852 research outputs found
Gas-phase formation of glycolonitrile in the interstellar medium
Our automated reaction discovery program, AutoMeKin, has been utilized to
investigate the formation of glycolonitrile (HOCHCN) in the gas phase
under the low temperatures of the interstellar medium (ISM). The feasibility of
a proposed pathway depends on the absence of barriers above the energy of
reactants and the availability of the suggested precursors in the ISM. Based on
these criteria, several radical-radical reactions and a radical-molecule
reaction have been identified as viable formation routes in the ISM. Among the
radical-radical reactions, OH+CHCN appears to be the most relevant,
considering the energy of the radicals and its ability to produce
glycolonitrile in a single step. However, our analysis reveals that this
reaction produces hydrogen isocyanide (HNC) and formaldehyde (CHO), with
rate coefficients ranging from (7.3-11.5)10 cm
molecule s across the temperature range of 10-150 K. This finding
is particularly interesing given the persistently unexplained overabundance of
hydrogen isocyanide in the ISM. Among the radical-molecule reactions
investigated, the most promising one is OH+CHCNH, which forms
glycolonitrile and atomic hydrogen with rate coefficients in the range
(0.3-6.6)10 cm molecule s within the 10-150 K
temperature range. Our calculations indicate that the formation of both
hydrogen isocyanide and glycolonitrile is efficient under the harsh conditions
of the ISM
3D numerical simulation of slope-flexible system interaction using a mixed FEM-SPH model
Flexible membranes are light structures anchored to the ground that protect infrastructures or dwellings from rock or soil sliding. One alternative to design these structures is by using numerical simulations. However, very few models were found until date and most of them are in 2D and do not include all their components. This paper presents the development of a numerical model combining Finite Element Modelling (FEM) with Smooth Particle Hydrodynamics (SPH) formulation. Both cylindrical and spherical failure of the slope were simulated. One reference geometry of the slope was designed and a total of 21 slip circles were calculated considering different soil parameters, phreatic level position and drainage solutions. Four case studies were extracted from these scenarios and simulated using different dimensions of the components of the system. As a validation model, an experimental test that imitates the soil detachment and its retention by the steel membrane was successfully reproduced.The FORESEE project has received funding from the EuropeanUnion’s Horizon 2020 research and innovation program undergrant agreement No 769373
Realización de un proyecto en grupo con carácter multidisciplinar para alumnos de Ingeniería de la Salud usando la metodología ABP
La sociedad avanza, y este avance favorece la
aparición de nuevas necesidades, las cuales son
cubiertas por profesionales especializados en campos
específicos, como médicos, ingenieros, profesores,
etc. Pero cada vez más, estos nuevos “problemas”
requieren soluciones complejas y multidisciplinares,
haciendo uso de varios campos de conocimiento. Es
por esto que, en los últimos años, se hayan creado
nuevas titulaciones en el ámbito universitario para
formar a profesionales que posean los conocimientos
necesarios para afrontar estos nuevos retos. Este es el
caso del grado en Ingeniería de la Salud, el cual tiene
un carácter multidisciplinar, combinando
conocimientos biomédicos aplicados a la ingeniería
informática e ingeniería en general.
Los alumnos que eligen esta titulación se pueden
catalogar en dos perfiles diferenciados: los
procedentes de la rama científica-tecnológica y los de
ciencias de la salud del bachillerato. Dado que las
asignaturas de la titulación en los primeros años son
de formación básica y se dividen prácticamente en
50% de una rama y 50% de la otra, según la
procedencia del alumno puede que encuentre mayor
dificultad en las asignaturas que no son de la suya en
concreto.
En el curso académico 14/15, propusimos la
realización de un proyecto en grupo cuyos integrantes
estaban combinados entre alumnos de la rama
científica-tecnológica y de la salud, y cuyo tema
requería conocimientos de ambos campos, de forma
que hubiera una colaboración entre ambas partes. La
finalidad de este proyecto era que los alumnos
asimilaran los conceptos teóricos que eran nuevos
para ellos aplicándolos a una situación real
apoyándose en el resto de los miembros del grupo. El
proyecto se desarrolló siguiendo la metodología de
aprendizaje ABP aplicada en las sesiones prácticas de la asignatura, marcándose en cada una de estas
sesiones una serie de hitos que los alumnos deberán ir
completando. Se midió el grado de satisfacción de los
alumnos mediante un cuestionario, obteniendo como
resultado un alto grado de satisfacción.Society progresses very quickly, and that progress
favors the emergence of new needs. These needs are
provided, mostly, by experts in specific fields, such as
doctors, engineers, teachers, etc. But increasingly,
these new "problems" require complex and
multidisciplinary solutions, involving different fields
of knowledge. This is the main reason why, in recent
years, new degrees have appeared, educating future
experts in these fields to be able to face these new
challenges. This is the case of Health Engineering
Degree, which has multidisciplinary contents,
combining biomedical knowledge applied to
computer science and engineering.
