Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

Dispersive ππ→KK[over ¯] Amplitude and Giant CP Violation in B to Three Light-Meson Decays at LHCb.

The LHCb collaboration has recently reported the largest CP violation effect from a single amplitude, as well as other giant CP asymmetries in several B-meson decays into three charmless light mesons. It is also claimed that this is predominantly due to ππ→KK[over ¯] rescattering in the final state, particularly in the 1 to 1.5 GeV region. In these analyses the ππ→KK[over ¯] amplitude is by default estimated from the ππ elastic scattering amplitude and does not describe the existing ππ→KK[over ¯] scattering data. Here we show how the recent model-independent dispersive analysis of ππ→KK[over ¯] data can be easily implemented in the LHCb formalism. This leads to a more accurate description of the asymmetry, while being consistent with the measured scattering amplitude and confirming the prominent role of hadronic final state interactions, paving the way for more elaborated analyses.

Análisis coste-efectividad del implante percutáneo de válvula aórtica SAPIEN 3 en pacientes con estenosis aórtica grave sintomática / Cost-effectiveness analysis of the SAPIEN 3 transcatheter aortic valve implant in patients with symptomatic severe aortic stenosis

Introducción y objetivos: El implante percutáneo de la válvula aórtica se ha consolidado como tratamiento de la estenosis aórtica grave inoperable o de alto riesgo quirúrgico. Recientemente las indicaciones se han ampliado a riesgo intermedio y bajo. Nuestro objetivo es evaluar la eficiencia de SAPIEN 3 frente al tratamiento médico conservador (TMC) o el reemplazo quirúrgico de válvula aórtica (RVA) en pacientes sintomáticos inoperables con riesgo alto e intermedio.´Métodos: Análisis de coste-efectividad de SAPIEN 3 frente a RVA/TMC mediante un modelo de Markov (ciclos mensuales) adaptado con 8 estados definidos por la New York Hearth Association y resultados a 15 años, incluidos las complicaciones mayores y el tratamiento tras el alta hospitalaria, desde la perspectiva del Sistema Nacional de Salud. Los parámetros de efectividad se basan en los estudios PARTNER. Se incluyeron costes sanitarios (en euros de 2019) derivados del procedimiento, hospitalización, complicaciones clínicas y seguimiento. Se aplicó una tasa de descuento anual del 3% en costes y beneficios. El análisis de sensibilidad fue determinístico y probabilístico (Monte Carlo). Resultados: En comparación con el RVA (riesgo alto e intermedio) y el TMC (inoperables), el SAPIEN 3 implicó mejores resultados en las 3 poblaciones y menor estancia. Las tasas de coste-utilidad incremental fueron 5.471 (riesgo alto), 8.119 (riesgo intermedio) y 9.948 (inoperables) euros/años de vida ajustados por calidad ganados. En el análisis probabilístico, el SAPIEN 3 resultó coste-efectivo por encima del 75% de las simulaciones en los 3 perfiles. Conclusiones: En nuestro medio, el SAPIEN 3 permite un tratamiento eficiente de la estenosis aórtica grave tanto en pacientes inoperables como en riesgo alto e intermedio (AU)

Introduction and objectives: Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. Methods: We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. Results: Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. Conclusions: In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients (AU)

A Bootstrapping Method for Improving the Classification Performance of the P300 Speller

Abstract In this paper, we present a novel approach to training classifiers in a speller based on P300 potentials. The method, based on bootstrapping, is a known strategy for generating new samples, but it is rarely used in neurosciences. The study first demonstrates how the performance of the classification task (detecting P300 and Non-P300 classes) could be sub-optimal in the traditional approach. Then, a new method for taking new samples from the training data is proposed. Each classifier is re-trained using balanced sub-groups of individual P300 and non-P300 samples. Data were collected from 14 healthy subjects, using 16 electroencephalography channels. These were filtered in bandpass and decimated. Subsequently, four linear classifiers were trained using the traditional method followed by the proposed one, with 1000, 2000 and 3000 samples per class. Results indicate an improvement in the accuracy and discrimination capacity of discriminative classifiers with the proposed method, maintaining the same statistical properties between the training and test data. By contrast, for generative classifiers, there is no significant difference in the results. Therefore, the proposed method is highly recommended for training discriminative classifiers in spell-based P300 potentials.

