Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.

BACKGROUND: Potential differences in organ preservation between total neoadjuvant therapy (TNT) regimens integrating long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT) in rectal cancer remain undefined. PATIENTS AND METHODS: This natural experiment arose from a policy change in response to the COVID-19 pandemic during which our institution switched from uniformly treating patients with LCCRT to mandating that all patients be treated with SCRT. Our study includes 323 locally advanced rectal adenocarcinoma patients treated with LCCRT-based or SCRT-based TNT from January 2018 to January 2021. Patients who achieved clinical complete response were offered organ preservation with watch-and-wait (WW) management. The primary outcome was 2-year organ preservation. Additional outcomes included local regrowth, distant recurrence, disease-free survival (DFS), and overall survival (OS). RESULTS: Patient and tumor characteristics were similar between LCCRT (n = 247) and SCRT (n = 76) cohorts. Median follow-up was 31 months. Similar clinical complete response rates were observed following LCCRT and SCRT (44.5% versus 43.4%). Two-year organ preservation was 40% [95% confidence interval (CI) 34% to 46%] and 31% (95% CI 22% to 44%) among all patients treated with LCCRT and SCRT, respectively. In patients managed with WW, LCCRT resulted in higher 2-year organ preservation (89% LCCRT, 95% CI 83% to 95% versus 70% SCRT, 95% CI 55% to 90%; P = 0.005) and lower 2-year local regrowth (19% LCCRT, 95% CI 11% to 26% versus 36% SCRT, 95% CI 16% to 52%; P = 0.072) compared with SCRT. The 2-year distant recurrence (10% versus 6%), DFS (90% versus 90%), and OS (99% versus 100%) were similar between WW patients treated with LCCRT and SCRT, respectively. CONCLUSIONS: While WW eligibility was similar between cohorts, WW patients treated with LCCRT had higher 2-year organ preservation and lower local regrowth than those treated with SCRT, yet similar DFS and OS. These data support induction LCCRT followed by consolidation chemotherapy as the preferred TNT regimen for patients with locally advanced rectal cancer pursuing organ preservation.

Changes in the epidemiology of kidney replacement therapy across Europe in 2020-the first year of the COVID-19 pandemic: an ERA Registry study.

BACKGROUND: In 2020, the coronavirus disease 2019 (COVID-19) pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe. METHODS: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Changes occurring during the first and second waves of the pandemic were also explored. RESULTS: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%) and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%) but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and was greatest for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decrease. In dialysis patients, mortality increased by 11.4% and was highest in those 65-74 years of age (16.1%), in those with diabetes as the primary renal disease (15.1%) and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N = 317 787) resembled that of 2019 (N = 317 077). CONCLUSION: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT and prevalence of KRT in Europe with variations across countries.

Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

The African introgression of Murciano Granadina goats has a Moroccan origin and displays remarkable levels of inter-individual variability.

There is evidence that Murciano Granadina (MG), the most important caprine dairy breed in Spain, has been introgressed by African goats, but the precise geographic origin of such introgression has not been identified yet. Moreover, an accurate estimate of the magnitude of this African introgression is lacking, since current estimates are based on small numbers of sampled individuals. The aim of our work was to tackle these two issues by genotyping 500 MG goats with the Goat SNP50 BeadChip and comparing their genotypes with those of reference populations from Spain (Bermeya), France (Saanen), Morocco (Barcha, Draa, Ghazalia, Noire de Atlas, Nord, Moroccan), Egypt (Barki, Oasis, Saidi), Algeria (Arabia, Makatia, M'Zabite, Kabyle), Tunisia (Tunisian native breeds) and Sudan (Desert, Nilotic, Taggar). The population of 500 MG goats was subdivided into 10 datasets of 50 individuals to ensure that sample sizes of the target (MG) and reference populations are balanced. Performance of an unsupervised ADMIXTURE analysis demonstrated that MG goats have a North African ancestry, with an average proportion of 4.4 ± 2.3%. Next, we did a supervised ADMIXTURE analysis that revealed that the Moroccan genetic component reaches a proportion of 4.01 ± 3.9% in MG goats, while the Algerian (0.001 ± 0.001%), Egyptian (0.2 ± 0.1%), Sudanese (0.1 ± 0.1%) and Tunisian (0.3 ± 0.4%) components are present in extremely small proportions. The historical circumstances of this introgression event are currently unknown, but several plausible scenarios are outlined. Moreover, our results show considerable inter-individual heterogeneity regarding the magnitude of the Moroccan introgression of MG goats (0%- 12% depending on the MG data set under analysis). This result implies that reliable estimates about the introgression of autochthonous livestock by exotic breeds can only be obtained by extensively sampling target populations.

Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.

Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Contribution of halloysite as nanotubular clay mineral on mechanism and adsorption rate of Cd(II) onto nanocomposites alginate-halloysite.

In this work nanocomposites based on alginate (Alg) and halloysite as a nanotubular clay (Hy) were developed. Characterization techniques reveal that Hy/Alg nanocomposites are cation exchangers with predominantly negative charge density and good thermal stability. The adsorption equilibrium of Cd(II) in aqueous solution onto Hy/Alg nanocomposites revealed that by increasing the mass of halloysite in the nanocomposite, the adsorption capacity diminished significantly due to the halloysite-alginate interactions. Maximum adsorption capacities of 8, 65, 88, and 132 mg/g of Cd(II) were obtained for samples Hy, Hy/Alg 50%, Hy/Alg 95%, and Alg, respectively. In addition, the adsorption equilibrium of Cd(II) on the Hy/Alg bionanocomposites was affected by the pH and temperature of the solution, demonstrating the presence of electrostatic interactions during adsorption and that this is an exothermic process. The controlling mechanism of adsorption was cation exchange influenced by electrostatic forces. The Cd(II) adsorption rate studies were interpreted by the diffusion-permeation model and reveal that the presence of Hy in the structure of the nanocomposites enhances the permeation coefficient, that is, the adsorption rate was increased. The values of the permeation coefficient varied from 1.95 × 10-7 to 8.50 × 10-7 cm2/s for Hy/Alg 50% and from 1.70 × 10-7 to 3.55 × 10-7 cm2/s for Hy/Alg 95%.

Enantiosensitive growth dynamics of chiral molecules on ferromagnetic substrates and the origin of the CISS effect.

The recent demonstration of the existence of an intimate relationship between the chiral structure of some materials and the spin polarization of electrons transmitted through them, what has been called the chirality-induced spin selectivity (CISS) effect, is sparking interest in many related phenomena. One of the most notorious is the possibility of using magnetic materials to apply enantioselective interactions on chiral molecules and chemical reactions involving them. In this work, x-ray photoelectron spectroscopy has been used to characterize the adsorption and growth kinetics of enantiopure organic molecules on magnetic (Co) and non-magnetic (Cu) substrates. While on these latter, no significant enantiosensitive effects are found, on spin-polarized, in-plane magnetized Co surfaces, the two enantiomers have been found to deposit differently. The observed effects have been interpreted as the result of one of the enantiomers being adsorbed in a transient, weakly bound physisorbed-like state with higher mobility due to limited, spin-selective charge transfer between it and the substrate. The study of these phenomena can provide insight into the fundamental mechanisms responsible for the CISS effect.

Evolution of Guidelines for the Management of Hereditary Angioedema due to C1 Inhibitor Deficiency.