The students in this degree can be differentiated
into two different categories, depending the high
school studies selection: those from the scientifictechnological
area and those from the health science
area. Since the subjects of the first course of this
degree are divided almost 50% from one area and
50% of the other, according to previous studies, the
student may find more difficulty in subjects that are
not in the their knowledge field.
In the academic year 14/15, the development of a
project in working groups whose members were
combined between students of scientifictechnological
education and students of health
science was proposed. This work required knowledge
of both fields, so they had to collaborate. The purpose
of this project was that the students assimilated the
theoretical concepts that were new to them applying
the new concepts to a real situation supporting on the rest of the group. The project was development
following the learning methodology PBL (Problembased
learning) applied in practical sessions with
milestones that students must complete. Both the
satisfaction and motivation of the students were
measured by a questionnaire, obtaining very good
results, meaning that the students enjoyed
collaborating with other teammates to face a
multidisciplinary project
3D numerical simulation of slope-flexible system interaction using a mixed FEM-SPH model
Flexible membranes are light structures anchored to the ground that protect infrastructures or dwellings from rock or soil sliding. One alternative to design these structures is by using numerical simulations. However, very few models were found until date and most of them are in 2D and do not include all their components. This paper presents the development of a numerical model combining Finite Element Modelling (FEM) with Smooth Particle Hydrodynamics (SPH) formulation. Both cylindrical and spherical failure of the slope were simulated. One reference geometry of the slope was designed and a total of 21 slip circles were calculated considering different soil parameters, phreatic level position and drainage solutions. Four case studies were extracted from these scenarios and simulated using different dimensions of the components of the system. As a validation model, an experimental test that imitates the soil detachment and its retention by the steel membrane was successfully reproduced
Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer
Biomarcadores del cáncer; Cáncer metástico colorrectal; Terapias experimentalesCancer biomarkers; Colorectal metastatic cancer; Experimental therapiesBiomarcadors del càncer; Càncer metastàtic colorrectal; Teràpies experimentalsProtein biomarkers are widely used in cancer diagnosis, prognosis, and prediction of treatment response. Here we introduce the use of targeted multiplex proteomics (TMP) as a tool to simultaneously measure a panel of 54 proteins involved in oncogenic, tumour suppression, drug metabolism and resistance, in patients with metastatic colorectal cancer (mCRC). TMP provided valuable diagnostic information by unmasking an occult neuroendocrine differentiation and identifying a misclassified case based on abnormal proteins phenotype. No significant differences in protein levels between unpaired primary and metastatic samples were observed. Four proteins were found differentially expressed in KRAS-mutant as compared to wild-type tumours (overexpressed in mutant: KRAS, EGFR; overexpressed in wild-type: TOPO1, TOP2A). Survival analyses revealed the association between mesothelin expression and poor overall survival, whereas lack of PTEN protein expression associated with lower progression-free survival with anti-EGFR-based therapy in the first-line setting for patients with RAS wild-type tumour. Finally, outlier analysis identified putative targetable proteins in 65% of patients lacking a targetable genomic alteration. Our data show that TMP constitutes a promising, novel molecular prescreening tool in mCRC to identify protein expression alterations that may impact on patient outcomes and more precisely guide patient eligibility to clinical trials with novel targeted experimental therapies
Luminescent Au(III)−M(I) (M = Cu, Ag) aggregates based on dicyclometalated bis(alkynyl) gold anions
The syntheses and structures of a series of complexes based on the C^C-chelated Au(III) unit (C^C = 4,4′-bis(t-butyl) 2,2′-biphenyl-1,1′-diyl) are reported, namely [{(C^C)Au(C≡CtBu)2}2M2], (C^C)Au(C≡CR)(C≡NXyl), ) and [{(C^C)Au(C≡CR)2}{M(C≡NXyl)}] (M = Ag, Cu; R = tBu, C6H4tBu-4, C6H4OMe-4; Xyl = 3,5-Me2C6H3). The X-ray structures reveal a broad range of dispositions determined by the different coordination modes of Ag(I) or Cu(I) in the different structures. The complexes are bright photoemitters in the solid state and in poly(methyl methacrylate) (PMMA) films. The photoluminescence is dominated by 3IL(C^C) transitions, with indirect effects from the rest of the molecules, as supported by theoretical calculations. This work opens up the possibility of accessing Au(III) carbon rich anions to construct photoluminescent aggregates
Current professional standing of young medical oncologists in Spain : a nationwide survey by the Spanish Society of Medical Oncology + MIR section
There is a lack of knowledge about the career paths and employment situation of young medical oncologists. The aim of our study was to evaluate the current professional standing of these professionals in Spain. The Spanish Society of Medical Oncology + MIR section conducted a national online survey in May 2021 of young medical oncology consultants (< 6 years of expertise) and final year medical oncology residents. A total of 162 responses were eligible for analysis and included participants from 16 autonomous communities; 64% were women, 80% were consultants, and 20% were residents. More than half of the participants performed routine healthcare activity and only 7% research activity. Almost three quarters (73%) were subspecialized in a main area of interest and almost half of these chose this area because it was the only option available after residency. Half of the respondents (51%) considered working abroad and 81% believed the professional standing in Spain was worse than in other countries. After finishing their residency, only 22 were offered a job at their training hospital. Just 16% of participants had a permanent employment contract and 87% were concerned (score of ≥ 5 on a scale of 1-10) about their job stability. In addition, one quarter of the participants in our study showed an interest in increasing their research activity. The choice of subspecialty in medical oncology may depend on job opportunities after residency rather than personal interest. The abundance of temporary contracts may have influenced the job stability concerns observed. Future mentoring strategies should engage in building a long-term career path for young medical oncologists. The online version contains supplementary material available at 10.1007/s12094-022-02989-3
Dynamic Edematous Response of the Human Heart to Myocardial Infarction Implications for Assessing Myocardial Area at Risk and Salvage
BACKGROUND: Clinical protocols aimed to characterize the post-myocardial
infarction (MI) heart by cardiac magnetic resonance (CMR) need to be
standardized to take account of dynamic biological phenomena evolving
early after the index ischemic event. Here, we evaluated the time course
of edema reaction in patients with ST-segment-elevation MI by CMR and
assessed its implications for myocardium-at-risk (MaR) quantification
both in patients and in a large-animal model.