Resumen Este artículo presenta un método novedoso para entrenar clasificadores en un deletreador basado en potenciales P300. El método, basado en bootstrapping, es una estrategia conocida para generar nuevas muestras pero escasamente implementado en neurociencias. El estudio muestra cómo el rendimiento de la detección de P300 (frente a No-P300) puede resultar sub-óptimo usando el método tradicional. Luego, se propone un nuevo método donde se toman nuevas muestras a partir de los datos de entrenamiento. Con ellas, se re-entrena al clasificador usando sub-grupos equilibrados de muestras individuales P300 y No-P300. Los datos se recolectaron de 14 sujetos sanos, usando 16 canales de electroencefalografía. Estos fueron filtrados en pasa-banda y diezmados. Posteriormente, cuatro clasificadores lineales fueron entrenados, usando primero el método tradicional y después el método propuesto, con 1000, 2000 y 3000 muestras por clase. Los resultados muestran una mejoría en la precisión y la capacidad de discriminación de clasificadores discriminativos con el método propuesto, manteniendo las mismas propiedades estadísticas entre los datos de entrenamiento y los de prueba. En contraste, para los clasificadores generativos, no existe una diferencia significativa en los resultados. Por consiguiente, el método propuesto es altamente recomendado para entrenar clasificadores discriminativos en deletreadores basados en potenciales P300.

[Neonatal intussusception]. / Invaginación intestinal neonatal.

Intussusception in infants and young children is a relatively common entity with a well defined clinical picture and a favorable outcome in most cases.The neonatal intussusceptions is extremely rare and does not have a well-defined clinical picture since its clinical manifestations vary according to the gestational time it occurs, the response of the injured intestine and the gestational age of the child concerned. Two new cases of neonatal intussusceptions are presented and a review of the world literature is performed. Given the stage of intussusceptions (pre- or postnatal) occurs and gestational age of the affected infant (preterm or term), there are three entities with clinical characteristics, topography and evolution rather different: prenatal or intrauterine intussusception, postnatal intussusception in the preterm and postnatal intussusception in the term infant.

La invaginación intestinal en el lactante y niño pequeño es una entidad relativamente frecuente, con un cuadro clínico definido y una evolución favorable en la mayoría de los casos. La invaginación intestinal neonatal es sumamente rara y no tiene un cuadro bien definido, ya que sus manifestaciones clínicas varían de acuerdo con el momento gestacional en que se produce, con la respuesta del intestino lesionado y con la edad gestacional del niño afectado. Se presentan dos nuevos casos de invaginación intestinal neonatal y se realiza una revisión de la bibliografía mundial. Teniendo en cuenta la etapa en que se produce la invaginación (pre o postnatal) y la edad gestacional del neonato afectado (prematuro o a término), se pueden distinguir tres entidades con características clínicas, topográficas y evolutivas bien diferentes: la invaginación intestinal prenatal o intraútero, la invaginación intestinal postnatal en el prematuro y la invaginación intestinal postnatal en el neonato a término.

Dermatitis atópica desde la perspectiva del paciente: desencadenantes, cumplimiento de las recomendaciones médicas y control de la enfermedad. Estudio DATOP / Patient Perspectives on Triggers, Adherence to Medical Recommendations, and Disease Control in Atopic Dermatitis: The DATOP Study

INTRODUCCIÓN Y OBJETIVOS: Conocer, desde la perspectiva del paciente, los desencadenantes de la dermatitis atópica (DA), el grado de control percibido y el cumplimiento de las indicaciones médicas y su calidad de vida relacionada con la salud (CVRS). PACIENTES Y MÉTODOS: Estudio epidemiológico, transversal, multicéntrico incluyendo pacientes adultos (> 16 años; n = 125) y pediátricos (entre 2-15 años; n = 116) con DA de intensidad moderada-grave, más de 12 meses de evolución y con episodios de lesiones activas moderados-graves (escala de evaluación global del investigador [IGA] > 2). Se analizaron los desencadenantes informados por los pacientes, el cumplimiento de las recomendaciones y el tratamiento farmacológico (TF), las diferencias en CVRS y el control percibido (U de Mann-Whitney) según la gravedad de la DA (índice SCORAD-SCORing Atopic Dermatitis). RESULTADOS: Los desencadenantes más frecuentes fueron: cosméticos, ropa, ácaros, detergentes/jabones y cambios de temperatura. El 47,2% de los pacientes adultos y el 39,7% de los pediátricos no aplicaban el TF desde el inicio del episodio. El TF, la hidratación y los consejos médicos de cuidado fueron las recomendaciones más seguidas. El 41,6 y el 27,6% (adultos y pediátricos, respectivamente) consideraba que su grado de control era insuficiente y se asoció con la gravedad de la DA en adultos (p = 0,014). CONCLUSIONES: El grado de control actual de la DA es mejorable, especialmente en adultos. Aunque los pacientes indican seguir las recomendaciones médicas, un porcentaje significativo no aplica correctamente los tratamientos. Parece necesario potenciar la educación sobre la enfermedad y su manejo para mejorar el grado de control y potenciar su CVRS

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age > 16 years; n = 125) and children (age, 2-15 years, n = 116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score > 2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27.6% of pediatric patients and, in adults, this was associated with the severity of AD (P = 0.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL

Patient perspectives on triggers, adherence to medical recommendations, and disease control in atopic dermatitis: the DATOP study.

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age >16 years; n=125) and children (age, 2-15 years, n=116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score>2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27. 6% of pediatric patients and, in adults, this was associated with the severity of AD (P=.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL.

Calidad de vida relacionada con la salud, satisfacción y cumplimiento de los pacientes con dermatitis atópica moderada-grave que siguen un tratamiento farmacológico de mantenimiento. Estudio CONDA-SAT / Health-Related Quality of Life, Patient Satisfaction, and Adherence to Treatment in Patients With Moderate or Severe Atopic Dermatitis on Maintenance Therapy: The CONDA-SAT Study

Introducción y objetivos: Evaluar la calidad de vida relacionada con la salud (CVRS), la satisfacción y cumplimiento en pacientes con dermatitis atópica (DA) moderada-grave en tratamiento farmacológico de mantenimiento. Material y métodos: Estudio epidemiológico, multicéntrico, nacional, transversal con pacientes adultos y pediátricos diagnosticados de DA moderada o grave de al menos 16 meses de evolución y en tratamiento de mantenimiento. Se aplicó el Índice de Calidad de Vida en Dermatología (DLQI), el Cuestionario Dermatológico de Calidad de Vida Infantil (CDLQI), la versión para menores de 4 años (IDQOL), la Escala de Afectación de la Dermatitis Atópica (EADA), el test de Morisky-Green y escalas visuales analógicas de satisfacción. Se comparó la CVRS entre pacientes con afectación moderada y grave (U de Mann-Whitney) y la duración y número de brotes antes y después de la terapia de mantenimiento (prueba de Wilcoxon). Resultados: Participaron 141 pacientes pediátricos y 141 adultos con DA moderada en el 85,8 y 79,4% de los casos, respectivamente. El impacto en CVRS fue leve-moderado. La duración y número de los brotes disminuyeron desde la aplicación del tratamiento de mantenimiento (p < 0,001). Aunque la satisfacción fue alta en ambos grupos, el cumplimiento fue muy bajo (entre el 18,4-42,6% en pediátricos y entre el 14,9-27,0% en adultos). Conclusiones: Los pacientes con DA moderada o grave que siguen tratamiento farmacológico de mantenimiento presentan una reducción en la duración y número de los brotes y menor afectación de su CVRS. Además, los pacientes están satisfechos con el tratamiento aunque su cumplimiento es mejorable (AU)

Objective: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. Material and methods: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months’ duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. Results: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P <0 .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). Conclusions: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved (AU)

Health-related quality of life, patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy: the CONDA-SAT study.

