Fast and accurate computation of the Euclidean distance transform in medical imaging analysis software

Se implementó una aplicación utilizando el lenguaje de programación Phyton y las librerías ITK y VTK para un cálculo rápido y preciso de la transformada Euclidiana de distancia. Se compararon dos algoritmos, el propuesto por Saitho y el algoritmo de Danielsson en la versión four-points Sequencial Euclidean distance (4SED). Se evaluó la precisión y la velocidad computacional de ambos algoritmos, encontrando que la versión propuesta por Saitho es más rápida. Se implementó una aplicación de software para el cálculo de la transformada Euclidiana de distancia, incluyendo herramientas para la segmentacion de imágenes de micro-CT de estructuras óseas. A futuro esta aplicación puede ser usada en conjunto con otros software para análisis de imágenes en el procesamiento de estructuras oseasFast and accurate computation of the Euclidean distance map transformation is presented using the python programming language in conjunction with the vtk and itk toolkits. Two algorithms are compared on the basis of their efficiency and computational speed; Saitho algorithm and Danielsson’s four-points Sequential Euclidean Distance (4SED). An algorithm is used to compute a scalar distance map from a 3D data set or volume, which can be used to extract specific distance values. The performance time for the Saitho computation speed was less than the Danielsson’s 4SED computation allowing a faster calculation of the Euclidean distance map. A software analysis application was implemented using the Saitho algorithm for the computation of the scalar distance maps; it also included an underlying segmentation method to allow the computation of Euclidean distance maps on micro-CT images of segmented bone structures. In the future, this application could be used in conjunction with other image processing software applications of bone analysi

Evidence of rapid adaptation integrated into projections of temperature-related excess mortality

Few studies have used empirical evidence of past adaptation to project temperature-related excess mortality under climate change. Here, we assess adaptation in future projections of temperature-related excess mortality by employing evidence of shifting minimum mortality temperatures (MMTs) concurrent with climate warming of recent decades. The study is based on daily non-external mortality and daily mean temperature time-series from 11 Spanish cities covering four decades (1978–2017). It employs distributed lag non-linear models (DLNMs) to describe temperature-mortality associations, and multivariate mixed-effect meta-regression models to derive city- and subperiod-specific MMTs, and subsequently MMT associations with climatic indicators. We use temperature projections for one low- and one high-emission scenario (ssp126, ssp370) derived from five global climate models. Our results show that MMTs have closely tracked mean summer temperatures (MSTs) over time and space, with meta-regression models suggesting that the MMTs increased by 0.73 °C (95%CI: 0.65, 0.80) per 1 °C rise in MST over time, and by 0.84 °C (95%CI: 0.76, 0.92) per 1 °C rise in MST across cities. Future projections, which include adaptation by shifting MMTs according to observed temporal changes, result in 63.5% (95%CI: 50.0, 81.2) lower heat-related excess mortality, 63.7% (95%CI: 30.2, 166.7) higher cold-related excess mortality, and 11.2% (95%CI: −5.5, 39.5) lower total temperature-related excess mortality in the 2090s for ssp370 compared to estimates that do not account for adaptation. For ssp126, assumptions on adaptation have a comparatively small impact on excess mortality estimates. Elucidating the adaptive capacities of societies can motivate strengthened efforts to implement specific adaptation measures directed at reducing heat stress under climate change

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties

VirtualEar: Diseño y construcción de un audiómetro virtual

Se desarrolló un audiómetro virtual en la plataforma de instrumentación virtual Labview 7.1. VirtualEar es un sistema que permite evaluar la capacidad auditiva mediante la realización de una prueba de audiometría aérea con posibilidad de enmascaramiento para detectar la audición cruzada. La audiometría se realiza reproduciendo tonos puros en el intervalo de frecuencias audibles (125Hz-8000Hz) con intensidad de presión sonora (SPL) variable en un rango de 0dB a 110dB. El enmascaramiento consiste en enviar una señal de ruido blanco al oído opuesto del que se está evaluando la capacidad auditiva. Ambas señales se emiten por dos canales separados y conforme se hace la prueba se van detectando los umbrales de mínima presión sonora audible. El audiómetro virtual VirtualEar permite generar y guardar la información en tablas, gráficos y reportes. Además permite manejar archivos de cada paciente e imprimir resultados.A virtual audiometer was developed using the virtual instrumentation platform Labview7.1. VirtualEar is a system that permits the evaluation of the audible capacity of a person, through an audiometric prove by air, with masking, to detect the crossed audition. The audiometry is done producing pure tones in the audible frequency’s range (125Hz-8000Hz) with pressure intensity that varies in a range from 0dB to 100dB. Masking consists on sending a white noise signal to the opposite ear of the one that is being tested. Both signals are emitted through two separate channels, and in that way, the threshold of minimum audible pressure is detected. VirtualEar also permits to generate and save the information in tables, graphics and reports. Furthermore, it’s possible to control each patient’s files and print the results

