Abstract Background RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus ...bevacizumab in patients with RAS -mutant tumours needs to be further evaluated. Whether to treat patients with BRAF -mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. Methods Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations. Survival analysis was done using Kaplan–Meier estimation and differences were expressed using the log-rank test. Overall response rate (ORR) was compared using Fisher's exact test. Data from a central independent radiological response evaluation were used to calculate early tumour shrinkage (ETS) and depth of response (DpR). Results Overall, 188 patients with RAS -mutant tumours and 48 with BRAF -mutant tumours were identified. In BRAF -mutant patients, ORR was numerically higher in the cetuximab versus the bevacizumab arm (52% versus 40%), while comparable results were achieved for progression-free survival (PFS; hazard ratio HR = 0.84, p = 0.56) and overall survival (OS; HR 0.79, p = 0.45). RAS mutation was associated with a trend towards lower ORR (37% versus 50.5%, p = 0.11) and shorter PFS (7.4 versus 9.7 months; HR 1.25; p = 0.14) in patients receiving FOLFIRI plus cetuximab versus bevacizumab, but OS was comparable (19.1 versus 20.1 months; HR 1.05; p = 0.73), respectively. ETS identified subgroups sensitive to cetuximab-based treatment in both BRAF - (9/17) and RAS -mutant (18/48) patients and was associated with significantly longer OS. DpR was comparable between both treatment arms in RAS - and BRAF -mutant patients, respectively. Conclusions In BRAF - and RAS -mutant patients, cetuximab- and bevacizumab-based treatment had comparable survival times. ETS represents an early parameter associated with the benefit from anti-EGFR, while this was not the case with vascular endothelial growth factor A blockade.
We present an analysis of the final data release of the Carnegie Supernova Project I, focusing on the absolute calibration of the luminosity-decline rate relation for Type Ia supernovae (SNe Ia) ...using new intrinsic color relations with respect to the color-stretch parameter, sBV, enabling improved dust extinction corrections. We investigate to what degree the so-called fast-declining SNe Ia can be used to determine accurate extragalactic distances. We estimate the intrinsic scatter in the luminosity-decline rate relation and find it ranges from 0.13 mag to 0.18 mag with no obvious dependence on wavelength. Using the Cepheid variable star data from the SH0ES project, the SN Ia distance scale is calibrated and the Hubble constant is estimated using our optical and near-infrared sample, and these results are compared to those determined exclusively from a near-infrared subsample. The systematic effect of the supernova's host galaxy mass is investigated as a function of wavelength and is found to decrease toward redder wavelengths, suggesting this effect may be due to dust properties of the host. Using estimates of the dust extinction derived from optical and near-infrared wavelengths and applying these to the H band, we derive a Hubble constant , whereas using a simple B − V color correction applied to the B band yields . Photometry of two calibrating SNe Ia from the CSP-II sample, SN 2012ht and SN 2015F, is presented and used to improve the calibration of the SN Ia distance ladder.
The Carnegie Supernova Project (CSP) is a five-year survey being carried out at the Las Campanas Observatory to obtain high-quality light curves of ~100 low-redshift Type Ia supernovae (SNe Ia) in a ...well-defined photometric system. Here we present the first release of photometric data that contains the optical light curves of 35 SNe Ia, and near-infrared light curves for a subset of 25 events. The data comprise 5559 optical (ugriBV) and 1043 near-infrared (Y JHKs ) data points in the natural system of the Swope telescope. Twenty-eight SNe have pre-maximum data, and for 15 of these, the observations begin at least 5 days before B maximum. This is one of the most accurate data sets of low-redshift SNe Ia published to date. When completed, the CSP data set will constitute a fundamental reference for precise determinations of cosmological parameters, and serve as a rich resource for comparison with models of SNe Ia.
An analysis of the first set of low-redshift (z < 0.08) Type Ia supernovae (SNe Ia) monitored by the Carnegie Supernova Project between 2004 and 2006 is presented. The data consist of well-sampled, ...high-precision optical (ugriBV) and near-infrared (NIR; YJHKs ) light curves in a well-understood photometric system. Methods are described for deriving light-curve parameters, and for building template light curves which are used to fit SN Ia data in the ugriBVYJH bands. The intrinsic colors at maximum light are calibrated using a subsample of supernovae (SNe) assumed to have suffered little or no reddening, enabling color excesses to be estimated for the full sample. The optical-NIR color excesses allow the properties of the reddening law in the host galaxies to be studied. A low average value of the total-to-selective absorption coefficient, RV 1.7, is derived when using the entire sample of SNe. However, when the two highly reddened SNe (SN 2005A and SN 2006X) in the sample are excluded, a value RV 3.2 is obtained, similar to the standard value for the Galaxy. The red colors of these two events are well matched by a model where multiple scattering of photons by circumstellar dust steepens the effective extinction law. The absolute peak magnitudes of the SNe are studied in all bands using a two-parameter linear fit to the decline rates and the colors at maximum light, or alternatively, the color excesses. In both cases, similar results are obtained with dispersions in absolute magnitudes of 0.12-0.16 mag, depending on the specific filter-color combination. In contrast to the results obtained from the comparison of the color excesses, these fits of absolute magnitude give RV 1-2 when the dispersion is minimized, even when the two highly reddened SNe are excluded. This discrepancy suggests that, beyond the 'normal' interstellar reddening produced in the host galaxies, there is an intrinsic dispersion in the colors of SNe Ia which is correlated with luminosity but independent of the decline rate. Finally, a Hubble diagram for the best-observed subsample of SNe is produced by combining the results of the fits of absolute magnitude versus decline rate and color excess for each filter. The resulting scatter of 0.12 mag appears to be limited by the peculiar velocities of the host galaxies as evidenced by the strong correlation between the distance-modulus residuals observed in the individual filters. The implication is that the actual precision of SNe Ia distances is 3%-4%.
Background/objectives
Probiotics are living microorganisms that confer a health benefit on the host when administered. This systematic review and meta-analysis investigates the efficacy and safety of ...probiotics in adult and paediatric patients diagnosed with cancer.
Methods
A systematic review and meta-analysis was undertaken (PROSPERO registration: CRD42016050252). Randomised controlled trials (RCT), identified through screening multiple databases were included for analysis of efficacy. Non-randomised controlled trials and case reports were included for safety analysis. Outcomes included the reduction in the incidence and severity of diarrhoea, and adverse events. Where possible, data were combined for meta-analysis using a random-effects model. Planned subgroup analyses were not possible through marked heterogeneity of study characteristics.
Results
Twenty one studies (
N
= 2982 participants) were included for assessment of efficacy. Probiotics may reduce the incidence of diarrhoea in patients with cancer odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.34–0.78, 95% prediction interval (PI) 0.3–0.92, I-sq 36.9%, 5 studies and the duration of pyrexia standardised mean difference 0.39 days, 95% CI 0.35–0.43, I-sq 0.01%, 5 studies. Twenty five studies (
N
= 2242) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. Definitions and reporting of adverse events were variable and inconsistent.
Conclusions
There remain insufficient studies to assess the true effect of probiotics in people with cancer. Meta-analysis suggests probiotics may be beneficial but further studies are still required. Improved reporting of outcomes and adverse events in clinical trials are required to improve accuracy and confidence of conclusions drawn in future updates.
Observations spanning a large wavelength range, from X-ray to radio, of the Type IIb supernova (SN) 2011hs are presented, covering its evolution during the first year after explosion. The optical ...light curve presents a narrower shape and a fainter luminosity at peak than previously observed for Type IIb SNe. High expansion velocities are measured from the broad absorption H i and He i lines. From the comparison of the bolometric light curve and the time evolution of the photospheric velocities with hydrodynamical models, we found that SN 2011hs is consistent with the explosion of a 3-4 M He-core progenitor star, corresponding to a main-sequence mass of 12-15 M, that ejected a mass of 56Ni of about 0.04 M, with an energy of E = 8.5 × 1050 ERG. Such a low-mass progenitor scenario is in full agreement with the modelling of the nebular spectrum taken at ∼215 d from maximum. From the modelling of the adiabatic cooling phase, we infer a progenitor radius of 500-600 R, clearly pointing to an extended progenitor star. The radio light curve of SN 2011hs yields a peak luminosity similar to that of SN 1993J, but with a higher mass-loss rate and a wind density possibly more similar to that of SN 2001ig. Although no significant deviations from a smooth decline have been found in the radio light curves, we cannot rule out the presence of a binary companion star.
Observations by the Shallow Radar instrument on Mars Reconnaissance Orbiter reveal several deposits of buried CO2 ice within the south polar layered deposits. Here we present mapping that ...demonstrates this unit is 18% larger than previously estimated, containing enough mass to double the atmospheric pressure on Mars if sublimated. We find three distinct subunits of CO2 ice, each capped by a thin (10–60 m) bounding layer (BL). Multiple lines of evidence suggest that each BL is dominated by water ice. We model the history of CO2 accumulation at the poles based on obliquity and insolation variability during the last 1 Myr assuming a total mass budget consisting of the current atmosphere and the sequestered ice. Our model predicts that CO2 ice has accumulated over large areas several times during that period, in agreement with the radar findings of multiple periods of accumulation.
Key Points
Mars' south polar cap contains a deposit with enough CO2 to double the atmospheric pressure if it sublimated
Surface and radar observations show this deposit to be three CO2 subunits capped by water ice
Modeling allows us to constrain the minimum age of this deposit to be ∼300 kyr old
Stars that explode as supernovae come in two main classes. A type Ia supernova is recognized by the absence of hydrogen and the presence of elements such as silicon and sulphur in its spectrum; this ...class of supernova is thought to produce the majority of iron-peak elements in the Universe. They are also used as precise 'standard candles' to measure the distances to galaxies. While there is general agreement that a type Ia supernova is produced by an exploding white dwarf star, no progenitor system has ever been directly observed. Significant effort has gone into searching for circumstellar material to help discriminate between the possible kinds of progenitor systems, but no such material has hitherto been found associated with a type Ia supernova. Here we report the presence of strong hydrogen emission associated with the type Ia supernova SN2002ic, indicating the presence of large amounts of circumstellar material. We infer from this that the progenitor system contained a massive asymptotic-giant-branch star that lost several solar masses of hydrogen-rich gas before the supernova explosion.
We present an updated analysis of the intrinsic colors of Type Ia supernova (SNe Ia) using the latest data release of the Carnegie Supernova Project. We introduce a new light-curve parameter very ...similar to stretch that is better suited for fast-declining events, and find that these peculiar types can be seen as extensions to the population of "normal" SNe Ia. With a larger number of objects, an updated fit to the Lira relation is presented along with evidence for a dependence on the late-time slope of the B - V light-curves with stretch and color. Using the full wavelength range from u to H band, we place constraints on the reddening law for the sample as a whole and also for individual events/hosts based solely on the observed colors. The photometric data continue to favor low values of R sub(V), though with large variations from event to event, indicating an intrinsic distribution. We confirm the findings of other groups that there appears to be a correlation between the derived reddening law, R sub(V), and the color excess, E(B - V), such that larger E(B - V) tends to favor lower R sub(V). The intrinsic u-band colors show a relatively large scatter that cannot be explained by variations in R sub(V) or by the Goobar power-law for circumstellar dust, but rather is correlated with spectroscopic features of the supernova and is therefore likely due to metallicity effects.
Abstract
We present detailed ultraviolet, optical, and near-infrared light curves of the Type Ia supernova (SN) 2012fr, which exploded in the Fornax cluster member NGC 1365. These precise ...high-cadence light curves provide a dense coverage of the flux evolution from −12 to +140 days with respect to the epoch of
B
-band maximum (
t
B
max
). Supplementary imaging at the earliest epochs reveals an initial slow and nearly linear rise in luminosity with a duration of ∼2.5 days, followed by a faster rising phase that is well reproduced by an explosion model with a moderate amount of
56
Ni mixing in the ejecta. From our analysis of the light curves, we conclude that: (i) the explosion occurred <22 hr before the first detection of the supernova, (ii) the rise time to peak bolometric (
λ
> 1800 Å) luminosity was 16.5 ± 0.6 days, (iii) the supernova suffered little or no host-galaxy dust reddening, (iv) the peak luminosity in both the optical and near-infrared was consistent with the bright end of normal Type Ia diversity, and (v) 0.60 ± 0.15
M
⊙
of
56
Ni was synthesized in the explosion. Despite its normal luminosity, SN 2012fr displayed unusually prevalent high-velocity Ca
ii
and Si
ii
absorption features, and a nearly constant photospheric velocity of the Si
ii
λ
6355 line at ∼12,000
km
s
−
1
that began ∼5 days before
t
B
max
. We also highlight some of the other peculiarities in the early phase photometry and the spectral evolution. SN 2012fr also adds to a growing number of Type Ia supernovae that are hosted by galaxies with direct Cepheid distance measurements.
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