4%) patients discontinued treatment due to flare, but 15 (29%) developed other irAEs and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs requiring immunosuppression (N=67) the response rate was 40%. Two (3%) patients had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs (14, 21% grade 3–4) and 8 (12%) discontinued treatment. There were no treatment-related deaths.
In melanoma patients with preexisting ADs or major irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities, but these were often mild, easily managed and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses. The results support that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting ADs or prior major irAEs with ipilimumab.
Context.
On 2020 April 19 a coronal mass ejection (CME) was detected in situ by Solar Orbiter at a heliocentric distance of about 0.8 AU. The CME was later observed in situ on April 20 by the Wind ...and BepiColombo spacecraft whilst BepiColombo was located very close to Earth. This CME presents a good opportunity for a triple radial alignment study, as the spacecraft were separated by less than 5° in longitude. The source of the CME, which was launched on April 15, was an almost entirely isolated streamer blowout. The Solar Terrestrial Relations Observatory (STEREO)-A spacecraft observed the event remotely from −75.1° longitude, which is an exceptionally well suited viewpoint for heliospheric imaging of an Earth directed CME.
Aims.
The configuration of the four spacecraft has provided an exceptionally clean link between remote imaging and in situ observations of the CME. We have used the in situ observations of the CME at Solar Orbiter, Wind, and BepiColombo and the remote observations of the CME at STEREO-A to determine the global shape of the CME and its evolution as it propagated through the inner heliosphere.
Methods.
We used three magnetic flux rope models that are based on different assumptions about the flux rope morphology to interpret the large-scale structure of the interplanetary CME (ICME). The 3DCORE model assumes an elliptical cross-section with a fixed aspect-ratio calculated by using the STEREO Heliospheric Imager (HI) observations as a constraint. The other two models are variants of the kinematically-distorted flux rope (KFR) technique, where two flux rope cross-sections are considered: one in a uniform solar wind and another in a solar-minimum-like structured solar wind. Analysis of CME evolution has been complemented by the use of (1) the ELEvoHI model to compare predicted CME arrival times and confirm the connection between the imaging and in situ observations, and (2) the PREDSTORM model, which provides an estimate of the
Dst
index at Earth using Solar Orbiter magnetometer data as if it were a real–time upstream solar wind monitor.
Results.
A clear flattening of the CME cross-section has been observed by STEREO-A, and further confirmed by comparing profiles of the flux rope models to the in situ data, where the distorted flux rope cross-section qualitatively agrees most with in situ observations of the magnetic field at Solar Orbiter. Comparing in situ observations of the magnetic field between spacecraft, we find that the dependence of the maximum (mean) magnetic field strength decreases with heliocentric distance as
r
−1.24 ± 0.50
(
r
−1.12 ± 0.14
), which is in disagreement with previous studies. Further assessment of the axial and poloidal magnetic field strength dependencies suggests that the expansion of the CME is likely neither self-similar nor cylindrically symmetric.
Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in ...BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after≥36-month follow-up for all living patients.
This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150mg twice daily) plus trametinib (2mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics.
Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n= 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and<3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use.
These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.
The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes ...likely to arise on short time-scales and be directly related to the galaxy–galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different time-scales for pair galaxies, targeting numerous star- formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries are consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-duration SFR indicators (e.g. Hα), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs.
Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time‐dependent confounding affected by prior treatment ...when faced with long follow‐up times, multiple time‐varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow‐up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, ie, it is doubly robust, and can yield valid inference when used in conjunction with machine learning. It also has the advantage of easy‐to‐calculate analytic standard errors in contrast to the g‐formula, which requires bootstrapping. We use a topical and sophisticated question from HIV treatment research to show that LTMLE can be used successfully in complex realistic settings, and we compare results to competing estimators. Our example illustrates the following practical challenges common to many epidemiological studies: (1) long follow‐up time (30 months); (2) gradually declining sample size; (3) limited support for some intervention rules of interest; (4) a high‐dimensional set of potential adjustment variables, increasing both the need and the challenge of integrating appropriate machine learning methods; and (5) consideration of collider bias. Our analyses, as well as simulations, shed new light on the application of LTMLE in complex and realistic settings: We show that (1) LTMLE can yield stable and good estimates, even when confronted with small samples and limited modeling options; (2) machine learning utilized with a small set of simple learners (if more complex ones cannot be fitted) can outperform a single, complex model, which is tailored to incorporate prior clinical knowledge; and (3) performance can vary considerably depending on interventions and their support in the data, and therefore critical quality checks should accompany every LTMLE analysis. We provide guidance for the practical application of LTMLE.
We present the Lambda Adaptive Multi-Band Deblending Algorithm in R (lambdar), a novel code for calculating matched aperture photometry across images that are neither pixel- nor PSF-matched, using ...prior aperture definitions derived from high-resolution optical imaging. The development of this program is motivated by the desire for consistent photometry and uncertainties across large ranges of photometric imaging, for use in calculating spectral energy distributions. We describe the program, specifically key features required for robust determination of panchromatic photometry: propagation of apertures to images with arbitrary resolution, local background estimation, aperture normalization, uncertainty determination and propagation, and object deblending. Using simulated images, we demonstrate that the program is able to recover accurate photometric measurements in both high-resolution, low-confusion, and low-resolution, high-confusion, regimes. We apply the program to the 21-band photometric data set from the Galaxy And Mass Assembly (GAMA) Panchromatic Data Release (PDR; Driver et al. 2016), which contains imaging spanning the far-UV to the far-IR. We compare photometry derived from lambdar with that presented in Driver et al. (2016), finding broad agreement between the data sets. None the less, we demonstrate that the photometry from lambdar is superior to that from the GAMA PDR, as determined by a reduction in the outlier rate and intrinsic scatter of colours in the lambdar data set. We similarly find a decrease in the outlier rate of stellar masses and star formation rates using lambdar photometry. Finally, we note an exceptional increase in the number of UV and mid-IR sources able to be constrained, which is accompanied by a significant increase in the mid-IR colour–colour parameter-space able to be explored.
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