Pembrolizumab in combination with tocilizumab in high-risk hospitalized patients with COVID-19 (COPERNICO): A randomized proof-of-concept phase II study.

OBJECTIVES: Severe COVID-19 is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated interleukin 6. Pembrolizumab (P; immune-activating anti-programmed cell death-1 antibody) plus tocilizumab (TCZ; anti- interleukin 6 receptor antibody) might interrupt the hyperinflammation and restore cellular immunocompetence. We assessed the efficacy and safety of P + TCZ + standard of care (SOC) in high-risk, hospitalized patients with COVID-19 pneumonia without mechanical ventilation. METHODS: Randomized, controlled, open-label, phase II trial in patients with severe SARS-CoV-2 infection to assess the hospitalization period to discharge. RESULTS: A total of 12 patients were randomized (P + TCZ + SOC, n = 7; SOC, n = 5). Nine (75%) were males, with a median age of 68 (41-79) years. The median time to discharge for P + TCZ + SOC and SOC was 10 and 47.5 days (P = 0.03), with zero (n = 1 patient had P-related grade 5 myositis) and two COVID-19-related deaths, respectively. CONCLUSION: The addition of P and TCZ to SOC reduced the hospitalization period, with higher and faster discharges without sequelae than SOC alone.

A comparative analysis of health surveillance strategies for administrative video display terminal employees.

BACKGROUND: The objective of this study was to develop a strategy to optimize medical health surveillance protocols for administrative employees using video display terminals (VDTs). A total of 2453 medical examinations were analysed for VDT users in various sectors. From these data, using Bayesian statistics we inferred which factors were most relevant to medical diagnosis of the main disorders affecting VDT users. This information was used to build an influence diagram to evaluate the time and monetary costs associated with each diagnostic test and define an optimal protocol strategy based on occupational risks. RESULTS: Musculoskeletal and ophthalmological diseases were identified as the most frequent disorders among VDT users. The Bayesian network inferred age, sleep quality, activity level, smoking and the consumption of alcohol as risk factors. The blood count was the most costly test (5.23 USD/employee) and the second most costly test in time terms (4 min/employee), yet is a diagnostic test that has little influence on the medical decision regarding an employee's capacity to perform their job. CONCLUSIONS: Current occupational health surveillance protocols for VDT users may lead to expenditure that is 54% greater than necessary. For many employees and employers, failure to perform a wide range of medical tests for occupational health surveillance purposes is subjectively perceived as a threat to health. Awareness needs to be raised of the appropriate role of different health areas, so as to optimize diagnostic efficiency on the basis of greater flexibility.

Obtaining the sGAG distribution profile in articular cartilage color images.

The articular cartilage tissue is an essential component of joints as it reduces the friction between the two bones. Its load-bearing properties depend mostly on proteoglycan distribution, which can be analyzed through the study of the presence of sulfated glycosaminoglycan (sGAG). Currently, sGAG distribution in articular cartilage is not completely known; it is calculated by means of laboratory tests that imply the inherent inaccuracy of a manual procedure. This paper presents an easy-to-use desktop software application for obtaining the sGAG distribution profile in tissue. This app uses color images of stained cartilage tissues taken under a microscope, so researchers at the Trinity Centre for Bioengineering (Dublin, Ireland) can understand the qualitative distribution of sGAG with depth in the studied tissues.

A Bayesian assessment of occupational health surveillance in workers exposed to silica in the energy and construction industry.

Medical records generated during occupational health surveillance processes have large amounts of unexploited information that can help to reduce silica-related health risks and many occupational diseases. The methodology applied in this study consists in analyzing through machine learning techniques a database with 70,000 medical examinations from workers in the energy and construction industry in Spain. First, a general unsupervised Bayesian model is built and node force analysis is used to identify the factors with the greatest impact on the worker's health surveillance process. Second, a predictive Bayesian model is created and mutual information is employed to assess the more relevant factors affecting the medical capability of workers exposed to silica dust. The lung auscultation and the breathing exploration are the two factors that influence the most the medical capability of silica-exposed employees. Probabilistic inference shows a remarkable gender effect, where women present more resilience towards occupational diseases than men showing a higher proportion of normal results in certain key factors, such as body mass index (♀49.73%, ♂25.17%) or spirometry (♀53.73%, ♂48.91%). Finally, environmental conditions demonstrate to have a major influence on spatial variability of occupational diseases. The design of health prevention programs based on geographical variations can be crucial to the attainment of an ongoing and sustained healthier workforce with a reduction in the number of chronic workplace illnesses.

