Next-generation sequencing of uveal melanoma with clinical and histological correlations: Prognostic value of new mutations in the PI3K/AKT/mTOR pathway.

BACKGROUND: Uveal melanoma (UM) is the eye's most common primary malignancy and there are no effective therapies for disseminated disease. It is important to try to know the patient's prognosis. The aim of this study was to reflect genetic variants, studied using NGS, of a series of 69 cases of UM and its correlation with histopathology and clinical progression. METHODS: We performed targeted NGS using a 519-gene panel. RESULTS: There were selected 28 different mutated genes, showing a total of 231 genetic variants that affected the function of the protein. The most common secondary mutations occurred in SF3B1 (in 26%), followed by BAP1 (in 23%), LRP1B (22%) and FGFR4 (20%). BAP1 mutation was associated with a greater likelihood of metastases and with greater presence of epithelioid cells. LRP1B was also associated with presence of epithelioid cells SF3B1 mutation was significantly associated with a spindle morphology. We found variants in the RAD51B, TOP2A, PTPRD, TSC2, DHX9, PDK1 and MTOR that have not been previously reported in consulted databases. The presence of a mutation in: CHEK2, DHX9 and PDK1 was associated with metastases. CONCLUSIONS: BAP1 is the most solid biomarker of a poor prognosis in UM and mutations can be detected using NGS. SF3B1 is associated with the spindle cell subtype of UM, which gives it probably a favourable prognostic value. Our study suggests that mutations in DHX9 and PDK1 can have prognostic value. These potential biomarkers are related to the PI3K/AKT/mTOR pathway and makes them candidates for developing new directed therapies.

Use of Artificial Neural Networks as a Predictive Tool of Dissolved Oxygen Present in Surface Water Discharged in the Coastal Lagoon of the Mar Menor (Murcia, Spain).

The Mar Menor is a Mediterranean coastal saltwater lagoon (Murcia, Spain) that represents a unique ecosystem of vital importance for the area, from both an economic and ecological point of view. During the last decades, the intense agricultural activity has caused episodes of eutrophication due to the contribution of inorganic nutrients, especially nitrates. For this reason, it is important to control the quality of the water discharged into the Mar Menor lagoon, which can be performed through the measurement of dissolved oxygen (DO). Therefore, this article aimed to predict the DO in the water discharged into this lagoon through the El Albujón watercourse, for which two theoretical models consisting of a multiple linear regression (MLR) and a back-propagation neural network (RPROP) were developed. Data of temperature, pH, nitrates, chlorides, sulphates, electrical conductivity, phosphates and DO at the mouth of this watercourse, between January 2014 and January 2021, were used. A preliminary statistical study was performed to discard the variables with the lowest influence on DO. Finally, both theoretical models were compared by means of the coefficient of determination (R2), the root mean square errors (RMSE) and the mean absolute error (MAE), concluding that the neural network made a more accurate prediction of DO.

Application of Concretes Made with Glass Powder Binder at High Replacement Rates.

Glass is a material that can be reused, except for a small part that, due to its residual characteristics, cannot be reused and becomes a nonbiodegradable waste to accumulate in landfills. The chemical composition and pozzolanic properties of waste glass are encouraging for the use of these wastes in the cement and concrete industries and for providing technically and environmentally viable solutions. In this study, we propose the production of deactivated concretes with a high content of glass powder in the binder. The substitution percentage of glass powder for cement used in this work was between 70% and 80%. Consistency, air content, bulk density, workability, compression strength, and permeability tests were performed. Regarding compressive strength, the results obtained at 90 days for percentages of cement substitution by glass powder of 70 and 80%, respectively, were 14.2 and 8.6. The chemical analysis of leachates showed concentrations of Fe, Cu, V, Ni, and Mo, in mg L-1, of 1.57, 1.38, 0.85, 0.95, and 0.44, respectively. The results obtained, compared with the relevant legislation, have proved that the inclusion of glass powder in a high percentage of substitution and with a granulometry of 20 µm in the manufacture of deactivated concretes is feasible for exterior pavements.

Eco-Friendly Pavements Manufactured with Glass Waste: Physical and Mechanical Characterization and Its Applicability in Soil Stabilization.

The use of glass waste, which by its nature cannot be recycled, might be a viable alternative in the manufacture of cements and concrete that is also economical and environmentally friendly. This alternative can reduce landfill areas with this inert residue but also limit the use of raw materials employed in the manufacture of cement and concrete and, consequently, contribute to minimize the environmental impact generated by this activity. In this research, the feasibility of using a limestone-type material treated with a binder manufactured with micronized glass powder and basic reagents, in the preparation of a gravel-cement- or soil-cement-type material, was analyzed. For this purpose, the strength, compactability, structural capacity, resistance to the action of water, stiffness and durability of the material obtained were characterized. From the tests that were carried out and the results obtained, it can be concluded that the use of glass powder, with a particle size of 16 µm, is ideal for the production of a gravel-cement- or soil-cement-type material. This material could be used as an environmentally-friendly pavement, especially suitable for peri-urban roads and park roads, where it can be used without coating, or as a base layer or sub-base for road surfaces, with little cracking due to shrinkage.

Sistema combinado de depuración de CO2 y reemplazo renal continuo / Extracorporeal CO2 Removal in Combination with Continuous Renal Replacement Therapy

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Coumarin Derivatives Solvent-Free Synthesis under Microwave Irradiation over Heterogeneous Solid Catalysts.

A suitable methodology of synthesis of coumarin derivatives by Pechmann reaction over heterogeneous solid acid catalysts in a free solvent media under microwave irradiation is described. Resorcinol, phenol and ethyl acetoacetate were selected as model reactants in the Pechmann condensation. The catalytic activity of several materials-Amberlyst-15, zeolite ß and sulfonic acid functionalized hybrid silica-in solvent-free microwave-assisted synthesis of the corresponding coumarin derivatives has been investigated in detail. 7-Hydroxy-4-methylcoumarin and 4-methylcoumarin were obtained in 97% and 43% yields, respectively, over Amberlyst-15. This was the most active catalyst in the Pechmann reaction under studied conditions.

FT-Raman and NIR spectroscopy data fusion strategy for multivariate qualitative analysis of food fraud.

Two data fusion strategies (high- and mid-level) combined with a multivariate classification approach (Soft Independent Modelling of Class Analogy, SIMCA) have been applied to take advantage of the synergistic effect of the information obtained from two spectroscopic techniques: FT-Raman and NIR. Mid-level data fusion consists of merging some of the previous selected variables from the spectra obtained from each spectroscopic technique and then applying the classification technique. High-level data fusion combines the SIMCA classification results obtained individually from each spectroscopic technique. Of the possible ways to make the necessary combinations, we decided to use fuzzy aggregation connective operators. As a case study, we considered the possible adulteration of hazelnut paste with almond. Using the two-class SIMCA approach, class 1 consisted of unadulterated hazelnut samples and class 2 of samples adulterated with almond. Models performance was also studied with samples adulterated with chickpea. The results show that data fusion is an effective strategy since the performance parameters are better than the individual ones: sensitivity and specificity values between 75% and 100% for the individual techniques and between 96-100% and 88-100% for the mid- and high-level data fusion strategies, respectively.

A tutorial on the validation of qualitative methods: from the univariate to the multivariate approach.

This tutorial provides an overview of the validation of qualitative analytical methods, with particular focus on their main performance parameters, for both univariate and multivariate methods. We discuss specific parameters (sensitivity, specificity, false positive and false negative rates), global parameters (efficiency, Youden's index and likelihood ratio) and those parameters that have a quantitative connotation since they are usually associated to concentration values (decision limit, detection capability and unreliability region). Some methodologies that can be used to estimate these parameters are also described: the use of contingency tables for the specific and global parameters and the performance characteristic curve (PCC) for the ones with quantitative connotation. To date, PCC has been less commonly used in multivariate methods. To illustrate the proposals summarized in this tutorial, two cases study are discussed at the end, one for a univariate qualitative analysis and the other for multivariate one.

Partial least squares density modeling (PLS-DM) - a new class-modeling strategy applied to the authentication of olives in brine by near-infrared spectroscopy.

A new class-modeling method, referred to as partial least squares density modeling (PLS-DM), is presented. The method is based on partial least squares (PLS), using a distance-based sample density measurement as the response variable. Potential function probability density is subsequently calculated on PLS scores and used, jointly with residual Q statistics, to develop efficient class models. The influence of adjustable model parameters on the resulting performances has been critically studied by means of cross-validation and application of the Pareto optimality criterion. The method has been applied to verify the authenticity of olives in brine from cultivar Taggiasca, based on near-infrared (NIR) spectra recorded on homogenized solid samples. Two independent test sets were used for model validation. The final optimal model was characterized by high efficiency and equilibrate balance between sensitivity and specificity values, if compared with those obtained by application of well-established class-modeling methods, such as soft independent modeling of class analogy (SIMCA) and unequal dispersed classes (UNEQ).

Validation of multivariate screening methodology. Case study: detection of food fraud.

Multivariate screening methods are increasingly being implemented but there is no worldwide harmonized criterion for their validation. This study contributes to establish protocols for validating these methodologies. We propose the following strategy: (1) Establish the multivariate classification model and use receiver operating characteristic (ROC) curves to optimize the significance level (α) for setting the model's boundaries. (2) Evaluate the performance parameter from the contingency table results and performance characteristic curves (PCC curves). The adulteration of hazelnut paste with almond paste and chickpea flour has been used as a case study. Samples were analyzed by infrared (IR) spectroscopy and the multivariate classification technique used was soft independent modeling of class analogies (SIMCA). The ROC study showed that the optimal α value for setting the SIMCA boundaries was 0.03 in both cases. The sensitivity value was 93%, specificity 100% for almond and 98% for chickpea, and efficiency 97% for almond and 93% for chickpea.

Multivariate screening in food adulteration: untargeted versus targeted modelling.

Two multivariate screening strategies (untargeted and targeted modelling) have been developed to compare their ability to detect food fraud. As a case study, possible adulteration of hazelnut paste is considered. Two different adulterants were studied, almond paste and chickpea flour. The models were developed from near-infrared (NIR) data coupled with soft independent modelling of class analogy (SIMCA) as a classification technique. Regarding the untargeted strategy, only unadulterated samples were modelled, obtaining 96.3% of correct classification. The prediction of adulterated samples gave errors between 5.5% and 2%. Regarding targeted modelling, two classes were modelled: Class 1 (unadulterated samples) and Class 2 (almond adulterated samples). Samples adulterated with chickpea were predicted to prove its ability to deal with non-modelled adulterants. The results show that samples adulterated with almond were mainly classified in their own class (90.9%) and samples with chickpea were classified in Class 2 (67.3%) or not in any class (30.9%), but no one only as unadulterated.

Consideraciones sobre el parto en una paciente con miocardiopatía hipertrófica y desfibrilador automático implantable / Considerations on delivery in a patient with hypertrophic myocardiopathy and an implantable cardioverter-defibrillator

La miocardiopatía hipertrófica es una enfermedad hereditaria autosómica dominante, que puede ser diagnosticada durante el embarazo. Teniendo en cuenta que la cardiopatía en el embarazo es la primera causa de morbimortalidad materna de causa no obstétrica, presentamos un caso de una gestante de 26 años con miocardiopatía hipertrófica, y portadora de desfibrilador automático implantable, discutiendo los aspectos más importantes en cuanto al manejo de este tipo de pacientes durante el parto, el preparto y el posparto inmediato (AU)

Hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and can be diagnosed during pregnancy. Cardiomyopathy is the leading cause of nonobstetric maternal morbidity and mortality. We present the case of a 26-year-old pregnant woman with hypertrophic cardiomyopathy and an automatic implantable cardioverter defibrillator and we discuss the most important therapeutic considerations in the management of these patients before and during delivery and in the immediate postpartum period (AU)

Figures of merit of a SERS method for Sudan I determination at traces levels.

A substrate for Surface-Enhanced Raman Scattering spectroscopy (SERS), electropolished Al, is proposed as a tool for a rapid and low cost determination of Sudan I. This dye has been used as an additive in some foodstuffs but it is now banned because of the health risk associated with its carcinogenic and mutagenic properties. Despite the presence of fluorescence, Raman spectra of Sudan I can be obtained using excitation lasers at 633 and 785 nm. To get rid of the spectral noise and fluorescence background, Savitzky-Golay smoothing and polynomial corrections were applied, respectively. The Raman signal was proved to be enhanced. A linear dependence was found between the logarithmic intensity at 1598 cm(-1) peak versus the logarithmic concentration. The figures of merit were studied obtaining high sensitivity and low detection limits (10(-7) M). A multivariate exploratory analysis (PCA) was used to study the ability of SERS to distinguish Sudan I from other similar compounds. Therefore, results show that SERS is a potential tool to determine Sudan I quickly and effectively.

Terapia cognitivo-conductual en las psicosis agudas / Cognitive-behavioral therapy for acute psychosis

El tratamiento de las psicosis agudas era, hasta hace unos años, algo relegado al tratamiento farmacológico (a excepción del psicoanálisis). En los últimos tiempos esta tendencia ha ido cambiando y diversos estudios han puesto de manifiesto la ventaja de las intervenciones cognitivo conductuales en las fases agudas de las psicosis. A esta tendencia se ha unido un nuevo y prometedor paradigma de intervención, la intervención temprana en psicosis (AU)

Some years ago, the treatment for acute psychosis was something left for pharmacological treatment (except for psychoanalysis). Lately, this trend has been changing and some studies have shown the advantages of cognitive behavioural therapy in the acute psychosis. A new and promising way of intervention is merging to this trend: early intervention of psychosis (AU)

New ru(II) complexes containing oxazoline ligands as epoxidation catalysts. Influence of the substituents on the catalytic performance.

