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PURPOSE: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. METHODS: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. RESULTS: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. CONCLUSION: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.

Unfortunately, there is a gap of understanding in the pathophysiology of chronic liver disease due to the lack of experimental models that exactly mimic the human disease. Additionally, the diagnosis of patients is very poor due to the lack of biomarkers than can detect the disease in early stages. Thus, it is of utmost interest the generation of a multidisciplinary consortium from different countries with a direct translation. The present reports the meeting of the 2021 Iberoamerican Consortium for the study of liver Cirrhosis, held online, in October 2021. The meeting, was focused on the recent advancements in the field of chronic liver disease and cirrhosis with a specific focus on cell pathobiology and liver regeneration, molecular and cellular targets involved in non-alcoholic hepatic steatohepatitis, alcoholic liver disease (ALD), both ALD and western diet, and end-stage liver cirrhosis and hepatocellular carcinoma. In addition, the meeting highlighted recent advances in targeted novel technology (-omics) and opening therapeutic avenues in this field of research.

The main objects of study in this article are pairs $(G, \mathcal{H})$ where $G$ is a topological group with a compact open subgroup, and $\mathcal{H}$ is a finite collection of open subgroups. We develop geometric techniques to study the notions of $G$ being compactly generated and compactly presented relative to $\mathcal H$. This includes topological characterizations in terms of discrete actions of $G$ on complexes, quasi-isometry invariance of certain graphs associated to the pairs $(G,\mathcal H)$ when $G$ is compactly generated relative to $\mathcal H$, and extensions of known results for the discrete case. For example, generalizing results of Osin for discrete groups, we show that in the case that $G$ is compactly presented relative to $\mathcal H$: $\bullet$ if $G$ is compactly generated, then each subgroup $H\in \mathcal H$ is compactly generated; $\bullet$ if each subgroup $H\in \mathcal H$ is compactly presented, then $G$ is compactly presented. The article also introduces an approach to relative hyperbolicity for pairs $(G, \mathcal H)$ based on Bowditch's work using discrete actions on hyperbolic fine graphs. For example, we prove that if $G$ is hyperbolic relative to $\mathcal H$ then $G$ is compactly presented relative to $\mathcal H$. As applications of the results of the article we prove combination results for coherent topological groups with a compact open subgroup, and extend McCammond-Wise perimeter method to this general framework., Version 4. Accepted in the Journal of Algebra

Resumen Introduccion La alimentacion oral de los recien nacidos pretermino (RNPT) esta dificultada por su inmadurez y enfermedades intercurrentes, lo que puede prolongar su estancia hospitalaria. El objetivo de este estudio fue valorar la efectividad de un programa que combina la estimulacion tactil, kinestesica y oral (ET + K + O) frente a otro de estimulacion oral sola (EO), en el tiempo necesario para lograr la alimentacion independiente y el alta hospitalaria. Pacientes y metodos Estudio clinico de 2 grupos aleatorizados (EO vs. ET + K + O), realizado en 42 RNPT con una edad gestacional entre 27-32 semanas y un peso al nacimiento > 900 g. Los programas de estimulacion fueron realizados en sesiones de 15 min, durante 10 dias. Resultados Los RNPT del grupo de ET + K + O consiguieron antes la alimentacion oral independiente, en comparacion con el grupo de EO (24,9 ± 10,1 vs. 34,1 ± 15,6 dias, p = 0,02). Se realizo un analisis de covarianza, observando que las covariables PN y EG tuvieron efectos significativos en el tiempo hasta alcanzar la alimentacion por succion (peso al nacimiento: F[1, 38] = 5,79; p = 0,021; edad gestacional: F[1, 38] = 14,12; p = 0,001) y que una vez controlado su efecto, la intervencion seguia teniendo un efecto significativo (F[1, 38] = 6,07; p = 0,018). El grupo de ET + K + O, en comparacion con el de EO, consiguio antes el alta hospitalaria (39 ± 15 vs. 45 ± 18 dias), si bien la diferencia no fue significativa (p = 0,21). Conclusiones Las terapias combinadas que asocian ET + K + O son mas eficaces que la EO sola, para lograr la alimentacion oral independiente en los RNPT.

This article describes the essential elements of research work directly related to quality processes within universities, taking the rationalist method as an essential method, to determine functional aspects that can be transformed within education systems in the world. It is proposed that operationally the economy-education relationship tends to be dysfunctional since complex administrative and educational models that correspond to the reality of teaching and learning within the university classroom have not been generated, assuming a critical but open position towards new ways of understanding the phenomenon and transforming it to improve quality within higher education institutions.

The Farrell technical efficiency measure computes the maximum proportional reduction that can be operated on inputs without affecting the level of output. In a multi-input and multi-output context, the first mathematical programming based reformulation of this problem is known as CCR/BCC efficiency measures. There are two drawbacks to this measure. First, it does not give value to any inefficiency resulting from the possibility of reducing some inputs and/or increasing some outputs in addition to the maximum proportional reduction in inputs. Second, as a result of the above, it does not unequivocally identify Pareto-Koopmans efficient activities. This article presents a strong efficiency measure similar to CCR/BCC models which overcome these drawbacks. It accounts for all non-zero slacks in inputs and outputs once the proportional reduction path in the inputs has been exhausted. This allows for the correct classification of production units in an efficiency ranking and facilitates the measurement of inefficiency by inputs and outputs, thereby helping to improve business management decision-making. We extend our model to deal with zero and negative input or output values. A numerical example shows the applicability of our approach.

Background Endothelial dysfunction is one of the underlying mechanisms to vascular and cardiac complications in patients with COVID-19. We sought to investigate the systemic vascular endothelial function and its temporal changes in COVID-19 patients from a non-invasive approach with reactive hyperemia peripheral arterial tonometry (PAT). Methods This is a prospective, observational, case-control and blinded study. The population was comprised by 3 groups: patients investigated during acute COVID-19 (group 1), patients investigated during past COVID-19 (group 2), and controls 1:1 matched to COVID-19 patients by demographics and cardiovascular risk factors (group 3). The natural logarithmic scaled reactive hyperemia index (LnRHI), a measure of endothelium-mediated dilation of peripheral arteries, was obtained in all the participants and compared between study groups. Results 144 participants were enrolled (72 COVID-19 patients and 72 matched controls). Median time from COVID-19 symptoms to PAT assessment was 9.5 and 101.5 days in groups 1 and 2, respectively. LnRHI was significantly lower in group 2 compared to both group 1 and controls (0.53 ± 0.23 group 2 vs. 0.72 ± 0.26 group 1, p = 0.0043; and 0.79 ± 0.23 in group 3, p Conclusions This study suggests a deleterious effect of SARS-CoV-2 infection on systemic vascular endothelial function. These findings open new venues to investigate the clinical implication and prognostic role of vascular endothelial dysfunction in COVID-19 patients and post-COVID syndrome using non-invasive techniques.

Current research on transparent conductive oxides deals with the development of environmentally friendly materials having competitive electrical and optical properties. Also, the synthesis methods need to be compatible with the state-of-the-art microelectronics and miniaturization. ZnO films doped with Al (AZO) via Atomic Layer Deposition (ALD) have been subjected to thorough investigation for the latter. However, the conventional doping schemes in ALD seem to have reached their limit and alternative approaches are currently being explored. This work contributes to the improvement of the Al-doping efficiency of ZnO by the ALD supercycle approach, applying the doping-cycle on nearly saturated ZnO surfaces. The electrical (ρ = 1.3 × 10−3 Ωcm, n = 3.79 × 1020 cm−3, and μ = 12.3 cm2/Vs) and optical (%T > 75) properties demonstrated typical values obtained by others applying the supercycle methodology. However, the main finding of this work is the trend observed in the electrical and optical properties, which suggests that the Al solubility limit was not reached as a result of the interaction between the dopant agent and the nearly saturated ZnO surfaces. This is also evidence that the dopant atoms do not become inactive once the compensation effect between substitutional doping and structural defects, has been established. These results open the possibility of exploring the incorporation of more Al into the ZnO structure following and optimizing the doping scheme used here, which at the same time, promises materials that could substitute indium-tin-oxide in many optoelectronic applications, attending the well-known environmental and economic issues.

Carbon surfaces become significantly activated with plasma treatment enhancing the surface energy, wettability, and bio-conjugation. However, the activated surfaces are influenced by aging effect or reorientation phenomenon, a rarely reported occurrence, that refers to the loss of surface activity with time. Generated plasma-activated surface functional groups suffer from a brief shelf life as they reorient themselves to occupy lower states of energy. This study thoroughly assesses plasma-treated pyrolyzed carbon platforms with O2, N2, and Ar plasma radiations over 3 weeks. Pristine, immediately treated, and aged carbon samples were analyzed by SEM, AFM, WCA, and XPS to observe physical and chemical changes of the surfaces. Moreover, the electrochemical analyses demonstrated radical alterations of the surface characteristics immediately after the treatment; an activation which did not last long regardless of the plasma choice. With time, clear signs of surface inactivation were recorded manifesting in the form of decreased roughness, increased water contact angle, and major alterations of surface chemical composition, capacitance, and resistance. Our observations confirm that the plasma-treated carbon samples return to the pristine surface characteristics within a brief period of time thus demonstrating the loss of surface activity irrespective of the treatment choice.