A Case of Miller Fisher Syndrome and Literature Review.

Miller Fisher syndrome (MFS)  was first recognized by James Collier in 1932 as a clinical triad of ataxia, areflexia, and ophthalmoplegia. Later, it was described in 1956 by Charles Miller Fisher as a possible variant of Guillain-Barré syndrome (GBS). Here, we write a case of a patient with atypical presentation of this clinical triad as the patient presented with double vision initially due to unilateral ocular involvement that progressed to bilateral ophthalmoplegia. He developed weakness of the lower extremities and areflexia subsequently. A diagnosis of MFS was made due to the clinical presentation and the presence of albuminocytologic dissociation in the cerebrospinal fluid (CSF) along with normal results of brain imaging and blood workup. The patient received intravenous immune globulin (IVIG), and his symptoms improved. The initial diagnosis of MFS is based on the clinical presentation and is confirmed by cerebral spinal fluid analysis and clinical neurophysiology studies. This case which emphasizes the knowledge of a rare syndrome can help narrow down the differentials to act promptly and appropriately manage such patients.

Neural networks applied to discriminate botanical origin of honeys.

The aim of this work is develop a tool based on neural networks to predict the botanical origin of honeys using physical and chemical parameters. The managed database consists of 49 honey samples of 2 different classes: monofloral (almond, holm oak, sweet chestnut, eucalyptus, orange, rosemary, lavender, strawberry trees, thyme, heather, sunflower) and multifloral. The moisture content, electrical conductivity, water activity, ashes content, pH, free acidity, colorimetric coordinates in CIELAB space (L(∗), a(∗), b(∗)) and total phenols content of the honey samples were evaluated. Those properties were considered as input variables of the predictive model. The neural network is optimised through several tests with different numbers of neurons in the hidden layer and also with different input variables. The reduced error rates (5%) allow us to conclude that the botanical origin of honey can be reliably and quickly known from the colorimetric information and the electrical conductivity of honey.

Application of a hybrid 3D-2D laser scanning system to the characterization of slate slabs.

Dimensional control based on 3D laser scanning techniques is widely used in practice. We describe the application of a hybrid 3D-2D laser scanning system to the characterization of slate slabs with structural defects that are difficult for the human eye to characterize objectively. Our study is based on automating the process using a 3D laser scanner and a 2D camera. Our results demonstrate that the application of this hybrid system optimally characterizes slate slabs in terms of the defects described by the Spanish UNE-EN 12326-1 standard.

Learning machines applied to potential forest distribution.

The clearing of forests to obtain land for pasture and agriculture and the replacement of autochthonous species by other faster-growing varieties of trees for timber have both led to the loss of vast areas of forest worldwide. At present, many developed countries are attempting to reverse these effects, establishing policies for the restoration of older woodland systems. Reforestation is a complex matter, planned and carried out by experts who need objective information regarding the type of forest that can be sustained in each area. This information is obtained by drawing up feasibility models constructed using statistical methods that make use of the information provided by morphological and environmental variables (height, gradient, rainfall, etc.) that partially condition the presence or absence of a specific kind of forestation in an area. The aim of this work is to construct a set of feasibility models for woodland located in the basin of the River Liébana (NW Spain), to serve as a support tool for the experts entrusted with carrying out the reforestation project. The techniques used are multilayer perceptron neural networks and support vector machines. Their results will be compared to the results obtained by traditional techniques (such as discriminant analysis and logistic regression) by measuring the degree of fit between each model and the existing distribution of woodlands. The interpretation and problems of the feasibility models are commented on in the Discussion section.

Efecto de una beta lactama de 1.5 benzodiazepina sobre el sueño / Effect of a beta lactame of 1.5 benzodiacepine upon sleep

Existen numerosas substancias, de estructura química diversa que han sido utilizadas como inductoras de sueño. Sin embargo, debido a que producen efectos colaterales indeseables, constantemente son substituidas por fármacos de reciente creación. Este trabajo se llevó a cabo con el propósito de analizar el efecto sobre el sueño de una beta lactama de 1.5 benzodiazepina, administrada intraperitonealmente (0.9 mg/kg) a ratas wistar. Los resultados indican que esta substancia incrementa de manera significativa, tanto al sueño lento como al paradójico a expensas de la vigilia. La lactancia de la primera fase de sueño paradójico, se prolonga significativamente. Se concluye que esta substancia facilita la presencia de sueño, manifestándose su acción durante un período relativamente largo

Efecto de un derivado de la 1,5 benzodiazepina sobre el sueño / Effect of a derivative of 1,5 benzodiazepine upon the sleep cycle

El propósito de este trabajo fue analizar el efecto de un derivado de la benzodiazepina sobre el ciclo vigilia-sueño, que no había sido estudiado. Para este propósito, se le administraron a ratas Wistar 0.9 mg/kg de un derivado clorado de la beta lactama de 1,5 benzodiazepina por vía intraperitoneal, analizando su acción mediante diez horas de registro poligráfico contínuo. Los resultados muestran que esta substancia disminuye el estado de vigilia e incrementan ligeramente el sueño lento y, de manera estadísticamente significativa (p<0.05), el sueño paradójico. Asimismo, la latencia de la primera fase de sueño paradójico se reduce de manera importante. Estos hallazgos indican que la substancia, analizada bajo las condiciones experimentales descritas, facilita la inducción y el mantenimiento del sueño

Actividad molusquicida del piquerol A aislado de piqueria trinervia (compositae) sobre ocho especies de caracoles pulmonados / The molluscicide activity of piquerol A isolated from Piqueria trinervia (Compositae) against 8 species of pulmonate suails

De las partes aéreas de la planta Piqueria trinervia (Compositae) colectada en diveresas áereas de México, se aisló el Piquerol A. Este compuesto se probó como agente molusquicida contra ocho especies de caracoles pulmonados: Fossaria (Fossaria) humilis, F. (Bakerilymnae) sp., Pseudosuccinea columella, Stagnicola attenuata, de México; F. (B.) cubensis y Physacubensis, de Cuba; P. Columella y Biomphalaria glabrata, de Brasil; B glabrata, de Puerto Rico; S. elodes, de Estados Unidos. Se utilizaron tres concentraciones 50, 25 y 5 ppm para cada una de las especies y 2 períodos de exposición, 6 y 24 horas, a 20-22 -C. En 50 ppm, después de 6 horas, y 25 ppm, después de 24 horas los ejemplares de todas las especies murieron. En 5 ppm después de 24 horas, se observaron mortalidades de 60 a 100%. En ningún caso se observó recuperación después de la exposición por 24 horas. El piquerol A es un terpeno biodegradable que presenta otras actividades biológicas. No se han hecho pruebas de toxicidad en otros animales ni pruebas de campo. Sin embargo, es una substacia con alto potencial de uso como molusquicida en zonas de transmisión focal. Es la primera que en México se hacen estudios sistemáticos sobre molusquicidas de origen vegetal

Determinación de algunos parámetros para la producción doméstica de tibicos / Determination of some parameters for the household production of tibicos

Con el objeto de obtener alimentos no convencionales para humanos y animales domésticos, se determinaron las mejores condiciones de cultivo de los tibicos (asociaciones simbióticas de bacterias y levaduras) para producir, en forma doméstica, el mayor rendimento de biomosa a partir de nueve distintos sustratos azucarados de relativo bajo costo, seis consistentes en productos y subproductos de la industria azucarera (piloncillo, melaza, melado, mascabado, azúcar morena y azúcar blanca) y el jugo de betadel, tuna y piña. Se utilizaron diferentes concentraciones de cada sustrato, así como varias temperaturas y tiempos de incubacion. La biomasa de tibicos se midió por peso húmedo drenado (g/100 ml); la tasa específica de crecimiento se calculó en g/hora. El valor más alto en la producción de tibicos (78.8g/100 ml) se obtuvo con 50 g de piloncillo en el medio de cultivo, 29-C y 72 horas de incubación; no obstante, la mayor productividad de biomasa (1.9 g/hora) se obtuvo en el mismo medio a las 24 horas de incubación a 29-C. El segundo mejor sustato fue la melaza, y aunque con ella se produce menos biomasa, es más barato producir 1 g de tibicos utilizando melaza en lugar de piloncillo, cuando se calcula el costo de producción. En el trabajo se comentan las ventajas que ofrece el cultivo de los tibicos en condiciones caseras, sencillas y de bajo costo