Building uncertainty models on top of black-box predictive APIs

With the commoditization of machine learning, more and more off-the-shelf models are available as part of code libraries or cloud services. Typically, data scientists and other users apply these models as ''black boxes'' within larger projects. In the case of regressing a scalar quantity, such APIs typically offer a predict() function, which outputs the estimated target variable (often referred to as y¿ or, in code, y_hat). However, many real-world problems may require some sort of deviation interval or uncertainty score rather than a single point-wise estimate. In other words, a mechanism is needed with which to answer the question ''How confident is the system about that prediction?'' Motivated by the lack of this characteristic in most predictive APIs designed for regression purposes, we propose a method that adds an uncertainty score to every black-box prediction. Since the underlying model is not accessible, and therefore standard Bayesian approaches are not applicable, we adopt an empirical approach and fit an uncertainty model using a labelled dataset (x, y) and the outputs y¿ of the black box. In order to be able to use any predictive system as a black box and adapt to its complex behaviours, we propose three variants of an uncertainty model based on deep networks. The first adds a heteroscedastic noise component to the black-box output, the second predicts the residuals of the black box, and the third performs quantile regression using deep networks. Experiments using real financial data that contain an in-production black-box system and two public datasets (energy forecasting and biology responses) illustrate and quantify how uncertainty scores can be added to black-box outputs

A Novel, Quick, and Reliable Smartphone-Based Method for Serum PSA Quantification: Original Design of a Portable Microfluidic Immunosensor-Based System

We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at -100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL(-1) to 1500 pg mL(-1). The sensitivity was demonstrated by a detection limit of 2 pg mL(-1) and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.Universidad Nacional de San Luis PROICO 22/Q241ANPCyT PICT 2018-04443 PICT-2015-2246 PICT-2015-1575 PICT-2014-1184 PICT-2014-0375 PICT-2018-04443Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) PIP 11220150100004COGENYOCentre for Genomics and Oncological Research: Pfizer-University of GranadaAndalusian Regional Government (Granada, Spain)ISCIII Health Research Institute P17/00989La Caixa FoundationHealth and Family Secretariat of the Andalusian Regional GovernmentSpanish GovernmentH2020-MSCA-IF-2019-89566

Matrix metalloproteinase-10 effectively reduces infarct size in experimental stroke by enhancing fibrinolysis via a thrombin-activatable fibrinolysis inhibitor-mediated mechanism

BACKGROUND: The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown. METHODS AND RESULTS: The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10-null mice (Mmp10(-/-)), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator-induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation-mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in Mmp10(-/-) mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator-treated animals were severely impaired in Mmp10(-/-) mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor-deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect. CONCLUSIONS: A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis

Actividad física, ejercicio y deporte en la lucha contra la obesidad infantil y juvenil

El propósito del presente documento es proponer desde el grupo de expertos en ejercicio físico y salud de EXERNET (Red Española de Investigación en Ejercicio Físico y Salud) una serie de recomendaciones sobre la práctica de la actividad física y deportiva que a nivel individual, familiar e institucional ayuden a prevenir y tratar la obesidad infantil y juvenil, basadas en la evidencia científi ca actual

Influence of the Fukushima Dai-ichi nuclear accident on Spanish environmental radioactivity levels

This paper presents measurements of the effect of the atmospheric radioactive release from the Fukushima Dai-ichi nuclear power station at three sites belonging to the Spanish environmental monitoring system. Measured values varied depending on the locations of the sites in Spain and their respective climatic characteristics. 134Cs, 136Cs, 137Cs, 131I, and 132Te activity concentrations in filter samples were studied and associated levels of 131I fallout were estimated from wet and dry deposition. Particulate aerosol activity concentrations ranges, in μBq/m3, were 1.63–3080 (131I), 2.8–690 (137Cs), 1.3–620 (134Cs) and 3.6–330 (132Te), while the associated 131I fallout was roughly estimated to be less than 20 Bq/m2, Gaseous 131I was also detected and the 131I-gaseous/131I-total ratio increased at the three stations from approximately 0.75 at the end of March to 0.85–0.9 during the first few days of April. Finally, the presence of 131I in some crucial parts of the food chain was also studied. 131I was detected in samples from goat's and cow's milk (maximum levels of 1.11 Bq/L) and in broadleaf plants (maximum level 1.42 Bq/kg).The authors gratefully acknowledge financial support from the Spanish Nuclear Security Council (Consejo de Seguridad Nuclear) within the framework of the Environmental Radiological Surveillance Program which operates in Spain under its control and responsibility.Peer reviewe