Control piles are devices that can address problems in buildings caused by the regional subsidence. This is done using a deformable cell that allows controlling the load applied on the pile head and the settlements of the structure. The most common cells are composed of arrangements of wooden cubes. The yield load on each cell is usually calculated based on the results of compression tests on individual cubes, which may lead to overestimations of the load. In this research, the mechanical behaviors of individual wooden cubes and sets of cubes are assessed with compression tests considering the effects of various factors, such as the volumetric weight of the cubes, the placement of galvanized steel sheets, the moisture in the cubes and the wood anisotropy. The understanding of the mechanical behavior of wooden cubes is very useful for the design of deformable cells and for the definition of criteria for the maintenance of this type of control device. The results of this research allow recommending a new criterion to estimate the yield load of deformable cells required for the appropriate design and functioning of control piles. In addition, a methodology to assess the mechanical behavior of deformable cells is proposed.

Traffic accidents are a major public health concern since they are the leading cause of death for those aged 15–29 years and the ninth cause of death worldwide. In this paper, we estimate the overall effect on traffic fatalities of the introduction of the Penalty Point System (PPS) in Spain in 2006, jointly with those of the publicity campaigns that went with it and the reform of the Penal Code to toughen the consequences of traffic offenses in 2007. We use a synthetic-control method that controls for differences in the distribution of control variables, changing business cycles conditions, the effect of unexpected policies or events that happen between the pre- and the post-PPS periods and the arbitrariness in the selection of the control group. We find that the introduction of the PPS and related initiatives lead to a reduction of almost 15% in traffic fatality rates in Spain during the first two years. The magnitude of the estimated effect monotonically increased over time until reaching a 40% reduction in fatality rates in 2009 and 2010.

Gallic (GA) and ellagic (EA) acids are present in foods, medicinal plants, teas, and dietary supplements. An acute toxicological study was conducted by oral administration of both compounds alone (200, 1000, and 2000 mg/kg) and combined (2000 mg/kg) and their effects on the electron transport chain (ETC) and the ROS production in kidney mitochondria further evaluated. All treatments induced a dose-dependent heart, lung, and kidney injury. However, the intensity of these effects varied according to the substance, with greater cardiac and renal toxicity for EA and pulmonary injury for GA, while the combination attenuated the toxicity of the isolated molecules. All substances inhibited the activity of complexes II, III, and IV of the ETC from renal mitochondria. However, no changes were observed regarding mitochondrial ROS production. These compounds have a non-negligible inherent deleterious potential, so their uncontrolled use at high doses (≥200 mg/kg) could cause undesirable effects.

Summary Background In hormone receptor-positive, HER2-negative early stage breast cancer, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy could represent an alternative to multiagent chemotherapy. We aimed to evaluate the biological and clinical activity of neoadjuvant ribociclib plus letrozole in the luminal B subtype of early stage breast cancer. Methods CORALLEEN is a parallel-arm, multicentre, randomised, open-label, phase 2 trial completed across 21 hospitals in Spain. We recruited postmenopausal women (≥18 years) with stage I–IIIA hormone receptor-positive, Eastern Cooperative Oncology Group Performance Status 0–1, HER2-negative breast cancer and luminal B by PAM50 with histologically confirmed, operable primary tumour size of at least 2 cm in diameter as measured by MRI. Patients were randomly assigned (1:1) using a web-based system and permuted blocks of 25 to receive either six 28-days cycles of ribociclib (oral 600 mg once daily for 3 weeks on, 1 week off) plus daily letrozole (oral 2·5 mg/day) or four cycles of doxorubicin (intravenous 60 mg/m2) and cyclophosphamide (intravenous 600 mg/m2) every 21 days followed by weekly paclitaxel (intravenous 80 mg/m2) for 12 weeks. The total duration of the neoadjuvant therapy was 24 weeks. Randomisation was stratified by tumour size and nodal involvement. Samples were prospectively collected at baseline (day 0), day 15, and surgery. The primary endpoint was to evaluate the proportion of patients with PAM50 low-risk-of-relapse (ROR) disease at surgery in the modified intention-to-treat population including all randomly assigned patients who received study drug and had a baseline and at least one post-baseline measurement of ROR score. The PAM50 ROR risk class integrated gene expression data, tumour size, and nodal status to define prognosis. This trial was registered at ClinicalTrials.gov , NCT03248427 . Findings Between July 27, 2017 to Dec 7, 2018, 106 patients were enrolled. At baseline, of the 106 patients, 92 (87%) patients had high ROR disease (44 [85%] of 52 in the ribociclib and letrozole group and 48 [89%] of 54 in the chemotherapy group) and 14 (13%) patients had intermediate-ROR disease (eight [15%] and six [11%]). Median follow-up was 200·0 days (IQR 191·2–206·0). At surgery, 23 (46·9%; 95% CI 32·5–61·7) of 49 patients in the ribociclib plus letrozole group and 24 (46·1%; 32·9–61·5) of 52 patients in the chemotherapy group were low-ROR. The most common grade 3–4 adverse events in the ribociclib plus letrozole group were neutropenia (22 [43%] of 51 patients) and elevated alanine aminotransferase concentrations (ten [20%]). The most common grade 3–4 adverse events in the chemotherapy group were neutropenia (31 [60%] of 52 patients) and febrile neutropenia (seven [13%]). No deaths were observed during the study in either group. Interpretation Our results suggest that some patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer could achieve molecular downstaging of their disease with CDK4/6 inhibitor and endocrine therapy. Funding Novartis, Nanostring, Breast Cancer Research Foundation-AACR Career Development Award.

Laser assisted chemical bath deposition (LACBD) is an interesting technique to synthesize semiconductor thin films. The effects of three laser wavelengths (445, 457 and 532 nm) on the structure, composition, morphology and optoelectronic properties of cadmium sulfide (CdS) thin films by LACBD are presented. Structural analysis of the thin films confirmed their polycrystalline nature. The surface composition specifics and chemical states of Cd and S were studied by X-ray photoelectron spectra. The topography and roughness of the films were explored by atomic force microscopy. The films exhibited high transmittance in visible region with 2.5 eV bandgap. All the samples showed photocurrent response under irradiation for white light as well as selected wavelengths of visible light emitting diodes from which the electrical properties were evaluated. The results showed that the laser irradiation by various wavelengths was effective in modification of surface topography and optoelectronic properties of the polycrystalline CdS thin films.

Pulque is a Mexican alcoholic, probiotic beverage with shelf life of 3 days. The physicochemical, probiotic, and sensory properties of pulque depend on its content of lactic acid bacteria (LAB) and yeasts. The aim of this study was to apply ohmic heating (OH) in order to extend the shelf life of pulque without altering its properties. Pulque processed by conventional pasteurization (63 °C, 30 min) was used as control. Parameters such as electrical conductivity (0.22 S/m) and optimal pasteurization conditions by OH (65 °C, 5 and 7 min; 70 °C, 3 and 5 min) were determined. Shelf life was evaluated with these parameters during 22 days of storage at 4 ± 1 °C. A higher content of LAB (6.68 and 5.96 log10 CFU/mL) was obtained at 65 °C for 5 and 7 min, respectively, compared with conventional pasteurization (3.54 log10 CFU/mL). After 22 days, physicochemical properties (pH, color, and alcohol content) were stable for both methods of pasteurization. However, the pulque treated with OH had greater sensory acceptance. For the first time, OH was used to process pulque, and results revealed that is an effective technology for extending the shelf life until 22 days, preserving microbiological and physicochemical properties. Microorganisms as surviving the OH treatments were identified as Lactobacillus acidophilus, Lactobacillus kefiri, and Saccharomyces cerevisiae.

Traffic accidents are both a major economic and public health problem worldwide. We use data from the May 2016 Spanish barometer (n = 1632) to analyse the characteristics of drivers who declare different types of risky driving behaviours. Our estimates suggest that the likelihood of being a high-risk driver in Spain increases with educational attainment and decreases with age. Moreover, it is higher for those with previous sanctions and for men, particularly so regarding speeding and driving after drinking alcohol. These results suggest that prevention policies in Spain should be targeted to different collectives of drivers depending on the particular risky behaviour considered.

Nuclear energy production generates Minor Actinide (MA) and Plutonium (Pu) isotopes, being these ones the main reason for the longtime storage of the depleted fuel assemblies. A reduction of these produced isotopes will decrease the volume required for their storage and their total elimination could eventually decrease the storage time. A possible alternative for MA reduction is recycling them into Boiling Water Reactor (BWR) cores. It is proposed that the corresponding BWR fuel assemblies into these cores will contain 4 MA bearing-rods. For this purpose a Uranium Oxide (UO2) fuel assembly or a Mixed Oxide (MOX) fuel assembly can be used. For the MOX fuel assembly two types of fuel assemblies are used, the first one only considers the replacement of 4 MOX rods by 4 MA-bearing rods and the last one considers also increasing the fuel-to moderator ratio by the replacement of 8 MOX fuel rods by water rods. The behavior of the designed fuel assemblies is compared against a reference UO2 standard 10x10 BWR fuel assembly. Results show the MA and Pu reduction achieved by the use of each one of the four proposed assemblies. Advantages and disadvantages of the recycling using each one of the fuel assemblies are discussed.

Cadmium sulfide is the main choice among n-type semiconductors for several solar cell technologies due to its excellent optical, structural and electronic characteristics. Even when it has been widely studied, there are still unsolved aspects related with the understanding of nucleation and growth mechanisms. For that, the initial growth stages of CdS deposited by chemical bath deposition (CBD) were carefully studied by in-situ X-ray photoelectron spectroscopy (XPS) by connecting a glove box with the CBD setup to the XPS introduction chamber. The CdS thin films were synthesized by CBD method onto glass substrates using CdCl2 as the cadmium precursor, sodium citrate as the complexing agent and thiourea as the sulfur source. XPS analysis revealed the presence of Cd(OH)2 and Cd-Citrate species, which facilitates nucleation to later promote the formation of CdS. During the deposition time (0–10 min) the pH changes from 12.1 to 10.8. Considering this, the following combination of mechanisms during the deposition: the hydroxide (above pH 11) and complex-decomposition (below pH 11) was proposed by using a distribution species diagram. The resulting films are close to the ideal stoichiometric CdS after 10 min of deposition. Furthermore, the film thicknesses determined by XPS ultra-thin film analysis, were about 2.37 and 13.7 nm, for 6 and 10 min, respectively, in good agreement with ellipsometry measurements.

