79 research outputs found
Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide
Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ? 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ? 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD
First record of the freshwater copepod Eucyclops titicacae Kiefer, 1957, new rank (Copepoda, Cyclopoida) in Colombia
Nutrición enteral domiciliaria en España: registro Nadya del año 2011-2012
Objective: To describe the results of the home enteral
nutrition (HEN) registry of the NADYA-SENPE group in
2011 and 2012.
Material and methods: We retrieved the data of the patients
recorded from January 1st 2011 to December 31st 2012.
Results: There were 3021 patients in the registry
during the period from 29 hospitals, which gives 65.39 per
million inhabitants. 97.95% were adults, 51.4% male.
Mean age was 67.64 ± 19.1, median age was 72 years for
adults and 7 months for children. Median duration with
HEN was 351 days and for 97.5% was their first event
with HEN. Most patients had HEN because of neurological
disease (57.8%). Access route was nasogastric tube
for 43.5% and gastrostomy for 33.5%. Most patients had
limited activity level and, concerning autonomy, 54.8%
needed total help. Nutritional formula was supplied from
chemist’s office to 73.8% of patients and disposables,
when necessary, was supplied from hospitals to 53.8% of
patients. HEN was finished for 1,031 patients (34.1%)
during the period of study, 56.6% due to decease and
22.2% due to recovery of oral intake.
Conclusions: Data from NADYA-SENPE registry
must be explained cautiously because it is a non-compulsory
registry. In spite of the change in the methodology of
the registry in 2010, tendencies regarding HEN have been
maintained, other than oral routeObjetivos: Describir los resultados del registro de nutrición
enteral domiciliaria (NED) del grupo NADYASENPE
de los años 2011 y 12.
Material y métodos: Se recopilaron los datos introducidos
en el registro desde el 1 de enero de 2011 al 31 de diciembre
de 2012.
Resultados: Hubo 3021 pacientes en el registro durante
el periodo, procedentes de 29 hospitales, lo que da una
prevalencia de 65,39 casos por millón de habitantes.
97.95% fueron adultos, 51,4% varones. La edad media
fue 67,64 ± 19,1 años y la mediana 72 años para los adultos
y 7 meses para los niños. La duración media de la NED
fue 351 días y para el 97,5% fue el primer episodio con
NED. La mayoría de pacientes tenían NED por una enfermedad
neurológica (57,8%). La vía de acceso fue sonda
nasogástrica para el 43,5% y gastrostomía para el 33,5%.
La mayoría de pacientes tuvieron un nivel de actividad física
limitado y, respecto a la autonomía, 54,8% necesitaba
ayuda total. La fórmula de nutrición se suministró desde
las oficinas de farmacia para el 73,8% y los fungibles,
cuando fueron necesarios, desde los hospitales para el
53,8%. La NED se suspendió en 1.031 pacientes (34,1%)
durante el periodo de estudio, 56,6% debido a fallecimiento
y 22,2% debido a recuperación de la vía oral.
Conclusiones: Los datos del registro NADYA-SENPE
deben ser interpretados con precaución ya que se trata de
un registro voluntario. A pesar del cambio de metodología
del registro en 2010, las tendencias en NED se han mantenido,
salvo la importancia cuantitativa de la vía ora
The CARMENES search for exoplanets around M dwarfs. Two temperate Earth-mass planet candidates around Teegarden’s Star
Context.Teegarden’s Star is the brightest and one of the nearest ultra-cool dwarfs in the solar neighbourhood. For its late spectral type (M7.0 V),the star shows relatively little activity and is a prime target for near-infrared radial velocity surveys such as CARMENES.Aims.As part of the CARMENES search for exoplanets around M dwarfs, we obtained more than 200 radial-velocity measurements of Teegarden’sStar and analysed them for planetary signals.Methods.We find periodic variability in the radial velocities of Teegarden’s Star. We also studied photometric measurements to rule out stellarbrightness variations mimicking planetary signals.Results.We find evidence for two planet candidates, each with 1.1M⊕minimum mass, orbiting at periods of 4.91 and 11.4 d, respectively. Noevidence for planetary transits could be found in archival and follow-up photometry. Small photometric variability is suggestive of slow rotationand old age.Conclusions.The two planets are among the lowest-mass planets discovered so far, and they are the first Earth-mass planets around an ultra-cooldwarf for which the masses have been determined using radial velocities.We thank the referee Rodrigo Díaz for a careful review andhelpful comments. M.Z. acknowledges support from the Deutsche Forschungs-gemeinschaft under DFG RE 1664/12-1 and Research Unit FOR2544 “BluePlanets around Red Stars”, project no. RE 1664/14-1. CARMENES isan instrument for the Centro Astronómico Hispano-Alemán de Calar Alto(CAHA, Almería, Spain). CARMENES is funded by the German Max-Planck-Gesellschaft (MPG), the Spanish Consejo Superior de InvestigacionesCientíficas (CSIC), the European Union through FEDER/ERF FICTS-2011-02 funds, and the members of the CARMENES Consortium (Max-Planck-Institut für Astronomie, Instituto de Astrofísica de