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Building resilience into today’s complex infrastructures is critical to the daily functioning of society and its ability to withstand and recover from natural disasters, epidemics and cyber-threats. This study proposes quantitative measures that capture and implement the definition of engineering resilience advanced by the National Academy of Sciences. The approach is applicable across physical, information and social domains. It evaluates the critical functionality, defined as a performance function of time set by the stakeholders. Critical functionality is a source of valuable information, such as the integrated system resilience over a time interval and its robustness. The paper demonstrates the formulation on two classes of models: 1) multi-level directed acyclic graphs and 2) interdependent coupled networks. For both models synthetic case studies are used to explore trends. For the first class, the approach is also applied to the Linux operating system. Results indicate that desired resilience and robustness levels are achievable by trading off different design parameters, such as redundancy, node recovery time and backup supply available. The nonlinear relationship between network parameters and resilience levels confirms the utility of the proposed approach, which is of benefit to analysts and designers of complex systems and networks.

Building resilience into today's complex infrastructures is critical to the daily functioning of society and its ability to withstand and recover from natural disasters, epidemics, and cyber-threats. This study proposes quantitative measures that implement the definition of engineering resilience advanced by the National Academy of Sciences. The approach is applicable across physical, information, and social domains. It evaluates the critical functionality, defined as a performance function of time set by the stakeholders. Critical functionality is a source of valuable information, such as the integrated system resilience over a time interval, and its robustness. The paper demonstrates the formulation on two classes of models: 1) multi-level directed acyclic graphs, and 2) interdependent coupled networks. For both models synthetic case studies are used to explore trends. For the first class, the approach is also applied to the Linux operating system. Results indicate that desired resilience and robustness levels are achievable by trading off different design parameters, such as redundancy, node recovery time, and backup supply available. The nonlinear relationship between network parameters and resilience levels confirms the utility of the proposed approach, which is of benefit to analysts and designers of complex systems and networks.

Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. Here we present two crystal structures of FP and two structures of convertase bound FP. A structural core formed by three thrombospondin repeats (TSRs) and a TB domain harbors the convertase binding site in FP that mainly interacts with C3b. Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. Intermolecular contacts between FP and the convertase subunits suggested by the structure were confirmed by binding experiments. FP is shown to inhibit C3b degradation by FI due to a direct competition for a common binding site on C3b. FP oligomers are held together by two sets of intermolecular contacts, where the first is formed by the TB domain from one FP molecule and TSR4 from another. The second and largest interface is formed by TSR1 and TSR6 from the same two FP molecules. Flexibility at four hinges between thrombospondin repeats is suggested to enable the oligomeric, polydisperse, and extended architecture of FP. Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition.

Patients admitted to the Intensive Care Unit (ICU) can experience significant fluctuations in blood glucose levels, even if they do not have a history of diabetes. Such variations may arise from multiple causes and are part of the adaptative stress-response to critical illness. To support their nutritional needs, these patients might also need parenteral feeding. Glucose and metabolic fluctuations can lead to serious consequences, including increased infection rates, loss in protein and muscle mass and increased morbi-mortality. This justifies precise and constant monitoring. The management of insulin therapy and nutritional therapy strongly impacts the outcomes of critically ill patients. Glucosafe 2 (GS2) is an innovative medical device designed to address these needs. It offers real-time recommendations to healthcare professionals regarding blood glucose control and nutritional inputs among ICU patients. The goal is to ensure that blood glucose levels remain within the desired range of targeted values, and consequently to minimize the risk of both hypo- and hyperglycemia. This study is an unblinded randomized controlled study with: (1) the intervention group, which uses the GS2 device for nutritional therapy and blood glucose advice until discharge from the ICU or up until 15 days after study enrolment; (2) the control group, which uses standard care according to local ICU protocols. We also collected data of a third historical control group using retrospective data from a sample of ICU patients exposed to the standard of care 2 years before the start of the prospective trial; it aims first to validate the predictive accuracy of the GS2 model before the start of the prospective parts and to interpret the existence of possible bias by assessing the potential cross-contamination effects between intervention and control group, due to the fact that caregivers can take more care of patients in the control group, which will dilute the effect of GS2. We planned to enrol 71 patients per group (total =  213 patients). The primary objective is to compare the time spent within a predetermined range of glycemia (5.0 - 8.5 mmol/l) between the intervention group (GS2) and the control group (standard local ICU protocols). This study aims to evaluate the performance and safety of the GS2 medical device software to monitor and guide blood glucose management and nutritional therapy in critically ill patients in comparison to current standard of care. If proven successful, GS2 could be used to optimize nutritional and blood glucose management. The clinical data gathered from this study will also contribute to the Clinical Evaluation Report (CER), a regulatory document that provides an assessment of the clinical safety and performance of a medical device throughout its intended lifecycle. GS2 has the potential to optimize the quality of nutritional and blood glucose management and improve compliance with international guidelines. ClinicalTrials.gov, NCT03890432, Registered on 26 March 2019.

We present the AIMe registry, a community-driven reporting platform for AI in biomedicine. It aims to enhance the accessibility, reproducibility and usability of biomedical AI models, and allows future revisions by the community.

The Southern Ocean is a major sink of anthropogenic CO2 and an important foraging area for top trophic level consumers. However, iron limitation sets an upper limit to primary productivity. Here we report on a considerably dense late summer phytoplankton bloom spanning 9000 km2 in the open ocean of the eastern Weddell Gyre. Over its 2.5 months duration, the bloom accumulated up to 20 g C m−2 of organic matter, which is unusually high for Southern Ocean open waters. We show that, over 1997–2019, this open ocean bloom was likely driven by anomalies in easterly winds that push sea ice southwards and favor the upwelling of Warm Deep Water enriched in hydrothermal iron and, possibly, other iron sources. This recurring open ocean bloom likely facilitates enhanced carbon export and sustains high standing stocks of Antarctic krill, supporting feeding hot spots for marine birds and baleen whales.

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.

Autonomic nerves control organ function through the sympathetic and parasympathetic branches, which have opposite effects. In the bone marrow, sympathetic (adrenergic) nerves promote hematopoiesis; however, how parasympathetic (cholinergic) signals modulate hematopoiesis is unclear. Here, we show that B lymphocytes are an important source of acetylcholine, a neurotransmitter of the parasympathetic nervous system, which reduced hematopoiesis. Single-cell RNA sequencing identified nine clusters of cells that expressed the cholinergic α7 nicotinic receptor (Chrna7) in the bone marrow stem cell niche, including endothelial and mesenchymal stromal cells (MSCs). Deletion of B cell-derived acetylcholine resulted in the differential expression of various genes, including Cxcl12 in leptin receptor+ (LepR+) stromal cells. Pharmacologic inhibition of acetylcholine esterase decreased the systemic supply of inflammatory myeloid cells in mice and humans with cardiovascular disease.Nahrendorf and colleagues show that B cells in the bone marrow are an important source of the neurotransmitter acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche during steady-state and emergency hematopoiesis.

Organic and low-input systems are proposed as ways to reduce the environmental impacts of agriculture. Previous studies have shown that yields of organic systems can be ∼19 to 25% lower than conventional systems. An intermediary, low-input system could be less damaging for the environment than conventional systems, while reducing yield losses in comparison with organic systems. In this study, we performed a meta-analysis to compare low-input systems to conventional and organic systems. Our analysis is based on data of cropping system experiments conducted in Europe and North America, and focuses on two important crops, maize (Zea mays L.) and soft winter wheat (Triticum aestivum L.). Pesticide use was greatly reduced for low-input systems as compared with conventional for the two crops (50% for maize, 70% for wheat on average). Mean mineral N use was also reduced by 36% for maize and 28% for wheat in low-input relative to conventional. Maize yields in low-input systems were not different from those in conventional systems, and were higher than yields in organic systems (yield ratio of low-input vs. organic = 1.24). Wheat yields in low-input systems were lower than yields in conventional systems (yield ratio of low-input vs. conventional = 0.88), but were substantially higher than yields in organic systems (yield ratio of low input vs. organic = 1.43). This is one of the first meta-analyses to assess performance in terms of pesticide use intensity, and yields, with clear evidence emerging that low-input systems can markedly reduce pesticide application, without strongly reducing crop yields, relative to conventional systems.

The Southern Ocean is a major sink of anthropogenic CO2 and an important foraging area for top trophic level consumers. However, iron limitation sets an upper limit to primary productivity. Here we report on a considerably dense late summer phytoplankton bloom spanning 9000 km2 in the open ocean of the eastern Weddell Gyre. Over its 2.5 months duration, the bloom accumulated up to 20 g C m−2 of organic matter, which is unusually high for Southern Ocean open waters. We show that, over 1997–2019, this open ocean bloom was likely driven by anomalies in easterly winds that push sea ice southwards and favor the upwelling of Warm Deep Water enriched in hydrothermal iron and, possibly, other iron sources. This recurring open ocean bloom likely facilitates enhanced carbon export and sustains high standing stocks of Antarctic krill, supporting feeding hot spots for marine birds and baleen whales.