Hereditary angioedema (HAE) is a severe and disabling condition characterized by recurrent episodes of subcutaneous or mucosal swelling in the skin and respiratory and gastrointestinal tracts. HAE due to C1-esterase inhibitor deficiency (C1-INH-HAE) is the most prevalent subtype. The present Iberian study compared C1-INH-HAE treatment guidelines published between 2010 and 2022 to identify the main differences in therapeutic approaches for on-demand treatment and short- and long-term prophylaxis (LTP). HAE guidelines evolved with the availability of new treatments and with a change in the management paradigm towards an individualized, patient-centered approach, where quality of life (QOL) is central. A parallel trend was observed towards increasingly frequent home-based treatment, which potentially facilitates timely interventions, provides greater flexibility and convenience, and is associated with increased QOL, enabling patients to lead more normal lives. Most innovations over the years were made for LTP, together with the advent of new therapies and awareness of patients' needs. Several prophylactic therapies with a high level of evidence became available, although formal head-to-head comparisons are lacking. The treatment goals became more ambitious, ranging from a reduction in the frequency, severity, and duration of attacks to achieving total disease control and normalization of patients' lives. The document also addresses relevant items such as changes in terminology (eg, the introduction of designations as "first-line") and the introduction of patient-reported outcome measures to assess patients' perceptions of their self-experienced QOL and well-being. Unmet needs in the management of C1-INH-HAE are identified.

Electronic device or regulated tobacco product? Learning from the diffusion of heated tobacco products in Spain.

OBJECTIVES: Tobacco companies have introduced heated tobacco product (HTP) in many countries and marketed it on the grounds that it is a less harmful alternative to health. However, tobacco companies have been widely criticized for taking advantage of a loophole that allows electronic devices to circumvent regulations limiting tobacco advertising. This work aims to determine whether HTPs respected the rules that regulate tobacco advertising when it was introduced in Spain. STUDY DESIGN: This is an observational epidemiological study. METHODS: Using monthly time series data from September 2016 to June 2020, we analyzed whether the adoption of HTPs has followed the same behavior patterns as other brands that were introduced under the same conditions of use. The Bass model is used to analyze the diffusion of HTPs, and 30 other traditional cigarette brands introduced under the same conditions as this HTPs. RESULTS: The adoption of HTPs in Spain has been like that of brands of slim cigarettes that are mistakenly considered to be healthier than traditional cigarettes. The results indicate that the use of HTPs has spread in the same way as additive-free and ultra-slim cigarette brands. CONCLUSIONS: Policymakers should keep in mind that laws should restrict any marketing of tobacco products that promotes positive connotations between tobacco use and being healthy. If manufacturers are allowed to classify a category and/or brand of tobacco products as less harmful to health, the imitation effect is very high, leading to the proliferation of smoking.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

Spanish Academy of Dermatology and Venereology (AEDV) expert recommendations for the management of sexual transmitted parasitosis. Scabies, and pediculosis pubis. / Recomendaciones de expertos de la Academia Española de Dermatología (AEDV) para el manejo de las ectoparasitosis de transmisión sexual. Escabiosis y pediculosis púbica.

Sexually transmitted infections are communicable diseases where the pathogen is transmitted through sexual contact. The Sexually Transmitted Infections Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) is engaged in the drafting of documents to guide dermatologists and health care personnel who treat Spanish patients with these infections. This document analyzes the epidemiological, clinical, therapeutic, and control characteristics of 2 sexually transmitted parasitosis: scabies due to Sarcoptes scabiei var. hominis, and pubic pediculosis due to Phthirus pubis. Both parasitoses share a sort of mixed spread through sexual and community transmission regardless of the route through which the infection was initially acquired. This specific feature creates particularities in the management and control of the infestation.

Efficacy of bio- and neurofeedback for depression: a meta-analysis.