OBJECTIVE: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. MATERIAL AND METHODS: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months' duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. RESULTS: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P < .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). CONCLUSIONS: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved.

Does avian conspicuous colouration increase or reduce predation risk?

Animals often announce their unprofitability to predators through conspicuous coloured signals. Here we tested whether the apparently conspicuous colour designs of the four European Coraciiformes and Upupiformes species may have evolved as aposematic signals, or whether instead they imply a cost in terms of predation risk. Because previous studies suggested that these species are unpalatable, we hypothesized that predators could avoid targeting them based on their colours. An experiment was performed where two artificial models of each bird species were exposed simultaneously to raptor predators, one painted so as to resemble the real colour design of these birds, and the other one painted using cryptic colours. Additionally, we used field data on the black kite's diet to compare the selection of these four species to that of other avian prey. Conspicuous models were attacked in equal or higher proportions than their cryptic counterparts, and the attack rate on the four species increased with their respective degree of contrast against natural backgrounds. The analysis of the predator's diet revealed that the two least attacked species were negatively selected in nature despite their abundance. Both conspicuous and cryptic models of one of the studied species (the hoopoe) received fewer attacks than cryptic models of the other three species, suggesting that predators may avoid this species for characteristics other than colour. Globally, our results suggest that the colour of coraciiforms and upupiforms does not function as an aposematic signal that advises predators of their unprofitability, but also that conspicuous colours may increase predation risk in some species, supporting thus the handicap hypothesis.

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.

[Pharmacoeconomic assessment of daptomycin as first-line therapy for bacteraemia and complicated skin and skin structure infections caused by gram-positive pathogens in Spain]. / Evaluación farmacoeconómica de daptomicina como terapia de primera línea en el tratamiento de bacteriemia e infecciones complicadas de piel y tejidos blandos causadas por microorganismos grampositivos en España.

OBJECTIVE: To assess the efficiency of daptomycin as firstline therapy (D) versus daptomycin as salvage therapy after vancomycin (V→D ) or linezolid (L→D) failure in gram-positive bacteraemia and complicated skin and skin-structure infections (cSSTIs). METHODS: Cost-effectiveness analysis of 161 bacteraemia and 84 cSSTIs patients comparing the above mentioned therapeutic alternatives was performed using the data from 27 Spanish hospitals involved in the EUCORE study. Direct medical costs were considered. Patients were observed from the first antibiotic dose for infection until either the end of daptomycin therapy or exitus. A multivariate Monte Carlo probabilistic sensitivity analysis was applied for costs (lognormal distribution) and effectiveness (normal distribution). RESULTS: In terms of effectiveness there were no statistical differences between groups but referring total costs per patient, there were significant differences. Sensitivity analysis confirmed that D dominates over L→D between 44.2%-62.1% of simulations in bacteraemia and between 48.2%-67.5% in cSSTIs. In comparison to V→D, D dominance was detected in 29.2%-33.2% of simulations in bacteraemia and between 48.2%-59.3% in cSSTIs. CONCLUSIONS: Daptomycin as first-line therapy dominates over daptomycin as salvage therapy after linezolid failure both in bacteraemia and cSSTIs. Comparing daptomycin as first-line therapy with its use after vancomycin failure, in cSSTIs the former is dominant. In bacteremia daptomycin as first line therapy is as effective as daptomycin as salvage therapy after vancomycin failure and implies lower costs.

Atomistic models for free energy evaluation of drug binding to membrane proteins.