Cobalt, nickel and zinc nanosized spinel-type ferrites (MFe2O4, M: Co2+, Ni2+ and Zn2+) were synthesized by the novel oil-in-water microemulsion method. These compounds have not been fully studied for H2 production by the water-splitting reaction, especially those prepared by microemulsion. Through proper characterization, features like crystal structure, efficient visible light absorption, high-sorption capacity and adequate textural properties, were demonstrated for thermal treated Co, Ni and Zn microemulsion synthesized nanoferrites. These characteristics favored the visible light-driven H2 production (monitored by gas chromatography) of MFe2O4 nanoparticles dispersed in water (2% MeOH), under experimental conditions. Particularly, ZnFe2O4 yielded a higher amount of H2 (354 μmolH2g−1) compared to Co (128 μmolH2g−1) and Ni (129 μmolH2g−1) ferrites in an 8 h experiment, presumably due to more favorable electronic band positions. This work represents a new contribution to the hydrogen evolution studies using ferrite nanoparticles.

Resumen Introduccion Los feocromocitomas y paragangliomas son tumores poco frecuentes cuyos sintomas mas conocidos son hipertension arterial, palpitaciones, cefalea y diaforesis. Sin embargo, su identificacion clinica no es facil. Por ello, se utilizan pruebas bioquimicas que permitan un diagnostico precoz, destacando las metanefrinas. El objetivo de este estudio fue evaluar el rendimiento diagnostico de las metanefrinas libres plasmaticas (MLP) y verificar la transferibilidad de los valores de referencia utilizados. Metodos Las MLP fueron cuantificadas mediante cromatografia liquida de alta resolucion acoplada a espectrometria de masas. Otras pruebas bioquimicas evaluadas (catecolaminas en plasma, metanefrinas, catecolaminas y acido vanilmandelico en orina) fueron analizadas por cromatografia liquida de alta resolucion con deteccion electroquimica. Se revisaron las solicitudes de dichas pruebas del 01/09/2015 al 31/10/2017 y se estimaron los valores de referencia (documento EP28-A3c) y los parametros de variabilidad biologica (metodo de Fraser) de las MLP. Resultados Se estudiaron 1.279 pacientes (61,3% mujeres), con edades entre 0-90 anos, incluyendo 19 casos de feocromocitoma/paraganglioma. Las solicitudes bioquimicas fueron: MLP (n = 662), catecolaminas urinarias (n = 589), metanefrinas urinarias (n = 586), acido vanilmandelico urinario (n = 513) y catecolaminas plasmaticas (n = 228). Las pruebas con mayor sensibilidad fueron las metanefrinas fraccionadas urinarias (91,7%) y las MLP (82,4%). Cuando se comparo el rendimiento en pacientes con ambas pruebas (n = 243), estas detectaron los mismos casos (90,9%), pero las MLP fueron mas especificas (93,5 vs. 88,8%). Para la normetanefrina plasmatica se observo una asociacion significativa con la edad (rho = 0,19; p Conclusion Las MLP y las metanefrinas fraccionadas urinarias son las pruebas bioquimicas que ofrecen un mayor rendimiento en el diagnostico de los feocromocitomas/paragangliomas.

Introduction Pheochromocytoma and paraganglioma are uncommon tumours whose best known symptoms include high blood pressure, palpitations, headache, and sweating. Clinical identification is not easy, however, and requires biochemical tests that allow for early diagnosis, including measurement of metanephrines levels. The aim of this study was to assess the diagnostic performance of plasma free metanephrines (PMETs) and to verify the transferability of the reference values used. Methods PMETs levels were measured by liquid chromatography coupled to tandem mass spectrometry. Other biochemical tests evaluated (plasma catecholamine, urine metanephrine, catecholamine and vanilmandelic acid levels) were performed by liquid chromatography with electrochemical detection. Requests of these tests from 01/09/2015 to 31/10/2017 were reviewed, and both the reference values (document EP28-A3c) and the parameters of biological variation (Fraser method) for PMETs were estimated. Results The study sample consisted of 1279 patients (61.3% females) aged 0–90 years, including 19 with pheochromocytoma/paraganglioma. Tests requested included: PMETs (n = 662), catecholamines (n = 589), metanephrines (n = 586), and vanilmandelic acid (n = 513) in urine, and plasma catecholamines (n = 228). Tests with higher sensitivity were urinary fractionated metanephrines (91.7%) and PMETs (82.4%). When performance was compared in patients with both tests (n = 243), they detected the same number of tumours (90.9%), but PMETs showed greater specificity (93.5% vs. 88.8%). Plasma normetanephrine levels showed a significant association with age (rho = 0.19, p Conclusion PMETs and urinary fractionated metanephrines are the biochemical tests with better performance in diagnosis of pheochromocytomas/paragangliomas.

