Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Coronavirus pandemic: An opportunity to study the anthropogenic impact on micro-climate conditions and CaCO3 crystal morphology in the Nerja Cave (SE Spain).

Following the declaration of the COVID-19 pandemic, the Spanish Government restricted non-essential movements of all citizens and closed all public spaces, such as the Nerja Cave, until May 31, 2020. This particular condition of the closure of the cave provided a unique opportunity to study the micro-climate conditions and carbonate precipitation in this tourist cave without the presence of visitors. Our results show the significant effect of visitors on the air isotopic signature of the cave and on the genesis of the extensive dissolution features affecting the carbonate crystals formed in the tourist sector of the cave, alerting us to the possible corrosion of the speleothems located there. The movement of visitors within the cave also favours the mobilisation of aerial fungi and bacterial spores and their subsequent sedimentation simultaneously with the abiotic precipitation of carbonates from the drip water. The traces of these biotic elements could be the origin of the micro-perforations previously described in the carbonate crystals formed in the tourist galleries of the cave, but they are subsequently enlarged due to abiotic dissolution of the carbonates through these weaker zones.

Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response.

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response.

Response to Monoclonal Antibodies in Asthma: Definitions, Potential Reasons for Failure, and Therapeutic Options for Suboptimal Response

Real-life data reveal that more than half of severe asthma patients treated with monoclonal antibodies (mAbs) do not achieve a complete response. Response to mAbs must be assessed holistically, considering all the clinically meaningful therapeutic goals, not only reduction of exacerbations and oral corticosteroids. There are 2 different ways of measuring the response to mAbs. One, qualitative, classifies patients according to the degree of disease control they have achieved, without explaining how much a given patient improves relative to the baseline (pre-mAb) clinical situation; the other, quantitative, scores the changes occurring after treatment. Both methods are complementary and essential to making clinical decisions on whether to continue treatment. The various potential causes of suboptimal response to mAbs include incorrect identification of the specific T2 pathways, comorbidities that reduce the room for improvement, insufficient dose, autoimmune phenomena, infections, change in the initial inflammatory endotype, and adverse events. Once a suboptimal response has been confirmed, a well-structured and multifaceted assessment of the potential causes of failure should be performed, with emphasis on the resulting inflammatory process of the airway after mAb therapy and the presence of chronic or recurrent infection. This investigation should guide the decision on the best therapeutic approach. The present review aims to help clinicians gain insights into how to measure response to mAbs and proceed in cases of suboptimal response (AU)

Los estudios clínicos en vida real revelan que más de la mitad de los pacientes con asma grave, tratados con anticuerpos monoclonales (mAb), no logran una respuesta completa. La respuesta a los mAbs debe evaluarse de manera integral, considerando todos los objetivos terapéuticos clínicamente significativos y no solo las exacerbaciones o la reducción de corticosteroides orales. Existen dos formas diferentes de medir la respuesta a los mAbs: una, cualitativa, que clasifica a los pacientes según el grado de control de la enfermedad que han logrado, sin explicar cuánto mejora un determinado paciente con respecto a su situación clínica basal (pre-mAb); y la otra, cuantitativa, la cual puntúa los cambios ocurridos después del tratamiento. Ambos métodos son complementarios y claramente esenciales a la hora de tomar decisiones clínicas sobre la continuación del tratamiento con estos fármacos biológicos. Se han descrito varias causas posibles de respuesta subóptima a los mAbs que son: la identificación incorrecta de las vías T2 específicas, las comorbilidades que reducen el margen de mejora, una dosis insuficiente, fenómenos autoinmunes, infecciones, cambio del endotipo inflamatorio inicial y la aparición de efectos adversos. na vez que se ha confirmado una respuesta subóptima, se debe realizar una evaluación bien estructurada y polifacética de estas posibles causas del fracaso, considerando, en particular, el proceso inflamatorio residual de las vías respiratorias tras la terapia con mAb y la presencia de infecciones crónicas o recurrentes. Esta evaluación es la que debe guiar las decisiones sobre el mejor enfoque terapéutico. Esta revisión tiene como objetivo ayudar a los clínicos a obtener un conocimiento más profundo sobre cómo medir la respuesta a los mAbs y cómo proceder con los pacientes que presenten una respuesta subóptima (AU)

Clusters formation and fragmentation of nitromethane at 266 nm.

