The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A family of process-based models to simulate landscape use by multiple taxa

Context: Land-use change is a key driver of biodiversity loss. Models that accurately predict how biodiversity might be affected by land-use changes are urgently needed, to help avoid further negative impacts and inform landscape-scale restoration projects. To be effective, such models must balance model realism with computational tractability and must represent the different habitat and connectivity requirements of multiple species. Objectives: We explored the extent to which process-based modelling might fulfil this role, examining feasibility for different taxa and potential for informing real-world decision-making. Methods: We developed a family of process-based models (*4pop) that simulate landscape use by birds, bats, reptiles and amphibians, derived from the well-established poll4pop model (designed to simulate bee populations). Given landcover data, the models predict spatially-explicit relative abundance by simulating optimal home-range foraging, reproduction, dispersal of offspring and mortality. The models were co-developed by researchers, conservation NGOs and volunteer surveyors, parameterised using literature data and expert opinion, and validated against observational datasets collected across Great Britain. Results: The models were able to simulate habitat specialists, generalists, and species requiring access to multiple habitats for different types of resources (e.g. breeding vs foraging). We identified model refinements required for some taxa and considerations for modelling further species/groups. Conclusions: We suggest process-based models that integrate multiple forms of knowledge can assist biodiversity-inclusive decision-making by predicting habitat use throughout the year, expanding the range of species that can be modelled, and enabling decision-makers to better account for landscape context and habitat configuration effects on population persistence

A family of process-based models to simulate landscape use by multiple taxa

Acknowledgements: We would like to thank all the volunteer surveyors who contributed data to the BTO/RSPB/JNCC Breeding Bird Survey and those who contributed data to the Field Survey within the BCT’s National Bat Monitoring Programme, without whom validation of the bird and bat models would not have been possible. We would also like to thank all the volunteer surveyors of Surrey Amphibian and Reptile Group, who kindly contributed their common lizard sightings and enabled validation of the reptile model. Finally, we would like to thank the regional ARGs and all the Toad Patrol volunteers, supported by Froglife, who took the time to fill in the toad habitat use questionnaire, so enabling validation of the amphibian model. EG acknowledges funding from a Research Programme Fellowship provided by the Natural Environment Research Council through UK Research and Innovation’s Landscape Decisions Programme (NE/V007831/1).Context: Land-use change is a key driver of biodiversity loss. Models that accurately predict how biodiversity might be affected by land-use changes are urgently needed, to help avoid further negative impacts and inform landscape-scale restoration projects. To be effective, such models must balance model realism with computational tractability and must represent the different habitat and connectivity requirements of multiple species. Objectives: We explored the extent to which process-based modelling might fulfil this role, examining feasibility for different taxa and potential for informing real-world decision-making. Methods: We developed a family of process-based models (*4pop) that simulate landscape use by birds, bats, reptiles and amphibians, derived from the well-established poll4pop model (designed to simulate bee populations). Given landcover data, the models predict spatially-explicit relative abundance by simulating optimal home-range foraging, reproduction, dispersal of offspring and mortality. The models were co-developed by researchers, conservation NGOs and volunteer surveyors, parameterised using literature data and expert opinion, and validated against observational datasets collected across Great Britain. Results: The models were able to simulate habitat specialists, generalists, and species requiring access to multiple habitats for different types of resources (e.g. breeding vs foraging). We identified model refinements required for some taxa and considerations for modelling further species/groups. Conclusions: We suggest process-based models that integrate multiple forms of knowledge can assist biodiversity-inclusive decision-making by predicting habitat use throughout the year, expanding the range of species that can be modelled, and enabling decision-makers to better account for landscape context and habitat configuration effects on population persistence

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

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

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

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

International audienceIn 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