A lack of automation and the high production costs entailed by the use of labor and a gelling agent limit micropropagation on a commercial scale. The aim of this study was to evaluate the temporary immersion (TI) technique in in vitro multiplication and acclimatization of Anthurium andreanum cv. Rosa. Nodal segments from in vitro-derived adventitious shoots were cultivated in different culture systems: semisolid medium, liquid medium with partial immersion and TI using an Ebb-and-Flow bioreactor. The effect of the culture system, immersion frequency, and culture medium volume per explant on shoot multiplication of A. andreanum was evaluated after 45 days of culture. In addition, chlorophyll content, stomatal index and survival rate during acclimatization were evaluated in different culture systems. A completely randomized experimental design was used for all experiments, with three replicates. An analysis of variance (ANOVA) and Tukey’s range test (p ≤ 0.05) were performed. The results showed significant differences in the variables evaluated among the different culture systems. The highest shoot production was obtained in TI with 31.50 ± 0.50 shoots per explant, followed by the partial immersion system and culture in semisolid medium, with 7.25 ± 0.16 and 4.50 ± 0.18 shoots per explant, respectively. Immersion frequency and the amount of culture medium per explant did not show significant differences, which allows us to recommend the immersion frequency of every 12 h and the culture medium volume of 25 mL per explant. TI favored an increase in chlorophyll content, a low stomatal index and a high percentage of closed stomata, suggesting an increase in the functionality of the stomata and probably a higher photosynthetic rate. The survival rate during acclimatization increased when using temporary immersion systems (TIS). This study shows for the first time an efficient TIS for commercial micropropagation of A. andreanum that produces plants with a high survival rate during acclimatization.

The forest-floor represents an important interface for various carbon dioxide (CO2) fluxes, however, our knowledge of their variability and drivers across a managed boreal forest landscape is limited. Here, we used a three-year (2016-2018) data set of biometric- and chamber-based flux measurements to investigate the net forest-floor CO2 exchange (NEff) and its component fluxes across 50 forest stands spanning different soil types, tree species, and age classes within a 68 km2 boreal catchment in Sweden. We found that the forest-floor acted as a net CO2 source with the 10th-90th percentile (used hereafter for describing reported variations) ranging from 149 to 399 g C m- 2 yr-1. Among the key landscape attributes, stand age strongly affected most NEff component fluxes, whereas tree species and soil type effects were weak and absent, respectively. Specifically, forest-floor net CO2 emissions increased with stand age due to declining understory gross and net primary production, ranging between 77-275 and 49-163 g C m- 2 yr- 1, respectively. Furthermore, we observed higher understory production rates in pine than in spruce stands. Across the 50 stands, the total forest-floor respiration ranged between 340 and 549 g C m- 2 yr-1 and its spatial variation was primarily regulated by its autotrophic components, i.e., understory and tree root respiration, which displayed divergent increasing and decreasing age-related trends, respectively. Furthermore, heterotrophic soil respiration remained within a relatively narrow range (154-290 g C m- 2 yr- 1), possibly owing to compensating gradients in forest-floor properties. We further identified tree biomass as the major driver of the landscape-scale variations of CO2 fluxes, likely attributable to modulating effects on forest-floor resource availability and growing conditions. This implies that tree growth responses to forest management and global change will be particularly important for regulating magnitudes and spatial variations of forest-floor CO2 fluxes in boreal forests.

espanolResumen La hemorragia intracerebral (HIC) representa un 20% de todos los ictus, y se produce por la extravasacion de sangre dentro del parenquima encefalico, producida por la ruptura de un vaso sanguineo. Las causas mas frecuentes son las denominadas primarias, en las que la pared de los vasos se debilita por la hipertension art erial cronica o por causas degenerativas como la angiopatia amiloide. Las causas secundarias incluyen las malformaciones vasculares, tumores o hemorragias inducidas por farmacos y drogas de abuso. Los factores de riesgo mas relevantes para padecer una HIC son hipertension arterial, tabaquismo y consumo excesivo de alcohol y drogas. Las manifestaciones clinicas de la HIC estan en funcion de la localizacion del sangrado y del volumen del hematoma. El diagnostico requiere la realizacion de una TC o RM cerebral para distinguir la HIC de una lesion isquemica u otras lesiones estructurales. La localizacion del sangrado y la presencia de microhemorragias (solo visibles en RM) permiten establecer la causa mas probable del sangrado. Estos pacientes deben ser atendidos en un hospital con unidad de ictus y su tratamiento es medico, limitandose la cirugia a un reducido y seleccionado numero de casos. EnglishIntracerebral hemorrhage (ICH) accounts for 20% of all strokes; caused by the collection of blood within the cerebral parenchyma as the result of vascular rupture. Taking into account its etiology, primary hemorrhages are the most common and are caused by the vascular wall weakness as a result of chronic arterial hypertension or due to degenerative processes as amyloid angiopathy. Secondary causes include arteriovenous malformations, tumors, hemorrhages induced by drugs and substance abuse. The most important risk factors for developing ICH are arterial hypertension, smoking, substance abuse (alcohol and drugs). Hemorrhage location and bleeding volume determine clinical manifestations. In order to distinguish between ICH and other ischemic or structural lesions, both computed tomography (CT) and magnetic resonance imaging (MRI) may be used for the diagnosis. To determine the most likely bleed cause, bleed location and microbleed detection (only detected by MRI) are necessary. Treatment for patients with ICH is fundamentally medical, and they must be cared for in a hospital with stroke unit. Surgical treatment is only recommended for a reduced number of carefully selected cases.

espanolResumen El ictus isquemico de causa inhabitual representa el 8% de los infartos y el 30% en los adultos jovenes. Se caracteriza por su heterogeneidad etiologica y puede ser la primera manifestacion de la enfermedad de base o una complicacion evolutiva mas. Los sintomas/signos asociados a la enfermedad subyacente suelen orientar el diagnostico. El tratamiento es el de la enfermedad de base, si resulta posible, y los farmacos antitromboticos. La oclusion trombotica de las venas encefalicas y senos durales es mas frecuente en adultos jovenes y predomina en las mujeres (3:1). Las trombofilias hereditarias, embarazo y puerperio, anticonceptivos orales, neoplasias, arteriopatias inflamatorias e infecciones son los principales factores de riesgo. El sintoma mas frecuente es la cefalea. Los principales sindromes de presentacion son: hipertension intracraneal aislada, encefalopatia subaguda y cuadro focal. Se trata con anticoagulantes y su pronostico es generalmente bueno. EnglishIschemic stroke of unusual causes accounts the 8% and 30% of the strokes among young adults. Etiologic heterogeneity is its main feature; it might be the first manifestation of the underlying disease or an evolutionary complication. Underlying disease-related symptoms/sings can guide the diagnosis. Treatment relies on the management of underlying disease, if possible, and antithrombotic drugs. Cerebral sinus or venous thrombotic occlusion affects mainly young adults with predominance in women (3:1). The most common risk factors are hereditary thrombophilia, pregnancy and puerperium, oral contraceptives, neoplasms, inflammatory arteriopathies and infections. Headache is the most frequent symptom. Isolated intracranial hypertension, subacute encephalopathy and focal disturbances are the main presentation syndromes. Antithrombotic treatment is required. In the most cases, prognosis is good.

This article contains data on the mechanical properties of individual cubes of caobilla wood (Swietenia humilis Zucc.) used as deformable cell of control piles, which are a special foundation system used to regulate both loads and settlements in buildings. The data were obtained from stress-controlled compression tests considering wooden cubes with different volumetric weight, moisture conditions and fiber orientation. In addition, the correlation of yield stress versus volumetric weight of caobilla wood cubes is presented. The mean values and standard deviations of volumetric weight and yield stress of the tested wooden cubes under dry and wet states are also presented.

BWR depleted fuel assemblies contain minor actinide (MA) and plutonium isotopes that must be stored for long periods of time for safety reasons, recycling of MA and plutonium is an alternative that could help to reduce the amount of high-level radioactive waste produced in a nuclear power reactor. Recycling of plutonium in MOX fuel is a proved option and several commercial reactors have MOX fuel as part of their reloads. MA recycling in a Boiling Water Reactor (BWR) has been analyzed previously by the authors showing that is feasible and the higher MA destruction is obtained when the minor actinide is embedded in uranium fuel assemblies instead of MOX fuel assemblies. However, the recycling of MA in UO2 fuel assemblies generates a higher amount of Pu-238 that is a precursor of Pu fissile isotopes increasing the amount of them in the depleted fuels employed for MA recycling. In this study a new BWR MOX fuel assembly design, that is called MOX-MA, is analyzed. The study takes an equilibrium cycle of a BWR as the reference cycle and then it proposes the use of an equivalent MOX fuel assembly in which 4 fuel rods are replaced by MA-bearing rods and 8 fuel rods are also replaced by water rods to increase moderation-to-fuel-ratio. The study aims to have the maximum amount of this new MOX BWR fuel assembly design, called MOX-MA, which can be used by reload in the core. The proposed MOX-MA fuel assembly can be used as a full reload and for a whole MOX-MA core there is no need to modify any of the control systems and this whole MOX-MA core produces the same amount of electricity than the UO2 reference equilibrium core. By using the MOX-MA fuel assemblies there is a plutonium net reduction of 33% and there is practically not production of MA.