BACKGROUND: For many years, biofeedback and neurofeedback have been implemented in the treatment of depression. However, the effectiveness of these techniques on depressive symptomatology is still controversial. Hence, we conducted a meta-analysis of studies extracted from PubMed, Scopus, Web of Science and Embase. METHODS: Two different strings were considered for each of the two objectives of the study: A first group comprising studies patients with major depressive disorder (MDD) and a second group including studies targeting depressive symptomatology reduction in other mental or medical conditions. RESULTS: In the first group of studies including patients with MDD, the within-group analyses yielded an effect size of Hedges' g = 0.717, while the between-group analysis an effect size of Hedges' g = 1.050. Moderator analyses indicate that treatment efficacy is only significant when accounting for experimental design, in favor of randomized controlled trials (RCTs) in comparison to non RCTs, whereas the type of neurofeedback, trial design, year of publication, number of sessions, age, sex and quality of study did not influence treatment efficacy. In the second group of studies, a small but significant effect between groups was found (Hedges' g = 0.303) in favor of bio- and neurofeedback against control groups. Moderator analyses revealed that treatment efficacy was not moderated by any of the sociodemographic and clinical variables. CONCLUSIONS: Heart rate variability (HRV) biofeedback and neurofeedback are associated with a reduction in self-reported depression. Despite the fact that the field has still a large room for improvement in terms of research quality, the results presented in this study suggests that both modalities may become relevant complementary strategies for the treatment of MDD and depressive symptomatology in the coming years.

Effect of the topical administration of corticosteroids and tuberculin pre-sensitisation on the diagnosis of tuberculosis in goats.

BACKGROUND: Caprine tuberculosis (TB) is a zoonosis caused by members of the Mycobacterium tuberculosis complex (MTBC). Caprine TB control and eradication programmes have traditionally been based on intradermal tuberculin tests and slaughterhouse surveillance. However, this strategy has limitations in terms of sensitivity and specificity. Different factors may affect the performance of the TB diagnostic tests used in goats and, subsequently, the detection of TB-infected animals. In the present study, the effect of two of the factors that may affect the performance of the techniques used to diagnose TB in goats, the topical administration of corticosteroids and a recent pre-sensitisation with tuberculin, was analysed. METHODS: The animals (n = 151) were distributed into three groups: (1) a group topically treated with corticosteroids 48 h after intradermal tuberculin tests (n = 53); (2) a group pre-sensitised with bovine and avian purified protein derivatives (PPDs) 3 days before the intradermal tuberculin test used for TB diagnosis (n = 48); and (3) a control group (n = 50). All the animals were tested using single and comparative intradermal tuberculin (SIT and CIT, respectively) tests, an interferon-gamma release assay (IGRA) and a P22 ELISA. RESULTS: The number of SIT test reactors was significantly lower in the group treated with corticosteroids when compared to the pre-sensitised (p < 0.001) and control (p = 0.036) groups. In contrast, pre-sensitisation with bovine and avian PPDs did not cause a significant reduction in the number of SIT and CIT test reactors compared with the control group. In fact, a higher number of reactors was observed after the prior tuberculin injection in the pre-sensitised group (p > 0.05). No significant effect was observed on IGRA and P22 ELISA due to corticosteroids administration. Nevertheless, a previous PPD injection affected the IGRA performance in some groups. CONCLUSIONS: The application of topical corticosteroid 24 h before reading the SIT and CIT tests can reduce the increase in skin fold thickness and subsequently significantly decrease the number of positive reactors. Corticosteroids used can be detected in hair samples. A previous pre-sensitisation with bovine and avian PPDs does not lead to a significant reduction in the number of intradermal tests reactors. These results are valuable in order to improve diagnosis of caprine TB and detect fraudulent activities in the context of eradication programs.

Efficacy and safety of oral sirolimus for high-flow vascular malformations in real clinical practice.

BACKGROUND: Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. AIM: To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. METHODS: In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. RESULTS: Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. CONCLUSION: Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Effect of clay and guishe-ash as substrate on Lycopersicon esculentum germination and production.