The binding of various molecules to integral membrane proteins with optimal affinity and specificity is central to normal function of cell. While membrane proteins represent about one third of the whole cell proteome, they are a majority of common drug targets. The quest for the development of computational models capable of accurate evaluation of binding affinities, decomposition of the binding into its principal components and thus mapping molecular mechanisms of binding remains one of the main goals of modern computational biophysics and related drug development. The primary scope of this review will be on the recent extension of computational methods for the study of drug binding to membrane proteins. Several examples of such applications will be provided ranging from secondary transporters to voltage gated channels. In this mini-review, we will provide a short summary on the breadth of different methods for binding affinity evaluation. These methods include molecular docking with docking scoring functions, molecular dynamics (MD) simulations combined with post-processing analysis using Molecular Mechanics/Poisson Boltzmann (Generalized Born) Surface Area (MM/PB(GB)SA), as well as direct evaluation of free energies from Free Energy Perturbation (FEP) with constraining schemes, and Potential of Mean Force (PMF) computations. We will compare advantages and shortcomings of popular techniques and provide discussion on the integrative strategies for drug development aimed at targeting membrane proteins.

Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator.

We have investigated a novel series of acid-derived γ-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent γ-secretase modulator, which lowered Aß42, increased Aß38, but had little to no effect on Aß40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain Aß42 levels in CF-1 mice and Fischer rats, as well as plasma Aß42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.

Entrenador-Simulador Avanzado para el aprendizaje y entrenamiento de la Cirugía Artroscópica insightArthroVR® / InsightArthroVR®, Advanced Arthroscopic Training Simulator

Las técnicas de cirugía mínimamente invasiva son cada vez más frecuentes. Sin embargo, estas técnicas son procedimientos costosos, complejos y difíciles de dominar. Los actuales métodos de aprendizaje presentan limitaciones y son susceptibles de ser complementados por soluciones de alta tecnología como el presente simulador de realidad virtual. El entrenamiento mediante simuladores mejora la destreza de los cirujanos en el uso del instrumental artroscópico, reduciendo el tiempo de la intervención, aumentando la seguridad y confianza del cirujano, disminuyendo el posible daño al paciente y permitiendo obtener experiencia en una gran variedad de patologías (AU)

Minimal Invasive Surgery (MIS) techniques are becoming more and more frequent. However these techniques are complex and expensive procedures difficult to master. Current learning methods have a number of limitations that can be compensated for and complemented by our virtual reality simulator. Training with simulators considerably improves surgeons’ dexterities with the arthroscopic instruments, reduces surgery times, increases surgery confidence and procedures safety, reducing the morbidity of real interventions and allowing obtaining experience in a large variety of pathologies (AU)

[Splenic epidermoid cyst: laparoscopic partial decapsulation]. / Quiste esplénico epidermoide: decapsulación parcial por vía laparoscópica.

The splenic cysts are rare among all age groups and there are a few reports in the world literature. The splenic epidermoid cyst is a true congenital one, that can cause signs and symptoms, or suffer complications. For these reasons, some form of treatment is recommended. The management of splenic cysts continues to evolve. The standard treatment was splenectomy, but the knowledge about the immunologic function of the spleen and the existence of postesplenectomy mortal sepsis, have conduced most of pediatric surgeons to adopt techniques that preserves splenic tissue. The treatment by percutaneous drainage with injection of a sclerosing agent has complications and a significant recurrence rate. During the last two decades, preservation procedures such as partial splenectomy or partial cyst excision and omental packing have gained the preference of most pediatric surgeons. The second technique has advantages over the partial splenectomy. The possibility to perform the procedure by a laparoscopic approach add the advantages of this last technique. We present two patients with splenic epidermoid cyst treated by laparoscopic partial cyst decapsulation and review the literature.

