Embedding of biological regulatory networks and property preservation

Abstract. In the course of understanding biological regulatory networks (BRN), scientists usually start by studying small BRNs that they believe to be of particular importance to represent a biological function, and then, embed them in a larger network. Such a reduction can lead to neglect relevant regulations and to study a network whose properties can be very different from the properties of this network viewed as a part of the whole. In this paper we study, from a logical point of view, on which conditions concerning both networks, properties can be inherited by BRNs from sub-BRNs. We give some conditions on the nature of the network embeddings ensuring that dynamic properties on the embedded sub-BRNs are preserved at the level of the whole BRN

Comparison of two paradigms based on stimulation with images in a spelling brain-computer interface.

A BCI Speller is a typical Brain-Computer Interface (BCI) system for communication purposes. This technology can provide users with severe motor disability with an assistive device controlled by brain activity. The present preliminary study, with only four subjects, is focused on the control of a 5x5 P300-based speller matrix for communication purposes. In this work, we study the effect of flashing stimuli used to highlight the letters in two conditions: pictures and red famous faces (that is, famous faces coloured in red). These preliminary results, based on performance and the Information Transfer Rate (ITR), showed that both conditions are similar, obtaining very good performance compared to conventional P300-speller. In this sense, the use of pictures does not make the performance worse, allowing to develop more attractive and usable interfaces. More tests would confirm if there is a difference in performance between the two conditions proposed.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

De 20 000 à 18 000 BP en Quercy : apports de la séquence du Cuzoul de Vers à la compréhension de l'évolution des comportements socio-économiques entre Solutréen récent et Badegoulien

Essai de synthèse des travaux menés autour du gisement du Cuzoul de Vers (Lot)

Recent Laborian of the Peyrazet cave-rock shelter (Creysse, Lot, France). New data for the end of Lateglacial in Quercy

Découverte en 1990, la grotte-abri de Peyrazet (Creysse, Lot, France) se situe dans le Haut-Quercy en bordure du causse de Martel, à quelques centaines de mètres du cours actuel de la Dordogne. Les fouilles menées depuis 2008 livrent une archéoséquence du Tardiglaciaire qui permet de combler certaines lacunes documentaires régionales et plus largement du Sud-Ouest de la France. Au Magdalénien supérieur succède un niveau ayant donné des indices d’un Azilien sensu lato stratigraphiquement séparé du Laborien, ensemble supérieur qui fait l’objet de cet article. Jusqu’alors ce technocomplexe de la fin du Pléistocène et des débuts de l’Holocène demeurait mal connu dans la région. En effet, seuls des travaux anciens menés dans deux gisements permettaient de noter sa présence en Quercy. La découverte d’un ensemble laborien récent (ou Épilaborien) à Peyrazet est l’occasion de conduire une étude collective des divers vestiges dans un cadre archéostratigraphique mieux maîtrisé. L’analyse géoarchéologique met en évidence l’action conjointe du ruissellement et de l’éboulisation comme principaux responsables de la mise en place des dépôts. Dans la partie S-O du site, un lithofaciès de remaniement indique une bioturbation importante en lien avec le creusement de terriers. Bien que leur origine ne soit pas liée aux activités humaines, les rongeurs, les oiseaux, les poissons et les mésomammifères (excepté le lièvre) apportent des données concernant l’environnement des chasseurs-cueilleurs. La grande faune est dominée par le cerf dont les carcasses pourraient avoir été introduites incomplètes sur le site puis traitées pour en extraire la viande et la moelle. Nous avons bénéficié d’une analyse fonctionnelle croisée à l’étude typo-technologique des vestiges lithiques composés pour l’essentiel de silex locaux et régionaux. Ce double regard a permis de mettre en évidence une diversité d’activités mise en œuvre dans la cavité. Une pièce d’ocre rouge, quelques vestiges d’industrie osseuse et des éléments de parure participent également à la description d’une large gamme de tâches effectuées lors d’un séjour prolongé ou de plusieurs occupations successives. La comparaison des pointes de chasse microlithiques avec d’autres gisements sur une vaste échelle géographique conduit à discuter l’attribution de cet ensemble supérieur à différentes phases du Laborien. L’hypothèse d’un Laborien récent (ou Épilaborien) conduit à réfléchir à une perduration de morphotypes ancestraux parallèlement à de nouveaux types d’armatures, observation déjà réalisée notamment à La Borie del Rey dans le Haut-Agenais mais qui demande encore des précisions et de nouvelles découvertes.Discovered in 1990, Peyrazet cave-rock shelter (Creysse, Lot) lies in the Haut-Quercy region at the limits of the Martel limestone plateau, several hundred meters from the current Dordogne River valley. Excavations begun in 2008 produced a Late Glacial archaeo-sequence that sheds new light on several still poorly understood aspects of the archeological record in both the Haut-Quercy region and southwestern France in general. The level overlying the Late Magdalenian occupation produced limited evidence for the Azilian and is stratigraphically separated from the Laborian. This latter techno-complex, dated to the end of the Pleistocene and early Holocene, remains poorly documented in the region, having only been previously identified from two sites in the Quercy. The discovery of a recent Laborian (Epilaborian) occupation at Peyrazet presented the ideal occasion for a collaborative study of the diverse archaeological material recovered from this well-understood archaeo-stratigraphic context. A geoarchaeological analysis produced evidence for both surface runoff and the accumulation of coarse deposits (éboulis) as the principal site formation processes. In the southwest area of the site, a reworked lithofacies demonstrates substantial bioturbation in connection with animal burrowing. Although the presence of rodent, bird, fish, and medium-sized mammals (except hare) cannot be definitively connected to human activity, they nevertheless provide important information concerning the environments exploited by hunter-gatherer groups. Larger species are dominated by red deer whose carcasses were partially processed before being introduced to the site, where meat was subsequently removed and marrow consumed. A functional analysis combined with a typo-technological study of the primarily locally- and regionally-procured lithic material revealed evidence for diverse activities having taken place on-site. An ochre fragment, several bone tools and ornaments equally indicate a large variety of tasks to have been carried out during a single, long occupation or several successive visits. A typo-technological comparison of hunting weaponry (microliths) from sites across a substantial area suggests the assemblage to represent either a Laborian/Epilaborian mix or a unique Epilaborian occupation. This latter case would indicate the persistence of older morphotypes alongside the development of new tools forms, a situation already identified at Borie del Rey in the Haut-Agenais but which requires more detailed study supported by new discoveries

Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery

ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030