The effect of biomass ash and clay on tomato plants (Lycopersicon esculentum) in greenhouse conditions from germination to production was studied. Biomass ash is a waste obtained from thermal treatment of guishe (a by-product of natural fiber), and clay is collected from local soils. Several trials were performed to assess the influence of the addition of clay and guishe-ash on seeds germination, seedling growth, and production yield. The decrease in the values of these variables was considered an indicator of toxicity. The obtained results showed that based clay/ash materials positively affect germination (average ∼90% and six materials allow obtaining 90%) and seedlings growth (an increase of ∼20% in height and more than 50% in fresh air corpuscular weight). However, applying these materials on the production stage induces minor positive effects on fruit diameter, locule number, pericarp thickness, and the number of seeds per fruit. Also, adverse effects (first harvest yield, number of fruits, fresh mass of ripe fruits, lycopene content) were observed. To valorize biomass ash, its combination with other materials such as clay could be an alternative to improve tomato production.

The concern to attend the growing demand for food has promoted the use of different kinds of materials as enhancers of plant growth and crop productivity. Among the materials that have been applied in crops are the wastes of biomass thermochemical processes, such as biochar and ashes. This work highlights the importance of evaluating the effect of applying a residue (guishe-ash) to a crop before promoting its use.

Deep Learning-Based Feature Extraction of Acoustic Emission Signals for Monitoring Wear of Grinding Wheels.

Tool wear monitoring is a critical issue in advanced manufacturing systems. In the search for sensing devices that can provide information about the grinding process, Acoustic Emission (AE) appears to be a promising technology. The present paper presents a novel deep learning-based proposal for grinding wheel wear status monitoring using an AE sensor. The most relevant finding is the possibility of efficient feature extraction form frequency plots using CNNs. Feature extraction from FFT plots requires sound domain-expert knowledge, and thus we present a new approach to automated feature extraction using a pre-trained CNN. Using the features extracted for different industrial grinding conditions, t-SNE and PCA clustering algorithms were tested for wheel wear state identification. Results are compared for different industrial grinding conditions. The initial state of the wheel, resulting from the dressing operation, is clearly identified for all the experiments carried out. This is a very important finding, since dressing strongly affects operation performance. When grinding parameters produce acute wear of the wheel, the algorithms show very good clustering performance using the features extracted by the CNN. Performance of both t-SNE and PCA was very much the same, thus confirming the excellent efficiency of the pre-trained CNN for automated feature extraction from FFT plots.

Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients.

BACKGROUND: Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600mut melanoma. High plasma concentration of D (PCD) is weakly associated with adverse events (AE). We investigated the relationship between PCD/T and tumour control or AE. METHODS: We analysed PCD/T in patients treated with D+T for metastatic melanoma. We collected data of tumour response (RECIST 1.1) and AE (CTCAE 4.0) blinded to PCD/T results. RESULTS: We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0ng/mL; interquartile range (IQR) [4-945]) and of PCT (median: 8.6ng/mL; IQR [5-39]) was observed. We found a weak relationship between PCD and progression-free survival, taking follow-up time into account (hazard ratio 0.991; 95%CI, 0.981 to 1.000; P=0.06). However, no difference was observed between mean PCD/T of progressing patients (n=21; 125±183ng/mL and 9.3±3.6ng/mL, respectively) and responders (complete, partial or stable response) (n=13; 159±225ng/mL, P=0.58 and 10.6±24.4ng/mL, P=0.29, respectively). No significant relationship was found between PCD/T and most common AEs (fever, lymphopenia, CPK increase, and hepatic cytolysis), body mass index, or age. Mean CPT (n=16) was significantly higher for female subjects (n=18; 11.5±4.8ng/mL) than for male subjects (8.8ng/mL±2.9, P=0.01), but no difference was observed between sex and CPD (P=0.32). CONCLUSION: Our study showed a weak relationship between PCD and progression-free survival, but no relationship between PCD/T and AE was found. Monitoring PCD and PCT alone is unlikely to be useful in assessing response to treatment.

COVID-19 in transplant recipients: The Spanish experience.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).