The synthesis of a family of new Ru complexes containing the facial tridentate ligand with general formula [Ru(II)(T)(D)(X)](n+) (T = trispyrazolylmethane (tpm); D = ((4S,4'S)-(-)-4,4',5,5'-tetrahydro-4,4'-bis(1-methylethyl)-2,2'-bioxazole) (iPr-box-C) or N-(1-hydroxy-3-methylbutan-(2S)-(-)-2-yl)-(4S)-(-)-4-isopropyl-4,5-dihydrooxazole-2-carbimidate (iPr-box-O); X = Cl, H(2)O) has been described. All complexes have been spectroscopically characterized in solution through (1)H NMR and UV-vis techniques, and the redox properties of complexes have also been studied by means of cyclic voltammetry (CV). Furthermore, the chloro complexes presented here have been characterized in the solid state through monocrystal X-ray diffraction analysis. The oxazolinic iPr-box-C ligand undergoes a Ru-assisted hydrolysis reaction generating the corresponding amidate anionic ligand iPr-box-O, that keeps coordinated to the Ru metal center and that produces a strong σ-donation effect over it. The reactivity of the Ru-OH(2) complexes described in this paper together with other similar ones, previously synthesized by us, has been tested with regard to the epoxidation of different olefins. Complexes [Ru(II)(R-box-C)(tpm)OH(2)](BF(4))(2), R = Bz, 3'c/iPr, 3c, show high stereoselectivity in the epoxidation of cis-ß-methylstyrene, with the exclusive formation of the cis-epoxide. However, there is a significant difference in regioselectivity between the two catalysts in the epoxidation of 4-vinylcyclohexene; complex 3'c leads to the regioselective oxidation at the ring alkene position, whereas complex 3c leads to the oxidation at the terminal position. Computational calculations indicate only small energy differences between the two possible products of 4-vinylcyclohexene epoxidation, but the energy barriers for the interaction of the catalytic systems with the alkene groups of 4-vinylcyclohexene agree with the reactivity differences found for the two catalysts having isopropyl or benzyl as substituent of the oxazole ligand. Computed local Fukui functions help to explain the observed reactivity trends.

Study of organo-hybrid layered double hydroxides by medium and near infrared spectroscopy.

An Mg/Al layered double hydroxide (LDH) containing carbonate ion in its interlayer region was examined by medium infrared (MIR) and near infrared reflectance spectroscopy (NIRS). The MIR and NIR spectroscopy techniques was also used to study two organo-hybrid LDHs containing interlayer dodecylbenzenesulphonate (DBS) and dodecylsulphate (DS) ions, respectively. The NIR spectra for the latter solids were found to exhibit the overtone and combination bands for the hydroxyl groups in addition to those typical bands of the organic host functions.

New Ru(II) complexes with anionic and neutral N-donor ligands as epoxidation catalysts: an evaluation of geometrical and electronic effects.

The synthesis of a family of new Ru complexes containing the meridional trpy ligand with general formula [Ru(II)(T)(D)(X)](n+) (T = 2,2':6',2''-terpyridine (trpy); D = 3,5-dimethyl-2-(2-pyridyl)pyrrolate (pyrpy), and 2-(1-Methyl-3-pyrazolyl)pyridine (pypz-Me); X = Cl, H(2)O) have been described. All complexes have been spectroscopically characterized in solution through (1)H NMR and UV-vis techniques, and the chloro complexes have also been characterized in the solid state through monocrystal X-ray diffraction analysis. The pyrpy ligand undergoes an oxidation at the 3-position of the pyrrolate ring during the formation of the corresponding aqua complex thus generating the analogous compound containing the oxidized ligand pyrpy-O. The redox properties of all complexes have also been studied by means of CV and DPV techniques, where both geometrical (trans vs cis) and electronic (neutral vs anionic) effects can be unveiled and rationalized. Finally, the reactivity of the whole set of Ru-OH(2) complexes has been tested with regard to the epoxidation of different alkenes with PhI(OAc)(2). In all cases good selectivities and conversions were obtained. Furthermore, total retention of the initial cis configuration was achieved when using these catalysts to epoxidize cis-beta-methylstyrene.

[To identify primary care interventions that reduce hospitalisation of people over 65 due to ambulatory care sensitive conditions]. / Intervenciones sanitarias en atención primaria que disminuyen la hospitalización por Ambulatory Care Sensitive Conditions en mayores de 65 años.