Andalucía, LandessternwarteKönigstuhl, Institut de Ciències de l’Espai, Institut für Astrophysik Göttingen,Universidad Complutense de Madrid, Thüringer Landessternwarte Tautenburg,Instituto de Astrofísica de Canarias, Hamburger Sternwarte, Centro de Astro-biología and Centro Astronómico Hispano-Alemán), with additional contribu-tions by the Spanish Ministry of Economy, the German Science Foundationthrough the Major Research Instrumentation Programme and DFG ResearchUnit FOR2544 “Blue Planets around Red Stars”, the Klaus Tschira Stiftung, thestates of Baden-Württemberg and Niedersachsen, and by the Junta de Andalucía.Based on data from the CARMENES data archive at CAB (INTA-CSIC). Thisarticle is based on observations made with the MuSCAT2 instrument, devel-oped by ABC, at Telescopio Carlos Sánchez operated on the island of Tener-ife by the IAC in the Spanish Observatorio del Teide. Data were partly col-lected with the 150-cm and 90-cm telescopes at the Sierra Nevada Observa-tory (SNO) operated by the Instituto de Astrofísica de Andalucía (IAA-CSIC).Data were partly obtained with the MONET/South telescope of the MOnitoringNEtwork of Telescopes, funded by the Alfried Krupp von Bohlen und HalbachFoundation, Essen, and operated by the Georg-August-Universität Göttingen,the McDonald Observatory of the University of Texas at Austin, and the SouthAfrican Astronomical Observatory. We acknowledge financial support from theSpanish Agencia Estatal de Investigación of the Ministerio de Ciencia, Inno-vación y Universidades and the European FEDER/ERF funds through projectsAYA2015-69350-C3-2-P, AYA2016-79425-C3-1/2/3-P, AYA2018-84089, BES-2017-080769, BES-2017-082610, ESP2015-65712-C5-5-R, ESP2016-80435-C2-1/2-R, ESP2017-87143-R, ESP2017-87676-2-2, ESP2017-87676-C5-1/2/5-R, FPU15/01476, RYC-2012-09913, the Centre of Excellence ”Severo Ochoa”and ”María de Maeztu” awards to the Instituto de Astrofísica de Canarias (SEV-2015-0548), Instituto de Astrofísica de Andalucía (SEV-2017-0709), and Cen-tro de Astrobiología (MDM-2017-0737), the Generalitat de Catalunya throughCERCA programme”, the Deutsches Zentrum für Luft- und Raumfahrt throughgrants 50OW0204 and 50OO1501, the European Research Council through grant694513, the Italian Ministero dell’instruzione, dell’università de della ricerca andUniversità degli Studi di Roma Tor Vergata through FFABR 2017 and “Mis-sion: Sustainability 2016”, the UK Science and Technology Facilities Council through grant ST/P000592/1, the Israel Science Foundation through grant848/16, the Chilean CONICYT-FONDECYT through grant 3180405, the Mexi-can CONACYT through grant CVU 448248, the JSPS KAKENHI through grantsJP18H01265 and 18H05439, and the JST PRESTO through grant JPMJPR1775
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2
The CARMENES search for exoplanets around M dwarfs HD147379 b: A nearby Neptune in the temperate zone of an early-M dwarf
We report on the first star discovered to host a planet detected by radial velocity (RV) observations obtained within the CARMENES survey for exoplanets around M dwarfs. HD 147379 (V = 8.9 mag, M = 0.58 ± 0.08 M⊙), a bright M0.0 V star at a distance of 10.7 pc, is found to undergo periodic RV variations with a semi-amplitude of K = 5.1 ± 0.4 m s−1 and a period of P = 86.54 ± 0.06 d. The RV signal is found in our CARMENES data, which were taken between 2016 and 2017, and is supported by HIRES/Keck observations that were obtained since 2000. The RV variations are interpreted as resulting from a planet of minimum mass mP sin i = 25 ± 2 M⊕, 1.5 times the mass of Neptune, with an orbital semi-major axis a = 0.32 au and low eccentricity (e < 0.13). HD 147379 b is orbiting inside the temperate zone around the star, where water could exist in liquid form. The RV time-series and various spectroscopic indicators show additional hints of variations at an approximate period of 21.1 d (and its first harmonic), which we attribute to the rotation period of the star.FEDER/ERF FICTS-2011-02 fundsMajor Research Instrumentation Programme
and DFG Research Unit FOR2544 “Blue Planets around Red StarsEuropean Research Council (ERC-279347), Deutsche Forschungsgemeinschaft
(RE 1664/12-1, RE 2694/4-1), Bundesministerium für Bildung
und Forschung (BMBF-05A14MG3, BMBF-05A17MG3), Spanish Ministry
of Economy and Competitiveness (MINECO, grants AYA2015-68012-C2-2-P,
AYA2016-79425-C3-1,2,3-P, AYA2015-69350-C3-2-P, AYA2014-54348-C03-
01, AYA2014-56359-P, AYA2014-54348-C3-2-R, AYA2016-79425-C3-3-P and
2013 Ramòn y Cajal program RYC-2013-14875), Fondo Europeo de Desarrollo
Regional (FEDER, grant ESP2016-80435-C2-1-R, ESP2015-65712-C5-
5-R), Generalitat de Catalunya/CERCA programme, Spanish Ministerio de
Educación, Cultura y Deporte, programa de Formación de Profesorado Universitario
(grant FPU15/01476), Deutsches Zentrum für Luft- und Raumfahrt
(grants 50OW0204 and 50OO1501), Office of Naval Research Global (award
no. N62909-15-1-2011), Mexican CONACyT grant CB-2012-183007
The hyporheic zone and its functions: revision and research status in Neotropical regions
Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens
Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children
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