Taphonomic and spatial analyses from the Early Pleistocene site of Venta Micena 4 (Orce, Guadix-Baza Basin, southern Spain)

Venta Micena is an area containing several palaeontological sites marking the beginning of the Calabrian stage (Early Pleistocene). The richness of the fossil accumulation including species of Asian, African and European origin, makes Venta Micena a key site for the the palaeoecological and palaeoenvironmental study of southern Europe during the Early Pleistocene. Thus, research has been focused on Venta Micena 3, which was originally interpreted as a single palaeosurface associated with a marshy context, in which most of the fauna was accumulated by Pachycrocuta brevirostris. Recent excavations have unearthed a new site, Venta Micena 4, located in the same stratigraphic unit (Unit C) and in close proximity to Venta Micena 3. Here we show the first analyses regarding the taphonomic and spatial nature of this new site, defining two stratigraphic boundaries corresponding to two different depositional events. Furthermore, the taphonomic analyses of fossil remains seem to indicate a different accumulative agent than Pachycrocuta, thus adding more complexity to the palaeobiological interpretation of the Venta Micena area. These results contribute to the discussion of traditional interpretations made from Venta Micena 3.Peer reviewe

Robust abandoned object detection integrating wide area visual surveillance and social context

This paper presents a video surveillance framework that robustly and efficiently detects abandoned objects in surveillance scenes. The framework is based on a novel threat assessment algorithm which combines the concept of ownership with automatic understanding of social relations in order to infer abandonment of objects. Implementation is achieved through development of a logic-based inference engine based on Prolog. Threat detection performance is conducted by testing against a range of datasets describing realistic situations and demonstrates a reduction in the number of false alarms generated. The proposed system represents the approach employed in the EU SUBITO project (Surveillance of Unattended Baggage and the Identification and Tracking of the Owner)

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Pliocene to Middle Pleistocene climate history in the Guadix-Baza Basin, and the environmental conditions of early Homo dispersal in Europe

The Guadix-Baza Basin (GBB) in Andalucia, Spain, comprises palaeontological and archaeological sites dating from the Early Pliocene to the Middle Pleistocene, including some of the earliest sites with evidence for the presence of early humans (Homo sp.) in Europe. Thus, the history of climate and environments in this basin contributes significantly to our understanding of the conditions under which early humans spread into Europe during the Early Pleistocene. Here we present estimates of precipitation and primary productivity in the GBB from the Pliocene to the Middle Pleistocene based on dental ecometrics in fossil communities of large herbivorous mammals, and perform an ecometrics-based distribution modelling to analyse the environmental conditions of Early and Middle Pleistocene human sites in Europe. Our results show that Early Pleistocene humans generally occupied on average relatively diverse habitats with ecotones, such as woodlands and savannas, but avoided very open and harsh (cool or dry) environments. During the Middle Pleistocene in Europe, humans occupied a comparatively much broader range of environments than during the Early Pleistocene, but were on average more concentrated in environments where the dental ecometric of mammals indicate wooded palaeoenvironments. In the earliest human occupation sites of the GBB, Barranco Leon and Fuente Nueva 3, the mean annual precipitation and net primary production estimates indicate climatic conditions close to modern Mediterranean sclerophyllous woodland environments, but with slightly higher primary productivity, indicating some similarity with East African woodlands. On the other hand, the environments did not resemble African grassland savannas. The browse-dominated diets of ungulates from Barranco Leon and Fuente Nueva 3 further suggest palaeoenvironments where grasses were a minor component of the vegetation. In the slightly older site of Venta Micena that has no evidence for the presence of hominins, dental ecometric estimates indicate climate and environments similar to Mediterranean "forest steppe" environments existing in the surroundings of Baza today. Grasses were prevalent in the diet of some taxa, especially equids, in Venta Micena, but most of the species show browse-dominated diets even there. (C) 2021 The Authors. Published by Elsevier Ltd.Peer reviewe

Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B

BACKGROUND: The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines METHODS: We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). RESULTS: The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. CONCLUSION: These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied