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Background and Objectives. Although pets are known to be beneficial for children, they could also imply risks for immunocompromised ones. We report the prevalence of children and young patients living with pets in a cohort of immunosuppressed pediatric patients and describe risk behaviors for acquiring zoonosis and compliance with veterinary recommendations. Methods. A cross-sectional, observational study was performed in a large tertiary hospital in Madrid, including immunosuppressed patients from different regions of Spain. The participants were asked to complete an online questionnaire. Results. Two hundred and eighty-four responses were received: 62.3% solid organ transplantation (177/284), 22.8% hematopoietic stem cell transplantation (65/284), and 14.8% inborn errors of immunity (42/284). The median age was 11 years (interquartile range 5.9–15.4), and 55% were boys (156/284). Up to 45% (130/284) of the respondents lived with 201 pets (74% of them dogs and cats). Half of the patients owning dogs or cats did not comply with at least one of the recommendations regarding vaccination, deworming, feeding, and/or veterinarian recommended controls. The poorest findings were related to deworming regimens. Only 42.8% (117/273) of the participants received specific recommendations from their healthcare professionals about companion animals. However, up to 97% of the families considering acquiring a pet did so when the professional did not contraindicate it (31/32), while 72% of the families having pets got rid of their pets when they were advised against animals (8/11). Conclusions. Pet ownership is frequent among immunocompromised children. They presented risky exposures for acquiring zoonoses, and basic veterinary recommendations were not frequently followed. The opinion of professionals significantly influenced the decision to acquire pets, but less than half of the families received recommendations in this regard. Spanish Pediatrics Association (AEP) (2021 Research Grant) MAPFRE Foundation Carlos III Health Institute - Fondos Feder (BAE21/00022) 4.521 Q1 JCR 2021 0.990 Q1 SJR 2022 No data IDR 2021 UEM

Summary Ensuring cement sheath placement is of paramount importance for the success of a primary cementing operation. Poor mud displacement and fluid contamination can lead to cement isolation failure, loss of production, and even well abandonment. Over time, many cement placement computerized models have been developed, leading to a significant number of theoretical and case history papers. However, using these to design a cement job is difficult because their physical and mathematical assumptions are most of the time unclear, and because their application requires balancing precision with computation time. Models that are too precise may lead to very long runs, while oversimplified models could result in nonpredictive simulations. To the authors’ knowledge, nothing has been published to explain how to perform efficient predictions with a cement placement computerized model. Such is the object of this paper. It presents an extensive analysis of all the available cement placement computerized models, highlighting their advantages and disadvantages and listing their assumptions. This analysis indicates that (1) the actual methods used to estimate the equivalent circulating density window are not rigorous enough; (2) there still exist a lot of uncertainties when predicting the tubular standoff; (3) modeling fluid contamination, especially when the fluids are not compatible, remains very cumbersome, if not impossible, because the true interfaces’ physics is not completely considered; (4) a local contamination observed at an intermediate time can disappear at the end of the simulation due to numerical diffusion, meaning that just looking at the concentration maps at the end of placement is not sufficient to judge the efficiency of a displacement scenario; and (5) changes in geometries along the cement sheath are not considered with precision. This work allows establishing guidelines to help understanding how to manage simulation inputs and analyzing and communicating the produced results.

Hearing loss is a highly prevalent condition in the pediatric population. Pediatric maxillary expansion is a widespread treatment to address transverse maxillary deficiency. First reports describing an association between improvements for patients with HL and PME initiated in the 1960s. In this systematic review and meta-analysis we aim to review the role of maxillary expansion in reducing conductive hearing loss in pediatric population.Pubmed (Medline), the Cochrane Library, EMBASE and Trip Database were checked. Main outcome was expressed as the difference between air-bone gap, compliance, ear volume and conductive hearing thresholds before and after treatment and the 95% confidence interval.A total of 10 studies (218 patients) met inclusion criteria. The pooled data in the meta-analysis under a random effects model shows a statistically significant difference of 10.57dB mean reduction after palatal expansion. The air-bone gap was significantly reduced by 5.39dB (CI 95% 3.68, 7.10). Compliance and volume were assessed in three studies, with a non-significant positive difference in the compliance (0.14) and a statistically significant difference for volume (0.80) after palatal expansion.This systematic review and meta-analysis found a positive effect of pediatric maxillary expansion in conductive hearing loss in well-select children. However, results cannot be extrapolated for children with conductive hearing loss without an accompanying orthodontic indication (maxillary constriction). It showed that the existing prospective studies exhibited qualitative pitfalls, limiting the ability to obtain conclusive evidence about the role of pediatric maxillary expansion on conductive hearing loss in children.

This paper presents a surrogate modelling technique based on domain partitioning for Bayesian parameter inference of highly nonlinear engineering models. In order to alleviate the computational burden typically involved in Bayesian inference applications, a multielement Polynomial Chaos Expansion based Kriging metamodel is proposed. The developed surrogate model combines in a piecewise function an array of local Polynomial Chaos based Kriging metamodels constructed on a finite set of non-overlapping subdomains of the stochastic input space. Therewith, the presence of non-smoothness in the response of the forward model (e.g.~ nonlinearities and sparseness) can be reproduced by the proposed metamodel with minimum computational costs owing to its local adaptation capabilities. The model parameter inference is conducted through a Markov chain Monte Carlo approach comprising adaptive exploration and delayed rejection. The efficiency and accuracy of the proposed approach are validated through two case studies, including an analytical benchmark and a numerical case study. The latter relates the partial differential equation governing the hydrogen diffusion phenomenon of metallic materials in Thermal Desorption Spectroscopy tests.

The use of prebiotics and probiotics to improve symptoms associated with autism spectrum disorder (ASD) has varied from study to study, indicating the complex and heterogeneous nature of the disorder and the behaviors and gastrointestinal symptoms associated with ASD. There is a wide variety in the severity of symptoms and developmental impediments across the population. Gut microbiome studies have also shown unique but varied microbial signatures in ASD. While there have been successes in pre-clinical and clinical trials with prebiotic and probiotic components, the limited population sizes have promising yet inconclusive results. This study addresses this issue by 1) enrolling an ASD cohort of 296 children and adults and comparing their deep DNA metagenomic sequencing of gut microbiomes to that of an age-matched neurotypical cohort and 2) individually formulating a precision synbiotic (probiotic and prebiotic) tailored towards each individual’s needs and conducting pre/post evaluations of ASD and GI symptoms and longitudinal whole genome microbiome sequencing. At baseline, there was significantly lower microbiome diversity in the ASD group relative to controls. Microbes, pathways, and gene families significantly differed between the two populations. The ASD microbiome had higher abundances of pathogens, such asShigella, Klebsiella, Mycobacterium, andClostridium, but lower abundances of beneficial microbes, includingFaecalibacterium. With a 3-month synbiotic supplementation, the microbiome diversity of the 170 ASD participants completing the study increased and became closer to the neurotypical controls. Significant shifts in microbial and pathway abundances were also measured at the second ASD timepoint. In addition to changes in the gut microbiome, there was a significant reduction in gastrointestinal discomfort. There were also improvements in some ASD-related symptoms; however, we cannot exclude that these were potentially due to the open-label nature of the study. Changes in the gut microbiome composition and functional capacity, along with a reduction in gastrointestinal symptoms and potential changes in behavior, highlight the importance of metagenomics, longitudinal studies, and the potential for therapeutic microbial supplementation in ASD.

Resumen Presentamos un caso de macrovaso congenito retiniano estudiado mediante retinografia, campo visual, angiografia fluoresceinica y tomografia optica de coherencia macular. El macrovaso atravesaba el meridiano horizontal, nasalmente entre papila y macula. Ademas, se realiza una revision de los macrovasos congenitos retinianos, las alteraciones visuales y estructurales que causan su asociacion con otras enfermedades y su diagnostico diferencial.

Although several numerical techniques have been recently developed for the prediction of the geosynthetic-reinforced pavements performance, it is often unclear how to quantify such properties, specially when the soil is anisotropic and highly heterogeneous. In this work, following Hashin-Shtrikman bounds, explicit expressions describing anisotropic linear elastic moduli of geosynthetic-reinforced soils are presented. Modelling the geosynthetic material by oblate spheroids with spheroidal distribution inside the matrix of asphalt, the derived expressions provide bounds as a function of laminated material geometry and first principles in the elastic setting. The scheme developed can straightforwardly be extended to multiphase composites. We illustrate the implementation of the model by showing reasonable predictions on the transversely isotropic behaviour of the heterogeneous pavement.

