Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

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

Seismic-induced slump in Early Pleistocene deltaic deposits of the Baza Basin (SE Spain).

13 figures.Early Pleistocene lacustrine deposits of the Baza Basin in SE Spain show a 2 m thick sheet with deformation structures intercalated within horizontal strata. Along a 180 m exposure we recognise an alternation of compressional (thrusts) and extensional (normal faults and tensional joints) structures. These structures are interpreted as a planar slump. Analysis of the different structures together with the sedimentary facies indicates that this slump moved towards the north in a subaqueous deltaic environment 2.5 m deep with a paleoslope of < 1°. An earthquake is presumed to have triggered the mass movement and was followed by other shaking of lesser intensity. These events occurred in rapid succession, during the active deposition of a single delta lobe, which then covered and preserved the structures. The general stratigraphic position of this subaqueous slump matches other nearby liquefaction structures (seismites), indicating a period of active paleoseismicity. This appears to coincide with renewal of tectonic activity in the adjacent Betic Cordillera, which changed the source area of detrital deposits, infilled the NE margin of the Basin, and modified the morphology of the paleo-Lake Baza. Paleomagnetic and biostratigraphic data constrain the age of the structures to the Early Pleistocene, between 1.2 and 1.1 Mya.We thank Ayuntamiento de Orce for a grant to L. G. This research is supported by the research group n°217 from the Junta de Andalucía, the Acc. Esp. BTE2001-5230-E and the Earthwatch Institute. We thank J. Menzies and M. Moretti for review and useful comments on this manuscript.Peer reviewe

Deslizamientos de bajo ángulo en la Cuenca de Baza (Cordillera Bética)

3 páginas.-- Trabajo presentado en el V Congreso del Grupo Español del Terciario Granada, 23-25 de septiembre, 2003.Peer reviewe

Palaeoenvironmental evolution of the Barbate–Trafalgar coast (Cadiz) during the last ~ 140 ka: Climate, sea-level interactions and tectonics

Coastal response to tectonic activity and eustatic-climate interactions during the Late Pleistocene and Holocene has been analyzed along the Barbate–Trafalgar shoreline. The study area consists of an uplifted platform (La Breña, ~140 m) bounded by two major NW–SE faults that have created two subsiding areas: Meca in the west and Barbate in the east. The areas of subsidence have favoured the accumulation of a thick morphosedimentary sequence consisting of (in ascending stratigraphic order) beach, alluvial, and aeolian deposits, which repeatedly underwent soil-forming processes. This study outlines the palaeogeographical evolution of the area over the last ~140 ka, as deduced from geomorphological mapping associated with a range of laboratory analyses (mineralogical, geochemical, magnetic susceptibility, and soil micromorphology analyses), optically stimulated luminescence (OSL dating), and existing U–Th dating. Special attention has been paid to the alluvial unit, made up of vertically stacked sandy sheet-flood deposits with interbedded red paleosols. OSL ages suggest that sediment supply to the alluvial/coastal environments took place mainly at the end of the two most recent glacial periods (Oxygen Isotopic Stage [OIS] 6 and OIS 3/OIS 2) and during the last interglacial period (end of OIS 5). This means that although alluvial sedimentation took place at times of relatively high sea level, these were not times of highstand because very high sea levels (like the present) allow marine erosion of the distal part of the fans (fan toes), cutting cliffed coasts. The repeated occurrence of paleosols in the alluvial sequence seems to indicate a recurrence of environmental changes that modified the feedback relationships between the catchment and the coastal areas. These changes are recorded in repeated oscillations of soil parameters, and are revealed from the results of geochemical and environmental magnetism analyses. We associate repeated pedogenesis and alluvial sedimentation with the glacial/interglacial global climatic changes due to an oscillating humidity/ aridity ratio rather than with cyclicity in thermal regime

Compilación de Proyectos de Investigacion de 1984-2002

Instituto Politecnico Nacional. UPIICS