Quiste esplénico epidermoide: decapsulación parcial por vía laparoscópica / splenic epidermoid cyst: laparoscopic partial decapsulation

Los quistes esplénicos son raros a cualquier edad, existiendo pocos casos publicados en la literatura mundial. El quiste esplénico epidermoide es un quiste congénito verdadero, que en su evolución puede generar signos y síntomas, o sufrir complicaciones, por lo que es prudente algún tipo de tratamiento. El manejo de pacientes con quiste esplénico ha evolucionado en las últimas décadas. El tratamiento clásico convencional involucraba la extirpación del quiste junto con el bazo; pero el conocimiento actual de la función inmunológica del bazo y de la posibilidad de sepsis mortal postesplenectomía, ha conducido a la búsqueda de técnicas quirúrgicas que preserven el tejido esplénico. El tratamiento por drenaje percutáneo e inyección de agentes esclerosantes ha mostrado complicaciones y alto índice de recurrencia. Durante las dos últimas décadas, nuevos procedimientos con preservación del tejido esplénico, como la esplenectomía parcial con extirpación del quiste y la decapsulación parcial del quiste, han ganado la preferencia de la mayoría de los cirujanos pediátricos. La posibilidad de realizar el procedimiento por vía laparoscópica, agrega las ventajas de esta última técnica. El objetivo del trabajo es presentar dos pacientes con quistes epidermoides de bazo, tratados mediante decapsulación parcial por vía laparoscópica, y se realiza una revisión bibliográfica del tema (AU)

The splenic cysts are rare among all age groups and there are a few reports in the world literature. The splenic epidermoid cyst is a true congenital one, that can cause signs and symptoms, or suffer complications. For these reasons, some form of treatment is recommended. The management of splenic cysts continues to evolve. The standard treatment was splenectomy, but the knowledge about the immunologic function of the spleen and the existence of postesplenectomy mortal sepsis, have conduced most of pediatric surgeons to adopt techniques that preserves splenic tissue. The treatment by percutaneous drainage with injection of a sclerosing agent has complications and a significant recurrence rate. During the last two decades, preservation procedures such as partial splenectomy or partial cyst excision and omental packing have gained the preference of most pediatric surgeons. The second technique has advantages over the partial splenectomy. The possibility to perform the procedure by a laparoscopic approach add the advantages of this last technique. We present two patients with splenic epidermoid cyst treated by laparoscopic partial cyst decapsulation and review the literature (AU)

An analysis of continent-wide patterns of sexual selection in a passerine bird.

Patterns of selection are widely believed to differ geographically, causing adaptation to local environmental conditions. However, few studies have investigated patterns of phenotypic selection across large spatial scales. We quantified the intensity of selection on morphology in a monogamous passerine bird, the barn swallow Hirundo rustica, using 6495 adults from 22 populations distributed across Europe and North Africa. According to the classical Darwin-Fisher mechanism of sexual selection in monogamous species, two important components of fitness due to sexual selection are the advantages that the most attractive males acquire by starting to breed early and their high annual fecundity. We estimated directional selection differentials on tail length (a secondary sexual character) and directional selection gradients after controlling for correlated selection on wing length and tarsus length with respect to these two fitness components. Phenotype and fitness components differed significantly among populations for which estimates were available for more than a single year. Likewise, selection differentials and selection gradients differed significantly among populations for tail length, but not for the other two characters. Sexual selection differentials differed significantly from zero across populations for tail length, particularly in males. Controlling statistically for the effects of age reduced the intensity of selection by 60 to 81%, although corrected and uncorrected estimates were strongly positively correlated. Selection differentials and gradients for tail length were positively correlated between the sexes among populations for selection acting on breeding date, but not for fecundity selection. The intensity of selection with respect to breeding date and fecundity were significantly correlated for tail length across populations. Sexual size dimorphism in tail length was significantly correlated with selection differentials with respect to breeding date for tail length in male barn swallows across populations. These findings suggest that patterns of sexual selection are consistent across large geographical scales, but also that they vary among populations. In addition, geographical patterns of phenotypic selection predict current patterns of phenotypic variation among populations, suggesting that consistent patterns of selection have been present for considerable amounts of time.