Abstract
Background
Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative ...strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy.
Methods
In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia).
Results
A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome.
Conclusions
Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.
Clinical Trials Registration
NCT03123627.
In cytomegalovirus (CMV)-seropositive kidney transplant recipients receiving ATG induction, immunoguided prevention is not inferior to prophylaxis to prevent CMV complications. Prophylaxis can be prematurely discontinued after CMV–cell-mediated immunity recovery with no significant increase in the incidence of CMV replication or disease.
Context.
The morphology of galaxies provide us with a unique tool for relating and understanding other physical properties and their changes over the course of cosmic time. It is only recently that ...we have been afforded access to a wealth of data for an unprecedented number galaxies thanks to large and deep surveys.
Aims.
We present the morphological catalogue of the OTELO survey galaxies detected with the
Hubble
Space Telescope (HST)-ACS
F
814
W
images. We explore various methods applied in previous works to separate early-type (ET) and late-type (LT) galaxies classified via spectral energy distribution (SED) fittings using galaxy templates. Together with this article, we are releasing a catalogue containing the main morphological parameters in the
F
606
W
and
F
814
W
bands derived for more than 8000 sources.
Methods.
The morphological analysis is based on the single-Sérsic profile fit. We used the
GALAPAGOS2
software to provide multi-wavelength morphological parameters fitted simultaneously in two HST-ACS bands. The
GALAPAGOS2
software detects, prepares guess values for
GALFIT-M
, and provides the best-fitting single-Sérsic model in both bands for each source. Stellar masses were estimated using synthetic rest-frame magnitudes recovered from SED fittings of galaxy templates. The morphological catalogue is complemented with concentration indexes from a separate
SExtractor
dual, high dynamical range mode.
Results.
A total of 8812 sources were successfully fitted with single-Sérsic profiles. The analysis of a carefully selected sample of ∼3000 sources up to
z
phot
= 2 is presented in this work, of which 873 sources were not detected in previous studies. We found no statistical evidence for the evolution of the low-mass end of mass–size relation for ET and LT since
z
= 2. Furthermore, we found a good agreement for the median size evolution for ET and LT galaxies, for a given stellar mass, with the data from the literature. Compared to previous works on faint field galaxies, we found similarities regarding their rest-frame colours as well as the Sérsic and concentration indices.
Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL). The Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are important mediators of ...cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs) and pharmacologically (mainly with the pan-PIM inhibitor (PIMi) ETP-39010) in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL) cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.
Context. The morphology of galaxies provide us with a unique tool for relating and understanding other physical properties and their changes over the course of cosmic time. It is only recently that ...we have been afforded access to a wealth of data for an unprecedented number galaxies thanks to large and deep surveys. Aims. We present the morphological catalogue of the OTELO survey galaxies detected with the Hubble Space Telescope (HST)-ACS F814W images. We explore various methods applied in previous works to separate early-type (ET) and late-type (LT) galaxies classified via spectral energy distribution (SED) fittings using galaxy templates. Together with this article, we are releasing a catalogue containing the main morphological parameters in the F606W and F814W bands derived for more than 8000 sources. Methods. The morphological analysis is based on the single-Sérsic profile fit. We used the GALAPAGOS2 software to provide multi-wavelength morphological parameters fitted simultaneously in two HST-ACS bands. The GALAPAGOS2 software detects, prepares guess values for GALFIT-M, and provides the best-fitting single-Sérsic model in both bands for each source. Stellar masses were estimated using synthetic rest-frame magnitudes recovered from SED fittings of galaxy templates. The morphological catalogue is complemented with concentration indexes from a separate SExtractor dual, high dynamical range mode. Results. A total of 8812 sources were successfully fitted with single-Sérsic profiles. The analysis of a carefully selected sample of ∼3000 sources up to zphot = 2 is presented in this work, of which 873 sources were not detected in previous studies. We found no statistical evidence for the evolution of the low-mass end of mass–size relation for ET and LT since z = 2. Furthermore, we found a good agreement for the median size evolution for ET and LT galaxies, for a given stellar mass, with the data from the literature. Compared to previous works on faint field galaxies, we found similarities regarding their rest-frame colours as well as the Sérsic and concentration indices.
Purpose: Despite major advances in the treatment of classic Hodgkin's lymphoma (cHL), â¼30% of patients in advanced stages may eventually
die as result of the disease, and current methods to predict ...prognosis are rather unreliable. Thus, the application of robust
techniques for the identification of biomarkers associated with treatment response is essential if new predictive tools are
to be developed.
Experimental Design: We used gene expression data from advanced cHL patients to identify transcriptional patterns from the tumoral cells and their
nonneoplastic microenvironment, associated with lack of maintained treatment response. Gene-Set Enrichment Analysis was used
to identify functional pathways associated with unfavorable outcome that were significantly enriched in either the Hodgkin's
and Reed-Sternberg cells (regulation of the G 2 -M checkpoint, chaperones, histone modification, and signaling pathways) or the reactive cell microenvironment (mainly represented
by specific T-cell populations and macrophage activation markers).
Results: To explore the pathways identified previously, we used a series of 52 formalin-fixed paraffin-embedded advanced cHL samples
and designed a real-time PCR-based low-density array that included the most relevant genes. A large majority of the samples
(82.7%) and all selected genes were analyzed successfully with this approach.
Conclusions: The results of this assay can be combined in a single risk score integrating these biological pathways associated with treatment
response and eventually used in a larger series to develop a new molecular outcome predictor for advanced cHL.
La educación para los estudiantes sordos está en un proceso continuo de revisión, la inclusión de este grupo minoritario es una realidad y un desafío en las aulas de clases. Este articulo tiene como ...objetivo caracterizar los procesos cognitivos en el aula de clases de estudiantes sordos colombianos y chilenos de educación básica/primaria. Esta es una investigación con enfoque cualitativo, con diseño de estudio de casos múltiples. Los participantes fueron organizados en términos de aulas inclusivas chilenas (sordos y oyentes) y exclusivas colombianas (solo estudiantes sordos) de los niveles 3º, 4º y 5º año. Se aplicó la Pauta de Observación de Procesos Cognitivos (POPC), la que se organiza en 4 dimensiones: Procesos Cognitivos, Procesos Metacognitivos, Aspectos Motivacionales y Actividades suplementarias. Además, se aplicó una entrevista semiestructurada a los docentes, intérpretes de Lengua de Señas y coeducadores sordos. Los resultados se plantean en función de la descripción de las estrategias pedagógicas que usan los profesores sordos y oyentes para promover procesos cognitivos en el aula, considerando diferentes diadas (estudiante sordo-docente sordo/oyente, estudiante sordo-estudiante oyente, estudiante sordo-intérprete) Las conclusiones apuntan a que las aulas inclusiva favorecen el trabajo colaborativo y el aula exclusiva desarrolla estrategias en la lengua de señas potenciando los aprendizajes de los estudiantes sordos.
Although there is some evidence suggesting that olive oil could reduce breast cancer (BC) risk, the epidemiological data are still relatively limited, not entirely consistent and mainly based on ...case–control studies. Therefore, we prospectively assessed the association between olive oil and BC risk in postmenopausal women from the Mediterranean cohorts within the European Prospective Investigation into Cancer and Nutrition. The analysis included 62,284 postmenopausal women recruited from Spain, Italy and Greece who had complete dietary data (collected from validated country‐specific dietary questionnaires). The risk of BC (overall and by hormone receptor subtypes) was assessed using hazards ratios (HRs) obtained from Cox proportional hazards regression, while adjusting for known BC risk factors. After a mean follow‐up of 9 years, 1,256 women were diagnosed with a primary incident invasive BC. The multivariate HRs for BC risk by olive oil intake (highest vs. lowest tertile of g/day/2,000 kcal) were 1.07 (95% CI = 0.91–1.25) in the adjusted model, 1.06 (95% CI = 0.91–1.24) in the model additionally adjusted for reproductive‐related factors and 1.10 (95% CI = 0.92–1.31) for the model additionally adjusted for dietary factors. There was no association between olive oil and risk of estrogen or progesterone receptor‐positive tumors, but a suggestion of a negative association with estrogens and progesterone receptor‐negative tumors. The results from our prospective study showed that olive oil consumption during adult life was not associated with the risk of BC. However, larger prospective studies are still needed to explore possible differences related to hormone receptor status.