OBJECTIVES: To study how primary care (PC) professionals perceive the pathologies that tend to cause hospitalisation of people over 65 most frequently, and to study their consistency with the list of ACSCs (Ambulatory Care Sensitive Conditions). To identify prior PC interventions that could reduce or prevent hospitalisation due to those pathologies. DESIGN AND METHOD: A Delphi study with PC experts from 7 health care centres in Granada, Spain, during 2005. A descriptive analysis of the consensus obtained via self-administered questionnaires. RESULTS: The diseases that cause the bulk of admissions in people over 65 are: acute COPD, non-compensated cardiac failure, cerebro-vascular accident, and falls-traumas. The pathologies analysed form part of the list of ACSCs, with the exception of falls, listed as the fourth cause, and cancer processes, listed as the sixth cause. The hospitalisation rates that could be avoided with prompt and effective PC varies between 20% for cancer processes to 70% for non-compensated diabetes. The rate is over 50% in COPD, digestive haemorrhages, and diabetes. The key interventions for reducing hospitalisations are primary prevention care, early diagnosis, and correct treatment. Effectiveness and feasibility vary widely for each particular intervention. CONCLUSIONS: The principal causes of hospitalisation in people over 65 are included as ACSC. Priority actions to reduce avoidable hospitalisations from PC are multi-modal interventions, the majority of which are over 50% effective and feasible.

Intervenciones sanitarias en atención primaria que disminuyen la hospitalización por Ambulatory Care Sensitive Conditions en mayores de 65 años / To identify primary care interventions that reduce hospitalisation of people over 65 due to ambulatory care sensitive conditions

Objetivos. Estudiar la percepción de los profesionales de atención primaria (AP) sobre las enfermedades que con mayor frecuencia provocan hospitalizaciones en mayores de 65 años, analizar la concordancia con el listado ACSC (Ambulatory Care Sensitive Conditions) e identificar las intervenciones prioritarias que podrían reducir o evitar dicha hospitalización. Diseño y método. Estudio Delphi con expertos de AP procedentes de 7 centros de salud de Granada durante 2005. Análisis descriptivo del consenso obtenido mediante cuestionarios autoadministrados. Resultados. Las enfermedades que causan en mayor medida ingresos en mayores de 65 años son: enfermedad pulmonar obstructiva crónica (EPOC) agudizada, insuficiencia cardíaca descompensada, accidente cerebrovascular y caídas-traumatismos. Las enfermedades analizadas forman parte del listado de ACSC salvo las caídas y los procesos cancerosos. El porcentaje estimado de hospitalizaciones evitables desde AP oscila entre el 20% para procesos cancerosos y el 70% para las descompensaciones diabéticas, y es superior al 50% para la EPOC, las hemorragias digestivas y la diabetes. Las intervenciones prioritarias para disminuir los ingresos hospitalarios abarcan la prevención primaria, el diagnóstico precoz y el tratamiento correcto, con una gran variabilidad en la efectividad y la factibilidad percibida para cada intervención concreta. Conclusiones. Las principales causas de ingresos hospitalarios en mayores de 65 años están incluidas como ACSC. Las actuaciones prioritarias para reducir las hospitalizaciones evitables desde AP son intervenciones mixtas a las que, en su mayor parte, se les atribuye una efectividad y una factibilidad superiores al 50%

Objectives. To study how primary care (PC) professionals perceive the pathologies that tend to cause hospitalisation of people over 65 most frequently, and to study their consistency with the list of ACSCs (Ambulatory Care Sensitive Conditions). To identify prior PC interventions that could reduce or prevent hospitalisation due to those pathologies. Design and method. A Delphi study with PC experts from 7 health care centres in Granada, Spain, during 2005. A descriptive analysis of the consensus obtained via self-administered questionnaires. Results. The diseases that cause the bulk of admissions in people over 65 are: acute COPD, non-compensated cardiac failure, cerebro-vascular accident, and falls-traumas. The pathologies analysed form part of the list of ACSCs, with the exception of falls, listed as the fourth cause, and cancer processes, listed as the sixth cause. The hospitalisation rates that could be avoided with prompt and effective PC varies between 20% for cancer processes to 70% for non-compensated diabetes. The rate is over 50% in COPD, digestive haemorrhages, and diabetes. The key interventions for reducing hospitalisations are primary prevention care, early diagnosis, and correct treatment. Effectiveness and feasibility vary widely for each particular intervention. Conclusions. The principal causes of hospitalisation in people over 65 are included as ACSC. Priority actions to reduce avoidable hospitalisations from PC are multi-modal interventions, the majority of which are over 50% effective and feasible