We carry out experiments on the fragmentation of nitromethane by multiphoton absorption at the wavelength 266 nm. This was conducted in a reflectron (Jordan), modified in the laboratory. Due to the large number of fragments, special care has been taken into the calibration of the system, in the simultaneity between the laser pulse and the sample, and the associated electronics to ensure that produced fragment spectra arise from the interaction laser-sample. We emphasize the next aspects of the method:•Simple design for introducing a gas sample at laser interaction region to facilitate the cluster formation•Astonishing number of fragments produced by multiphoton absorption.

Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

Valoración de bronquiectasias en pacientes con asma / No disponible

Introducción: Las bronquiectasias (BQ) son la consecuencia final de muchas enfermedades, entre las que se encuentra el asma, sin embargo han sido poco estudiadas. El objetivo principal de este estudio fue evaluar la presencia de BQ mediante una tomografía computarizada de alta resolución (TCAR) en un subgrupo de pacientes con asma mediante el sistema de clasificación de Bhalla. Asimismo, se comparó si existían diferencias clínicas entre los asmáticos que presentaban o no BQ y si estas se relacionaban con las puntuaciones obtenidas en la escala de Bhalla modificada. Material y métodos: Una TCAR pulmonar se realizó a pacientes con asma, durante un periodo de reclutamiento de 2 años, que cumplían las siguientes condiciones: tres o más exacerbaciones respiratorias al año, historia de expectoración habitual o hemoptoica en alguna ocasión, o asma de larga evolución. Los escáneres fueron evaluados por 2 radiólogos siguiendo la puntuación de Bhalla modificada. Resultados: Se observaron BQ en 48 pacientes de los 65 estudios realizados; el 88% de las BQ fueron cilíndricas y el 62% bilaterales, siendo los lóbulos más afectos los lóbulos inferiores y el lóbulo medio. En todos los enfermos que padecían reflujo gastroesofágico (RGE) se evidenciaron BQ. Los enfermos con BQ mostraron peor FVC (p=0,04) y FEV1 (p=0,05) y mayor frecuencia de rinitis. La puntuación total obtenida por la puntuación de Bhalla modificada se relacionó con la media del porcentaje del valor FEV1/FVC (p=0,01), con el número de exacerbaciones (p=0,01), y con la presencia de colonización bacteriana (p=0,001). Conclusiones: Una alta proporción de pacientes asmáticos de control difícil muestran BQ, que suelen ser cilíndricas y bilaterales. Los enfermos con BQ presentan peor función pulmonar. La puntuación total mediante el sistema de Bhalla se relaciona con la presencia de colonización bacteriana y con el número de exacerbaciones

Introduction: Bronchiectasis (BQ) are the final consequence of many diseases, including asthma is, however this has been inconsiderate. The main objective was to evaluate the presence of BQ by high resolution computerized tomography (HRCT) in a subgroup of patients with asthma using a modified Bhalla score. We compared also whether there were clinical differences between asthmatics who presented or not BQ and clinical variables were associated with modified Bhalla scores. Material and methods: Pulmonary HRCT was performed in patients with asthma during a recruitment period of 2 years, who had the following conditions: three or more respiratory exacerbations per year history of coughing or hemoptysis usual on occasion, asthma longstanding and images suggestive of BQ in the chest radiograph. The HRCT were evaluated by 2 radiologists according to the modified Bhalla score. Results: We observed 48 patients with BQ in 65 studies, 88% were cylindrical and bilateral in 62%. The more affected were the lower and middle lobes. All patients suffering from gastroesophageal reflux had evident BQ. Patients with BQ showed worse FEV1 (p = 0.04), FVC (p=0.05) and rhinitis more often. The total modified Bhalla score was related to the average percentage of FEV1/FVC value (p=0.01), the number of exacerbations (p = 0.01), and the presence of bacterial colonization (p = 0.01). Conclusions: A high proportion of patients with difficult asthma clinic have BQ. Usually these BQ are bilateral and cylindrical and the patients with BQ present worse respiratory functional state. Bhalla total score correlated with the presence of bacterial colonization and the number of exacerbations

Molecular epidemiology of severe respiratory disease by human rhinoviruses and enteroviruses at a tertiary paediatric hospital in Barcelona, Spain.

In order to describe the molecular epidemiology of human rhinovirus (HRV) and enterovirus (EV) infection in severely ill children, we studied all episodes of bronchospasm/bronchopneumonia in 6-month-old to 18-year-old patients from January 2010 to May 2012 who required mechanical ventilation. HRV/EVs were detected in 55 (57.3%) of 96 patients, of which 50 (91%) were HRV (HRV-A, 16; HRV-B, 1; HRV-C, 18) and 5 (9%) were EVs (EV-D68, 3). No significant differences in epidemiologic and clinical characteristics were found between different types. In six of the 13 patients who required invasive mechanical ventilation, HRV was the only pathogen detected.

Male-specific Y-linked transgene markers to enhance biologically-based control of the Mexican fruit fly, Anastrepha ludens (Diptera: Tephritidae).

BACKGROUND: Reliable marking systems are critical to the prospective field release of transgenic insect strains. This is to unambiguously distinguish released insects from wild insects in the field that are collected in field traps, and tissue-specific markers, such as those that are sperm-specific, have particular uses such as identifying wild females that have mated with released males. For tephritid fruit flies such as the Mexican fruit fly, Anastrepha ludens, polyubiquitin-regulated fluorescent protein body markers allow transgenic fly identification, and fluorescent protein genes regulated by the spermatocyte-specific ß2-tubulin promoter effectively mark sperm. For sterile male release programs, both marking systems can be made male-specific by linkage to the Y chromosome. RESULTS: An A. ludens wild type strain was genetically transformed with a piggyBac vector, pBXL{PUbnlsEGFP, Asß2tub-DsRed.T3}, having the polyubiquitin-regulated EGFP body marker, and the ß2-tubulin-regulated DsRed.T3 sperm-specific marker. Autosomal insertion lines effectively expressed both markers, but a single Y-linked insertion (YEGFP strain) expressed only PUbnlsEGFP. This insertion was remobilized by transposase helper injection, which resulted in three new autosomal insertion lines that expressed both markers. This indicated that the original Y-linked Asß2tub-DsRed.T3 marker was functional, but specifically suppressed on the Y chromosome. The PUbnlsEGFP marker remained effective however, and the YEGFP strain was used to create a sexing strain by translocating the wild type allele of the black pupae (bp+) gene onto the Y, which was then introduced into the bp- mutant strain. This allows the mechanical separation of mutant female black pupae from male brown pupae, that can be identified as adults by EGFP fluorescence. CONCLUSIONS: A Y-linked insertion of the pBXL{PUbnlsEGFP, Asß2tub-DsRed.T3} transformation vector in A. ludens resulted in male-specific expression of the EGFP fluorescent protein marker, and was integrated into a black pupae translocation sexing strain (T(YEGFP/bp+), allowing the identification of male adults when used in sterile male release programs for population control. A unique observation was that expression of the Asß2tub-DsRed.T3 sperm-specific marker, which was functional in autosomal insertions, was specifically suppressed in the Y-linked insertion. This may relate to the Y chromosomal regulation of male-specific germ-line genes in Drosophila.

Microsystem-assisted synthesis of carbon dots with fluorescent and colorimetric properties for pH detection.

The present paper describes the use of a microfluidic system to synthesize carbon dots (Cdots) and their use as optical pH sensors. The synthesis is based on the thermal decomposition of ascorbic acid in dimethyl sulfoxide. The proposed microsystem is composed of a fluidic and a thermal platform, which enable proper control of synthesis variables. Uniform and monodispersed 3.3 nm-sized Cdots have been synthesized, the optical characterization of which showed their down/upconversion luminescence and colorimetric properties. The obtained Cdots have been used for pH detection with down and upconverison fluorescent properties as excitation sources. The naked eye or a photographic digital camera has also been implemented as detection systems with the hue parameter showing a linear pH range from 3.5 to 10.2. On the other hand, experiments on the cytotoxicity and permeability of the Cdots on human embryonic kidney cells revealed their adsorption on cells without causing any impact on the cellular morphology.