The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection. This need has generated a high number of new testing methods aimed at replacing RT-PCR, which ...is the golden standard for testing. Most of the testing techniques are based on biochemistry methods and require chemicals that are often expensive and the supply might become scarce in a large crisis. In the present paper we suggest the use of methods based on physics that leverage novel nanomaterials. We demonstrate that using Surface Enhanced Raman Spectroscopy (SERS) of virion particles a very distinct spectroscopic signature of the SARS-CoV-2 virus can be obtained. We demonstrate that the spectra are mainly composed by signals from the spike (S) and nucleocapsid (N) proteins. It is believed that a clinical test using SERS can be developed. The test will be fast, inexpensive, and reliable. It is also clear that SERS can be used for analysis of structural changes on the S and N proteins. This will be an example of application of nanotechnology and properties of nanoparticles for health and social related matters.
The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection.
The OTELO survey Bongiovanni, Ángel; Ramón-Pérez, Marina; Pérez García, Ana María ...
Astronomy and astrophysics (Berlin),
11/2019, Letnik:
631
Journal Article
Recenzirano
Odprti dostop
Context
. The evolution of galaxies through cosmic time is studied observationally by means of extragalactic surveys. The usefulness of these surveys is greatly improved by increasing the ...cosmological volume, in either depth or area, and by observing the same targets in different wavelength ranges. A multi-wavelength approach using different observational techniques can compensate for observational biases.
Aims
. The OTELO survey aims to provide the deepest narrow-band survey to date in terms of minimum detectable flux and emission line equivalent width in order to detect the faintest extragalactic emission line systems. In this way, OTELO data will complements other broad-band, narrow-band, and spectroscopic surveys.
Methods
. The red tunable filter of the OSIRIS instrument on the 10.4 m Gran Telescopio Canarias (GTC) is used to scan a spectral window centred at 9175 Å, which is free from strong sky emission lines, with a sampling interval of 6 Å and a bandwidth of 12 Å in the most deeply explored EGS region. Careful data reduction using improved techniques for sky ring subtraction, accurate astrometry, photometric calibration, and source extraction enables us to compile the OTELO catalogue. This catalogue is complemented with ancillary data ranging from deep X-ray to far-infrared, including high resolution HST images, which allow us to segregate the different types of targets, derive precise photometric redshifts, and obtain the morphological classification of the extragalactic objects detected.
Results
. The OTELO multi-wavelength catalogue contains 11 237 entries and is 50% complete at AB magnitude 26.38. Of these sources, 6600 have photometric redshifts with an uncertainty
δ
z
phot
better than 0.2 (1+
z
phot
). A total of 4336 of these sources correspond to preliminary emission line candidates, which are complemented by 81 candidate stars and 483 sources that qualify as absorption line systems. The OTELO survey results will be released to the public on the second half of 2019.
Abstract Background Encorafenib plus binimetinib (EB) is a standard of care treatment for advanced BRAFV600-mutant melanoma. We assessed efficacy and safety of encorafenib plus binimetinib in ...patients with BRAFV600-mutant melanoma and brain metastasis (BM) and explored if radiotherapy improves the duration of response. Methods E-BRAIN/GEM1802 was a prospective, multicenter, single arm, phase II trial that enrolled patients with melanoma BRAFV600-mutant and BM. Patients received encorafenib 450 mg once daily plus binimetinib 45 mg BID, and those who achieved partial response or stable disease at first tumor assessment were offered radiotherapy. Treatment continued until progression. Primary endpoint was intracranial response rate (icRR) after 2 months of EB, establishing a futility threshold of 60%. Results The study included 25 patients with no BM symptoms and 23 patients with BM symptoms regardless of using corticosteroids. Among them, 31 patients (64.6%) received sequential radiotherapy. After two months, icRR was 70.8% (95% CI: 55.9-83.1); 10.4% complete response. Median intracranial PFS and OS were 8.5 (95% CI: 6.4-11.8) and 15.9 (95% CI: 10.7-21.4) months, respectively (8.3 months for icPFS and 13.9 months OS for patients receiving RDT). Most common grade 3-4 treatment-related adverse event was alanine aminotransferase (ALT) increased (10.4%). Conclusion Encorafenib plus binimetinib showed promising clinical benefit in terms of icRR, and tolerable safety profile with low frequency of high grade TRAEs, in patients with BRAFV600-mutant melanoma and BM, including those with symptoms and need for steroids. Sequential radiotherapy is feasible but it does not seem to prolong response.
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