METHODS: A total of 16 patients with anterior ST-segment-elevation MI
successfully treated by primary angioplasty and 16 matched controls were
prospectively recruited. In total, 94 clinical CMR examinations were
performed: patients with ST-segment-elevation MI were serially scanned
(within the first 3 hours after reperfusion and at 1, 4, 7, and 40
days), and controls were scanned only once. T2 relaxation time in the
myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau
triple inversion-recovery (ie, CMR-MaR) were evaluated at all time
points. In the experimental study, 20 pigs underwent 40-minute
ischemia/reperfusion followed by serial CMR examinations at 120 minutes
and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by
contrast-multidetector computed tomography during the index coronary
occlusion. Generalized linear mixed models were used to take account of
repeated measurements.
RESULTS: In humans, T2 relaxation time in the ischemic myocardium
declines significantly from early after reperfusion to 24 hours, and
then increases up to day 4, reaching a plateau from which it decreases
from day 7. Consequently, edema extent measured by T2-weighted short-tau
triple inversion-recovery (CMR-MaR) varied with the timing of the CMR
examination. These findings were confirmed in the experimental model by
showing that only CMR-MaR values for day 4 and day 7 postreperfusion,
coinciding with the deferred edema wave, were similar to values measured
by reference contrast-multidetector computed tomography.
CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that
affects CMR estimates of MaR. Dynamic changes in
post-ST-segment-elevation MI edema highlight the need for
standardization of CMR timing to retrospectively delineate MaR and
quantify myocardial salvage. According to the present clinical and
experimental data, a time window between days 4 and 7 post-MI seems a
good compromise solution for standardization. Further studies are needed
to study the effect of other factors on these variables.This study was partially supported by a competitive grant from the
Spanish Society of Cardiology (Proyectos de Investigacion Traslacional
en Cardiologia de la Sociedad Espanola de Cardiologia 2015, for the
project Caracterizacion tiSUlar miocaRdica con resonancia magnetica en
pacientes tras inFarto agudo de mioCardio con elevacioN de ST sometidos
a angloplastia Coronaria primaria. Estudio SURF-CNIC), by a competitive
grant from the Carlos III Institute of Health-Fondo de Investigacion
Sanitaria- and the European Regional Development Fund (ERDF/FEDER)
(PI10/02268 and PI13/01979), the Spanish Ministry of economy, industry,
and competitiveness (MEIC) and ERDF/FEDER SAF2013-49663-EXP. Dr
Fernandez-Jimenez holds a FICNIC fellowship from the Fundacio Jesus
Serra, the Fundacion Interhospitalaria de Investigacion Cardiovascular,
and the Centro Nacional de Investigaciones Cardiovasculares Carlos III
(CNIC), and Dr Aguero is a FP7-PEOPLE-2013-ITN-Cardionext fellow. This
study forms part of a Master Research Agreement between the CNIC and
Philips Healthcare, and is part of a bilateral research program between
Hospital de Salamanca Cardiology Department and the CNIC. This research
program is part of an institutional agreement between FIIS-Fundacion
Jimenez Diaz and CNIC. The CNIC is supported by the MEIC and the Pro
CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award
SEV-2015-0505).S
West Nile virus emergence in humans in Extremadura, Spain 2020
In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.This research was partially funded by the project PI19CIII/00014 from the Instituto de Salud Carlos III.S
Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation
Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant number COV20/1144 (MPY224/20) to AF-R/MJ-S). The study was also funded by CIBER - Consorcio Centro de Investigación Biomédica en Red - (CB 2021; CB21/13/00044), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - NextGenerationEU. AF-R and MJ-S are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MJ-S). Universidad Alfonso X el Sabio, grant number 1.013.005S
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