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. The main disease hallmarks include amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core biomarkers amyloid beta 1-42, total and phosphorylated tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings. Here we evaluated 30 brain-related proteins as candidate biomarkers of AD. Proteins were quantified in CSF samples from cognitively healthy individuals (n = 23) and patients with mild cognitive impairment (MCI) due to AD (n = 20) or dementia due to AD (n = 10) using selected reaction monitoring mass spectrometry assays. APLP1 protein was increased in MCI relative to control (p 0.001). The best discrimination between MCI vs. controls was observed with a model combining APLP1 and SPP1 proteins (area under the curve, AUC = 0.84). The strongest associations between protein abundance and disease severity were found for APLP1, CNTN2 and SPP1 proteins, which had a significant correlation with MMSE and CDR tests (p 0.05). This study identifies new proteins with biomarker potential at various stages of AD severity.The current study evaluated 30 brain-related, highly specific proteins as candidate biomarkers of AD diagnosis. Protein APLP1 showed promise as early AD biomarker; protein panel APLP1 and SPP1 had the best diagnostic potential in discriminating MCI from control group, while proteins APLP1, SPP1 and CNTN2 may be indicators of disease progression, demonstrating weak to moderate correlation with cognitive tests. This study therefore identifies new proteins with biomarker potential at early AD stage. If the performance of proposed biomarkers is further confirmed, these proteins may add value in the clinic or clinical trial settings as diagnostic biomarkers (alone or in combination with the existing biomarkers) of the prodromal AD stage, and in monitoring disease progression.

Introduction We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. Methods All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. Results Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1000 people-year. In addition to ageing and smoking, time on ART (OR 1.11; 95% CI 1.05–1.17) and PI use (OR 1.72; 95% CI 1.0–2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99–1.0; p = 0.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08–3.92) were associated with higher mortality. Conclusions Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.

Resumen Introduccion Presentamos un estudio caso-control de tumores no definitorios de sida (TNDS) en una cohorte de pacientes infectados por el VIH en la que valoramos las tasas de incidencia, supervivencia y factores pronosticos de mortalidad. Metodos Se recogieron de forma prospectiva en 7 hospitales, los diagnosticos de TNDS realizados de 2007 a 2011, con seguimiento posterior hasta diciembre de 2013. Se seleccionaron de forma aleatoria un grupo control de 221 pacientes VIH sin diagnostico de cancer. Resultados Se diagnosticaron 221 TNDS en una cohorte inicial de 7.067 pacientes VIH. Los mas frecuentes: hepatocarcinoma 20,5%, pulmon 18,7%, cabeza y cuello 11,9% y anal 10,5%. La tasa de incidencia de desarrollo de TNDS fue de 7,84/1.000 pacientes-ano. Ademas de la edad y el tabaco, el tiempo en TAR (OR 1,11; IC 95% 1,05-1,17) y el uso de IP (OR 1,72; IC 95% 1,0-2,96) aumentaron el riesgo de desarrollar un TNDS. Durante el seguimiento fallecieron el 53,42%, con una mediana de supervivencia de 199,5 dias. En el analisis de los factores pronosticos de mortalidad, los valores bajos de CD4 en el momento del diagnostico del tumor (OR 0,99; IC 95% 0,99-1,0; p = 0,033) y el diagnostico previo de sida (OR 2,06; IC 95% 1,08-3,92) se asociaron con una mayor mortalidad. Conclusiones Los predictores de TNDS en nuestra cohorte fueron la edad, el consumo de tabaco, los linfocitos CD4 y el mayor tiempo en TAR. La mortalidad es alta, siendo factores de riesgo los CD4 bajos en el momento del diagnostico del TNDS y el diagnostico previo de sida.

This article presents a methodology for the construction and use of metamodels with Deep Learning (DL) methods that are useful for making multi-criteria decisions in the design and optimization of one-way slabs. The main motivation behind this research has been to examine the possibilities of improving slab design by including this methodology in future tools, which is capable of calculating thousands of solutions in real time based on the designer’s specifications. The process of creating these metamodels begins by developing a database of millions of combinations of slab designs. These combinations are calculated with a heuristic algorithm that provides the following results: rigidity, deflection, cost per square meter, CO2 emissions and embodied energy. Once a database including the entire universe of possible solutions has been created, a metamodel is developed that is capable of “condensing” the implicit knowledge contained in the database. This metamodel is included within a Decision Support System (DSS) that produces thousands of solutions for slabs that all comply with a range of specifications designated by the design plan. Furthermore, the methodology described herein proposes the use of Pareto-optimal solutions and graphic tools to help designers make multi-criteria decisions regarding the solutions that best fit their needs. A case study is presented to illustrate this proposal: optimizing slab design in two buildings according to technical, economic and sustainability criteria. The results indicate that the multi-criteria solutions obtained would entail a significant reduction in both emissions and embodied energy as compared to mono-criteria solutions, without significantly increasing costs.