Lurbinectedin (PM01183) has synergistic antitumor activity when combined with doxorubicin in mice with xenografted tumors. This phase I trial determined the recommended dose (RD) of doxorubicin ...(bolus) and PM01183 (1-h intravenous infusion) on day 1 every 3 weeks (q3wk), and obtained preliminary evidence of antitumor activity for this combination in small-cell lung cancer (SCLC).
Patients with advanced solid tumors received doxorubicin and PM01183 following a standard dose escalation design and expansion at the RD. Twenty-seven patients had relapsed SCLC: 12 with sensitive disease (platinum-free interval ≥90 days) and 15 with resistant disease (platinum-free interval <90 days).
Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose was the RD. In relapsed SCLC, treatment tolerance at the RD was manageable. Transient and reversible myelosuppression (including neutropenia, thrombocytopenia, and febrile neutropenia) was the main toxicity, managed with dose adjustment and colony-stimulating factors. Fatigue (79%), nausea/vomiting (58%), decreased appetite (53%), mucositis (53%), alopecia (42%), diarrhea/constipation (42%), and asymptomatic creatinine (68%) and transaminase increases (alanine aminotransferase 42%; aspartate aminotransferase 32%) were common, and mostly mild or moderate. Complete (n = 2, 8%) and partial response (n = 13, 50%) occurred in relapsed SCLC, mostly at the RD. Response rates at second line were 91.7% in sensitive disease median progression-free survival (PFS)=5.8 months and 33.3% in resistant disease (median PFS = 3.5 months). At third line, response rate was 20.0% (median PFS = 1.2 months), all in resistant disease.
Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose on day 1 q3wk has shown remarkable activity, mainly in second line, with manageable tolerance in relapsed SCLC, leading to further evaluation of this combination within an ongoing phase III trial.
Aims. Our goal is to characterise the dependence of the optical mass-to-light ratio on galaxy colour up to z = 1.5, expanding the redshift range explored in previous work. Methods. From the ...redshifts, stellar masses, and rest-frame luminosities of the ALHAMBRA multi-filter survey, we derive the mass-to-light ratio versus colour relation for quiescent and for star-forming galaxies. The intrinsic relation and its physical dispersion are derived with a Bayesian inference model. Results. The rest-frame i-band mass-to-light ratio of quiescent and star-forming galaxies presents a tight correlation with the rest-frame (g − i) colour up to z = 1.5. The mass-to-light ratio versus colour relation is linear for quiescent galaxies and quadratic for star-forming galaxies. The intrinsic dispersion in these relations is 0.02 dex for quiescent galaxies and 0.06 dex for star-forming ones. The derived relations do not present a significant redshift evolution and are compatible with previous local results in the literature. Finally, these tight relations also hold for g- and r-band luminosities. Conclusions. The derived mass-to-light ratio versus colour relations in ALHAMBRA can be used to predict the mass-to-light ratio from a rest-frame optical colour up to z = 1.5. These tight correlations do not change with redshift, suggesting that galaxies have evolved along the derived relations during the last 9 Gyr.
The Javalambre-Physics of the Accelerating Universe Astrophysical Survey (J-PAS) will observe approximately one-third of the northern sky with a set of 56 narrow-band filters using the dedicated 2.55 ...m Javalambre Survey Telescope (JST) at the Javalambre Astrophysical Observatory. Prior to the installation of the main camera, in order to demonstrate the scientific potential of J-PAS, two small surveys were performed with the single-CCD Pathfinder camera: miniJPAS (~1 deg
2
along the Extended Groth Strip), and J-NEP (~0.3 deg
2
around the JWST North Ecliptic Pole Time Domain Field), including all 56 J-PAS filters as well as
u
,
g
,
r
, and
i
. J-NEP is ~0.5–1.0 mag deeper than miniJPAS, providing photometry for 24,618
r
-band-detected sources and photometric redshifts (photo-
z
) for the 6662 sources with
r
< 23. In this paper, we describe the photometry and photo-
z
of J-NEP and demonstrate a new method for the removal of systematic offsets in the photometry based on the median colours of galaxies, which we call ‘galaxy locus recalibration’. This method does not require spectroscopic observations except in a few reference pointings and, unlike previous methods, is directly applicable to the whole J-PAS survey. We use a spectroscopic sample of 787 galaxies to test the photo-
z
performance for J-NEP and in comparison to miniJPAS. We find that the deeper J-NEP observations result in a factor ~1.5–2 decrease in
σ
NMAD
(a robust estimate of the standard deviation of the photo-
z
error) and
η
(the outlier rate) relative to miniJPAS for
r
> 21.5 sources, but no improvement in brighter ones, which is probably because of systematic uncertainties. We find the same relation between
σ
NMAD
and
odds
in J-NEP and miniJPAS, which suggests that we will be able to predict the
σ
NMAD
of any set of J-PAS sources from their
odds
distribution alone, with no need for additional spectroscopy to calibrate the relation. We explore the causes of photo-
z
outliers and find that colour-space degeneracy at low S/N, photometry artefacts, source blending, and exotic spectra are the most important factors.
Aims. Long gamma-ray bursts (LGRBs) are associated with the deaths of massive stars and might therefore be a potentially powerful tool for tracing cosmic star formation. However, especially at low ...redshifts (z< 1.5) LGRBs seem to prefer particular types of environment. Our aim is to study the host galaxies of a complete sample of bright LGRBs to investigate the effect of the environment on GRB formation. Methods. We studied host galaxy spectra of the Swift/BAT6 complete sample of 14 z< 1 bright LGRBs. We used the detected nebular emission lines to measure the dust extinction, star formation rate (SFR), and nebular metallicity (Z) of the hosts and supplemented the data set with previously measured stellar masses M sub(*). The distributions of the obtained properties and their interrelations (e.g. mass-metallicity and SFR-M sub(*) relations) are compared to samples of field star-forming galaxies. Results. We find that LGRB hosts at z< 1 have on average lower SFRs than if they were direct star formation tracers. By directly comparing metallicity distributions of LGRB hosts and star-forming galaxies, we find a good match between the two populations up to 12 +log (ProQuest: Formulae and/or non-USASCII text omitted) ~8.4-8.5, after which the paucity of metal-rich LGRB hosts becomes apparent. The LGRB host galaxies of our complete sample are consistent with the mass-metallicity relation at similar mean redshift and stellar masses. The cutoff against high metallicities (and high masses) can explain the low SFR values of LGRB hosts. We find a hint of an increased incidence of starburst galaxies in the Swift/BAT6 z< 1 sample with respect to that of a field star-forming population. Given that the SFRs are low on average, the latter is ascribed to low stellar masses. Nevertheless, the limits on the completeness and metallicity availability of current surveys, coupled with the limited number of LGRB host galaxies, prevents us from investigating more quantitatively whether the starburst incidence is such as expected after taking into account the high-metallicity aversion of LGRB host galaxies.
Magnetic hyperthermia is an oncological therapy where magnetic nanostructures, under a radiofrequency field, act as heat transducers increasing tumour temperature and killing cancerous cells. ...Nanostructure heating efficiency depends both on the field conditions and on the nanostructure properties and mobility inside the tumour. Such nanostructures are often incorrectly bench-marketed in the colloidal state and using field settings far off from the recommended therapeutic values. Here, we prepared nanoclusters composed of iron oxide magnetite nanoparticles crystallographically aligned and their specific absorption rate (SAR) values were calorimetrically determined in physiological fluids, agarose-gel-phantoms and ex vivo tumours extracted from mice challenged with B16-F0 melanoma cells. A portable, multipurpose applicator using medical field settings; 100 kHz and 9.3 kA m
, was developed and the results were fully analysed in terms of nanoclusters' structural and magnetic properties. A careful evaluation of the nanoclusters' heating capacity in the three milieus clearly indicates that the SAR values of fluid suspensions or agarose-gel-phantoms are not adequate to predict the real tissue temperature increase or the dosage needed to heat a tumour. Our results show that besides nanostructure mobility, perfusion and local thermoregulation, the nanostructure distribution inside the tumour plays a key role in effective heating. A suppression of the magnetic material effective heating efficiency appears in tumour tissue. In fact, dosage had to be increased considerably, from the SAR values predicted from fluid or agarose, to achieve the desired temperature increase. These results represent an important contribution towards the design of more efficient nanostructures and towards the clinical translation of hyperthermia.
Maltodextrin is commonly used as wall material for protection of bioactive compounds. This work explored the OSA modification of maltodextrin to improve the stability of microcapsules obtained by ...spray drying process. OSA maltodextrin showed a degree of substitution of 0.020 with OS groups by weight of about 2.49%. OSA maltodextrin exhibited improved emulsification capacity compared to its non-modified counterpart. The microencapsulation stability was tested with avocado essential oil, where the OSA maltodextrin presented the better conditions against adverse effects of storage conditions, as revealed by monitoring the peroxide index. OSA maltodextrin reduced by about 80% the oxidation of the essential oil as compared to its non-modified counterpart. Confocal microscopy images indicated that the improved stability of OSA microcapsules can be explained from the aggregation of particles and the reduced fraction of free oil, which avoided the exposure of the essential oil to oxidative factors.
We present a technique that permits the analysis of stellar population gradients in a relatively low-cost way compared to integral field unit (IFU) surveys. We developed a technique to analyze ...unresolved stellar populations of spatially resolved galaxies based on photometric multi-filter surveys. This technique allows the analysis of vastly larger samples and out to larger galactic radii. We derived spatially resolved stellar population properties and radial gradients by applying a centroidal Voronoi tessellation and performing a multicolor photometry spectral energy distribution fitting. This technique has been successfully applied to a sample of 29 massive (M⋆ > 1010.5M⊙) early-type galaxies at z < 0.3 from the ALHAMBRA survey. We produced detailed 2D maps of stellar population properties (age, metallicity, and extinction), which allow us to identify galactic features. Radial structures were studied, and luminosity-weighted and mass-weighted gradients were derived out to 2–3.5 Reff. We find that the spatially resolved stellar population mass, age, and metallicity are well represented by their integrated values. We find the gradients of early-type galaxies to be on average flat in age (∇log AgeL = 0.02 ± 0.06 dex/Reff) and negative in metallicity (∇Fe/HL = −0.09 ± 0.06 dex/Reff). Overall,the extinction gradients are flat (∇Av = −0.03 ± 0.09 mag/Reff ) with a wide spread. These results are in agreement with previous studies that used standard long-slit spectroscopy, and with the most recent IFU studies. According to recent simulations, these results are consistent with a scenario where early-type galaxies were formed through major mergers and where their final gradients are driven by the older ages and higher metallicity of the accreted systems. We demonstrate the scientific potential of multi-filter photometry to explore the spatially resolved stellar populations of local galaxies and confirm previous spectroscopic trends from a complementary technique.
Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are ...needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.
We present the Lyman-
α
(Ly
α
) luminosity function (LF) at 2.05 <
z
< 3.75, estimated from a sample of 67 Ly
α
-emitter (LAE) candidates in the Javalambre Physics of the Accelerating Universe ...Astronomical Survey (J-PAS) pathfinder surveys: miniJPAS and J-NEP. These two surveys cover a total effective area of ∼1.14 deg
2
with 54 narrow band (NB) filters (
FWHM
∼ 145 Å) across the optical range, with typical limiting magnitudes of ∼23. This set of NBs allowed us to probe Ly
α
emission in a wide and continuous range of redshifts. We developed a method for detecting Ly
α
emission for the estimation of the Ly
α
LF using the whole J-PAS filter set. We tested this method by applying it to the miniJPAS and J-NEP data. In order to compute the corrections needed to estimate the Ly
α
LF and to test the performance of the candidate selection method, we built mock catalogs. These include representative populations of LAEs at 1.9 <
z
< 4.5 as well as their expected contaminants, namely low-
z
galaxies and
z
< 2 quasi-stellar objects (QSOs). We show that our method is able to provide the Ly
α
LF at the intermediate-bright range of luminosity (43.5 ≲ log
10
(
L
Ly
α
/erg s
−1
) ≲ 44.5) combining both miniJPAS and J-NEP. The photometric information provided by these surveys suggests that our samples are dominated by bright, Ly
α
-emitting active galactic nuclei (i.e., AGNs). At log
10
(
L
Ly
α
/erg s
−1
) < 44.5, we fit our Ly
α
LF to a power law with a slope of
A
= 0.70 ± 0.25. We also fit a Schechter function to our data, obtaining the following: log
10
(Φ
∗
/Mpc
−3
) = −6.30
−0.70
+0.48
, log
10
(
L
∗
/erg s
−1
) = 44.85
−0.32
+0.50
, and
α
= −1.65
−0.27
+0.29
. Overall, our results confirm the presence of an AGN component at the bright end of the Ly
α
LF. In particular, we find no significant contribution of star-forming LAEs to the Ly
α
LF at log
10
(
L
Ly
α
/erg s
−1
) > 43.5. This work serves as a proof of concept for the results that can be obtained with the upcoming data releases of the J-PAS survey.
This study reports the impact of examining either with digital or paper-based tests in science subjects taught across the secondary level. With our method, we compare the percentile ranking scores of ...two cohorts earned in computer- and paper-based teacher-made assessments to find signals of a testing mode effect. It was found that overall, at cohort and gender levels, pupils were rank-ordered equivalently in both testing modes. Furthermore, females and top-achieving pupils were the two subgroups where the differences between modes were smaller. The practical implications of these findings are discussed from the lens of a case study and the doubt about whether regular schools could afford to deliver high-stakes computer-based tests.
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