This article presents the microneedles analysis where the design parameters studied were length, inner and outer diameter range. The ANSYS software was used to analyze the mechanical behavior of the microneedles. Following this, the range of inner and outer diameters were completed by mechanical simulations, getting from 30 μm to 134 μm, as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regression, with a correlation of 0,9993. This mathematical model generalizes the relationship of the inner diameter to the outer diameter within the ranges, ensuring a safety factor of four, where Von Misses forces of the microneedle are around 17.931 MPa. In addition, the microneedle concept was made by 3D printing using a biocompatible resin of class 1. The features presented by the microneedle designed in this work make it a promising option to be implemented in a transdermal drug delivery device.

Isolated limb perfusion (ILP) is a method for treating unresectable lesions of limbs in patients with melanoma or sarcoma by using high doses of tumor necrosis factor alpha and melphalan. This high doses can result in high systemic toxicity if there is a drug leak from the isolated circulation of the limb to the systemic. This makes it imperative to monitor the leakage rate (F(%)) during the infusion, currently performed with radiotracers. The objective of this work was to develop a leakage monitoring protocol as accurate as possible to ensure safe ILP. Material and method We built a phantom with three compartments (body, limb and precordial area) and a high sensitivity collimator fitted to a portable gamma camera. We simulate ILP with scheduled leaks every 10 min from 1% to 9% (theorical F(%)). We mesured F(%) using two equation: one is the proposed in the literature and another corrected by decay of the radioisotope. We test the optimal radiopharmaceutical doses to minimize the detector dead time error and compare F(%) mesured by both equations regarding the theoretical F(%). The leakage monitoring protocol was used in 17 ILP of 16 patients and an analysis of the recorded data was performed. Results We found significant differences between F(%) mesured using the first equation and theoretical F(%), obtaining results very adjusted to the theorical after applying the decay correction. Conclusions the decay correction of the radioisotope is a simple manner to carry out the procedure more safely, reducing the error in the calculation of F(%).

Resumen La perfusion de miembro aislado (PMA) es un metodo para el tratamiento de extremidades con lesiones irresecables de pacientes con melanoma o sarcoma. Se usan altas dosis de factor de necrosis tumoral α y melfalan, que pueden provocar toxicidad sistemica severa en caso de fuga del farmaco desde la circulacion aislada de la extremidad a la sistemica. Esto hace imperativo monitorizar el porcentaje de fuga (F[%]) durante la perfusion, actualmente realizado con radiotrazadores. El objetivo de este trabajo fue elaborar un protocolo de monitorizacion de fuga lo mas exacto posible que garantizara una PMA segura. Material y metodo Construimos un fantoma con 3 compartimentos (cuerpo, extremidad y area precordial) y un colimador de alta sensibilidad adaptable a una gammacamara portatil. Simulamos PMA con fugas programadas cada 10 min del 1 al 9% (F[%] teoricos). Medimos estos F(%) mediante 2 ecuaciones: una propuesta en la literatura y otra corregida por decaimiento del radioisotopo. Testamos las dosis de radiofarmaco optimas para minimizar el error por tiempo muerto del detector y comparamos los F(%) medidos segun las 2 ecuaciones con los F(%) teoricos. El protocolo de monitorizacion de fuga se utilizo en 17 PMA de 16 pacientes y se analizaron los datos registrados. Resultados Encontramos diferencias significativas entre los F(%) medidos con la primera ecuacion y los F(%) teoricos, con unos resultados muy ajustados a los teoricos al aplicar la correccion por decaimiento. Conclusiones La correccion por decaimiento del radioisotopo es una manera simple de realizar el procedimiento de forma mas segura y de disminuir el error en el calculo de F(%).

The parabolic equation method provides an unrivaled combination of computational efficiency and accuracy for wave propagation problems in the geosciences in which the environment has strong vertical variations and gradual horizontal variations. The development of this approach has been an active area of research for several decades in ocean acoustics, which includes problems involving sediment layers and ice cover that support shear waves. It is demonstrated here that this progress has culminated in a parabolic equation model for fast and accurate seismic computations in laterally varying environments. The model is tested for problems involving sloping boundaries and interfaces, variable layer thickness, continuous variations of the elastic parameters within layers, and a Rayleigh wave propagating along variable topography. The seismic parabolic equation model is based on an outgoing wave equation and rational approximations of operators for generating initial conditions, propagating the solution through stratified regions that approximate a laterally varying environment, and estimating transmitted fields across the vertical interfaces between regions.

Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and particularly skeletal muscle, have lately demonstrated an active contribution to disease pathology attracting a growing interest for these tissues as therapeutic targets in ALS. In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood. This review aims to compile scientific evidence that demonstrates the role of skeletal muscle in ALS pathology and serves as reference for development of novel therapeutic strategies targeting this tissue to delay disease onset and progression. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.

ObjectiveThis study aimed to assess individual preference, symptoms and compliance between habitual use of Provox XtraFlow and the combination of Provox XtraFlow during the day and Provox Luna during the night for heat and moisture exchanger therapy in laryngectomised patients.MethodThis was an open, randomised, crossover trial for 25 days. After this first study period and a 5-day wash-out period, treatments were switched for another 25 days.ResultsA total of 28 patients were enrolled. Differences were found (p = 0.009) in the incidence of dermatological problems with XtraFlow (46.4 per cent) versus Provox Luna (14.3 per cent), as well as in the need to abandon the use of adhesives (46.4 per cent vs 10.7 per cent; p = 0.003). A total of 60.7 per cent of the patients preferred the Provox Luna system as their preference for heat and moisture exchanger therapy.ConclusionThe Provox Luna system is a viable additive to heat and moisture exchanger therapy, especially in the setting of compliance concerns and in patients who desire dermatological relief overnight.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Producción Científica, ERA5 represents the state of the art for atmospheric reanalyses and is widely used in meteorological and climatological research. In this work, this dataset is evaluated using the wind kinetic energy spectrum. Seasonal climatologies are generated for 30° latitudinal bands in the Northern Hemisphere (periodic domain) and over the North Atlantic area (limited-area domain). The spectra are also assessed to determine the effective resolution of the reanalysis. The results present notable differences between the latitudinal domains, indicating that ERA5 is properly capturing the synoptic conditions. The seasonal variability is adequate too, being winter the most energetic, and summer the least energetic season. The limited area domain results introduce a larger energy density and range. Despite the good results for the synoptic scales, the reanalysis’ spectra are not able to properly reproduce the dissipation rates at mesoscale. This is a source of uncertainties which needs to be taken into account when using the dataset. Finally, a cyclone tropical transition is presented as a case study. The spectrum generated shows a clear difference in energy density at every wavelength, as expected for a highly-energetic status of the atmosphere., Ministerio de Asuntos Económicos y Transformación Digital y Universidad Complutense de Madrid (projects: (PID2019-105306RB-I00 (IBER - CANES), CGL2016-78702 (SAFEFLIGHT), PCIN-2016-080 and FEI-EU-17-16), Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

A critical problem derived from airport operations is the environmental impact of runoff water. Airport runoff includes a complex mixture of pollutants, e.g., from deicing agents, that may affect negatively natural water bodies. This study assesses the spatial and temporal aquatic ecotoxicity of runoff water and possible aeroplane drift in a German airport. Over winter 2012–2013, from November to May, water samples were collected within the airport and surrounding area. These samples were analyzed using traditional physicochemical analysis and biotests with two aquatic organisms from different trophic levels, Lemna gibba and Aliivibrio fischeri. Overall, the samples examined in this study were relatively non-toxic to the tested organisms. The physicochemical parameters were mainly influenced by the sampling period being higher in colder months. In contrast, the ecotoxicity was influenced by the sampling site. For sites within the airport, a high correlation between the physicochemical parameters (EC and TOC) and toxicity in L. gibba was found. These correlations were not evident in samples taken outside the airport or when A. fischeri was used as a bioindicator. However, a pronounced seasonality has been observed, linked to the coldest months with average inhibition values of 50% in L. gibba and 25% in A. fischeri, particularly in January. Both biotests yielded differing results; therefore, more biotests should be included. However, L. gibba showed a good response with this type of water samples to be included in future studies together with detailed chemical analysis. The present study provides data to assess the potential ecotoxicological effects of airport runoff affected by winter operations.