A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients

Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). KRAS exon-2 status was evaluated centrally, along with NRAS, BRAF mutations, epiregulin, amphiregulin, PTEN and EGFR copy number status, and correlated with efficacy. Sixty-one patients were treated. Among the 46 wild-type RAS patients, the ORR was 15.2% (seven partial responses), with median PFS of 3.8 months (95% CI 2.7-4.3) and median OS of 12.5 months (95% CI 6.7-15.9). Wild-type BRAF patients showed a 13.0% response rate. No significant correlations between response and baseline biomarker expression were identified. Common grade 3-4 adverse events were diarrhoea and rash (18.0% each), hypomagnesaemia and asthenia (8.2% each). The addition of panitumumab to irinotecan as salvage therapy is feasible but has limited activity in irinotecan-refractory metastatic colorectal cancer. No biomarkers predictive of response were identified

Docetaxel-Loaded Nanoparticles Assembled from β-Cyclodextrin/Calixarene Giant Surfactants: Physicochemical Properties and Cytotoxic Effect in Prostate Cancer and Glioblastoma Cells

Giant amphiphiles encompassing a hydrophilic β-cyclodextrin (βCD) component and a hydrophobic calix[4]arene (CA4) module undergo self-assembly in aqueous media to afford core-shell nanospheres or nanocapsules, depending on the nanoprecipitation protocol, with high docetaxel (DTX) loading capacity. The blank and loaded nanoparticles have been fully characterized by dynamic light scattering (DLS), ζ-potential measurements and cryo-transmission electron microscopy (cryo-TEM). The data are compatible with the distribution of the drug between the nanoparticle core and the shell, where it is probably anchored by inclusion of the DTX aromatic moieties in βCD cavities. Indeed, the release kinetics profiles evidenced an initial fast release of the drug, which likely accounts for the fraction hosted on the surface, followed by a slow and sustained release rate, corresponding to diffusion of DTX in the core, which can be finely tuned by modification of the giant amphiphile chemical structure. The ability of the docetaxel-loaded nanoparticles to induce cellular death in different prostate (human LnCap and PC3) and glioblastoma (human U87 and rat C6) cells was also explored. Giant amphiphile-based DTX formulations surpassing or matching the antitumoral activity of the free DTX formulation were identified in all cases with no need to employ any organic co-solvent, thus overcoming the DTX water solubility problems. Moreover, the presence of the βCD shell at the surface of the assemblies is intended to impart stealth properties against serum proteins while permitting nanoparticle surface decoration by supramolecular approaches, paving the way for a new generation of molecularly well-defined antitumoral drug delivery systems with improved specificity and efficiency. Altogether, the results provide a proof of concept of the suitability of the approach based on βCD-CA4 giant amphiphiles to access DTX carriers with tunable properties

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

MEDIDAS PARA LA CONSERVACIÓN DE LA BIODIVERSIDAD DE LOS POLINIZADORES SILVESTRES EN LA PENÍNSULA IBÉRICA

Los científicos y científicas abajo firmantes consideramos muy importante hacer llegar a instituciones, agricultores/as y a la sociedad en general, la necesidad urgente de implementar conjuntamente medidas y cambios que consigan frenar el declive de los polinizadores silvestres ocasionado por la actividad humana. Durante la última década, son múltiples los estudios que alertan de la creciente desaparición de los polinizadores por todo el mundo, en concreto de las abejas silvestres, (Biesmeijer et al. 2006; Potts et al. 2010; Burkle et al. 2013), y de las graves consecuencias que su déficit podría provocar sobre la biodiversidad global (Biesmeijer et al. 2006; Burkle et al. 2013; Lundgren et al. 2016) y sobre la producción agrícola (Aizen y Harder 2009; Garibaldi et al. 2013). No debemos olvidar que la península Ibérica es, por su condición mediterránea y su proximidad al continente africano, uno de los lugares con mayor diversidad de polinizadores de la Unión Europea y, en concreto, una de las zonas con mayor diversidad de abejas del mundo (Michener 2007; Nieto et al. 2014). Hasta el momento, el número de especies de abejas en España presentes en la zona íbero-balear es algo superior a 1.100, cifra a la que cabe añadir algunas especies exclusivas de Portugal más los nuevos hallazgos de los últimos años (Ortiz-Sánchez 2011). Esta gran diversidad de abejas y polinizadores en general está asociada al gran número de especies de plantas con flor presentes en la península Ibérica, alrededor de las 7.000 especies (Aguado Martín et al. 2015). En cuanto al número de mariposas y polillas (lepidópteros) se estima que existen en la península Ibérica unas 5.000 especies (Stefanescu et al. 2018). Más difícil es estimar el número exacto de especies de escarabajos florícolas (coleópteros polinizadores), pero atendiendo a la riqueza de los principales géneros podemos estimar su número en más de 750 (Stefanescu et al. 2018). Somos conscientes de que, a pesar del desarrollo explosivo de los últimos 10 años de la investigación en ecología y gestión de la polinización de los cultivos por insectos silvestres, hoy en día son numerosas las lagunas de conocimiento básico y aplicado sobre el estado de conservación de los insectos polinizadores silvestres. Y es, bajo esta premisa, que presentamos este trabajo de revisión de la literatura científica sobre insectos polinizadores desde principios del siglo XX hasta ahora, cuyo resultado ha quedado plasmado en una lista, no exhaustiva, de los aspectos que consideramos fundamentales para el desarrollo y debate de esta relevante cuestió

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd