Advection, diffusion and delivery over a network

Many biological, geophysical and technological systems involve the transport of resource over a network. In this paper we present an algorithm for calculating the exact concentration of resource at any point in space or time, given that the resource in the network is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. We consider the implications of advection, diffusion and delivery for simple models of glucose delivery through a vascular network, and conclude that in certain circumstances, increasing the volume of blood and the number of glucose transporters can actually decrease the total rate of glucose delivery. We also consider the case of empirically determined fungal networks, and analyze the distribution of resource that emerges as such networks grow over time. Fungal growth involves the expansion of fluid filled vessels, which necessarily involves the movement of fluid. In three empirically determined fungal networks we found that the minimum currents consistent with the observed growth would effectively transport resource throughout the network over the time-scale of growth. This suggests that in foraging fungi, the active transport mechanisms observed in the growing tips may not be required for long range transport.Comment: 54 pages including appendix, 10 figure

First gene-edited calf with reduced susceptibility to a major viral pathogen

Bovine viral diarrhea virus (BVDV) is one of the most important viruses affecting the health and well-being of bovine species throughout the world. Here, we used CRISPR-mediated homology-directed repair and somatic cell nuclear transfer to produce a live calf with a six amino acid substitution in the BVDV binding domain of bovine CD46. The result was a gene-edited calf with dramatically reduced susceptibility to infection as measured by reduced clinical signs and the lack of viral infection in white blood cells. The edited calf has no off-target edits and appears normal and healthy at 20 months of age without obvious adverse effects from the on-target edit. This precision bred, proof-of-concept animal provides the first evidence that intentional genome alterations in the CD46 gene may reduce the burden of BVDV-associated diseases in cattle and is consistent with our stepwise, in vitro and ex vivo experiments with cell lines and matched fetal clones

Deep-water circulation changes lead North Atlantic climate during deglaciation.

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing

Deep-water circulation changes lead North Atlantic climate during deglaciation

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Biological transport networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system, and we can photograph their growth, digitize the network structure, and measure the movement of radio-tracers. Mycelial networks are more accessible than the transport networks of other multicellular organisms, but there are many open questions concerning the coordination of growth and transport within fungal networks. As osmotically driven water uptake is often distal from the growing margin, and aqueous fluids are effectively incompressible, we propose that growth induces mass flows across the mycelium, towards the growing regions. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and cords that were predicted to carry large currents were significantly more likely to increase in size than cords with small currents. We have also developed an efficient method for calculating the exact quantity of resource in each part of an arbitrary network, where the resource is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. This method enabled us to model the spatial distribution of resource that emerges as a fungal network grows over time, and we found good empirical agreement between our model and experimental data gathered using radio-labelled tracers. Our results suggest that in well insulated fungal networks, growth-induced mass flow is sufficient to account for long distance transport. We conclude that active transport mechanisms may only be required at the very end of the transport pathway, near the growing tips. We also developed a simple model of glucose delivery through vascular networks, which indicates that increasing the number of blood vessels in a region can actually decrease the total rate of glucose delivery

Biological transport networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system, and we can photograph their growth, digitize the network structure, and measure the movement of radio-tracers. Mycelial networks are more accessible than the transport networks of other multicellular organisms, but there are many open questions concerning the coordination of growth and transport within fungal networks. As osmotically driven water uptake is often distal from the growing margin, and aqueous fluids are effectively incompressible, we propose that growth induces mass flows across the mycelium, towards the growing regions. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and cords that were predicted to carry large currents were significantly more likely to increase in size than cords with small currents. We have also developed an efficient method for calculating the exact quantity of resource in each part of an arbitrary network, where the resource is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. This method enabled us to model the spatial distribution of resource that emerges as a fungal network grows over time, and we found good empirical agreement between our model and experimental data gathered using radio-labelled tracers. Our results suggest that in well insulated fungal networks, growth-induced mass flow is sufficient to account for long distance transport. We conclude that active transport mechanisms may only be required at the very end of the transport pathway, near the growing tips. We also developed a simple model of glucose delivery through vascular networks, which indicates that increasing the number of blood vessels in a region can actually decrease the total rate of glucose delivery.</p

Biological transport networks

Cord-forming fungi form extensive networks that continuously adapt to maintain an efficient transport system, and we can photograph their growth, digitize the network structure, and measure the movement of radio-tracers. Mycelial networks are more accessible than the transport networks of other multicellular organisms, but there are many open questions concerning the coordination of growth and transport within fungal networks. As osmotically driven water uptake is often distal from the growing margin, and aqueous fluids are effectively incompressible, we propose that growth induces mass flows across the mycelium, towards the growing regions. We imaged the temporal evolution of networks formed by Phanerochaete velutina, and at each stage calculated the unique set of currents that account for the observed changes in cord volume, while minimizing the work required to overcome viscous drag. Predicted speeds were in reasonable agreement with experimental data, and cords that were predicted to carry large currents were significantly more likely to increase in size than cords with small currents. We have also developed an efficient method for calculating the exact quantity of resource in each part of an arbitrary network, where the resource is lost or delivered out of the network at a given rate, while being subject to advection and diffusion. This method enabled us to model the spatial distribution of resource that emerges as a fungal network grows over time, and we found good empirical agreement between our model and experimental data gathered using radio-labelled tracers. Our results suggest that in well insulated fungal networks, growth-induced mass flow is sufficient to account for long distance transport. We conclude that active transport mechanisms may only be required at the very end of the transport pathway, near the growing tips. We also developed a simple model of glucose delivery through vascular networks, which indicates that increasing the number of blood vessels in a region can actually decrease the total rate of glucose delivery.</p

Deep-water circulation changes lead North Atlantic climate during deglaciation.

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing