Feed-Forward Optimization With Delayed Feedback for Neural Networks

Backpropagation has long been criticized for being biologically implausible, relying on concepts that are not viable in natural learning processes. This paper proposes an alternative approach to solve two core issues, i.e., weight transport and update locking, for biological plausibility and computational efficiency. We introduce Feed-Forward with delayed Feedback (F$^3$), which improves upon prior work by utilizing delayed error information as a sample-wise scaling factor to approximate gradients more accurately. We find that F$^3$ reduces the gap in predictive performance between biologically plausible training algorithms and backpropagation by up to 96%. This demonstrates the applicability of biologically plausible training and opens up promising new avenues for low-energy training and parallelization

Internal diameter coating by warm spraying of fine WC-12Co powders (− 10 + 2 µm) with very short spray distances up to 10 mm

The internal diameter (ID) coating by means of thermal spraying is currently experiencing growing interest in science and industry. In contrast to the well-established plasma- and arc-based spray techniques, there is a lack of knowledge concerning kinetic processes such as HVOF, HVAF and warm spray (WS). A major challenge represents the necessity of short spray distances and the compact design of novel ID spray guns with reduced combustion power. Conventional WC-Co powders (− 45 + 15 µm) are not able to achieve a sufficient heat and momentum transfer. The use of fine powders < 15 µm offers an approach to overcome this drawback as they feature a larger surface-to-volume ratio and a lower mass. However, the processing of fine powders requires suitable spray equipment and a sensitive parameter adjustment. In this study, warm spraying of fine WC-12Co powders (− 10 + 2 µm) with a novel ID spray gun (HVOF + N2) “ID RED” (Thermico Engineering GmbH, Germany) was investigated. First, the flame profile as well as the in-flight behavior of the particles along the spray jet (spray distances SD = 10-80 mm) was analyzed at different nitrogen flows NF = 15-115 L/min to find suitable spray parameter intervals. Subsequently, planar steel samples were coated with SD = 10-50 mm and constant NF = 90 L/min. Analyses regarding the microstructure, the mechanical properties and the phase evolution of the coatings were performed. The aim was to study spraying with the novel ID gun and to scrutinize shortest feasible spray distances. Finally, steel tubes (internal diameter of 81.6 mm and a wall thickness of 10.0 mm) were coated with SD = 20 mm and NF = 90 L/min to investigate in how far the results can be transferred to ID parts. Correlations between the particle behavior, the microstructure and the coating properties were made

Model-Based Analysis of SARS-CoV-2 Infections, Hospitalization and Outcome in Germany, the Federal States and Districts

The coronavirus disease 2019 (COVID-19) pandemic challenged many national health care systems, with hospitals reaching capacity limits of intensive care units (ICU). Thus, the estimation of acute local burden of ICUs is critical for appropriate management of health care resources. In this work, we applied non-linear mixed effects modeling to develop an epidemiological SARS-CoV-2 infection model for Germany, with its 16 federal states and 400 districts, that describes infections as well as COVID-19 inpatients, ICU patients with and without mechanical ventilation, recoveries, and fatalities during the first two waves of the pandemic until April 2021. Based on model analyses, covariates influencing the relation between infections and outcomes were explored. Non-pharmaceutical interventions imposed by governments were found to have a major impact on the spreading of SARS-CoV-2. Patient age and sex, the spread of variant B.1.1.7, and the testing strategy (number of tests performed weekly, rate of positive tests) affected the severity and outcome of recorded cases and could reduce the observed unexplained variability between the states. Modeling could reasonably link the discrepancies between fine-grained model simulations of the 400 German districts and the reported number of available ICU beds to coarse-grained COVID-19 patient distribution patterns within German regions

Influence of wind speed and wind direction above the sea surface on the diffusive methane flux and the atmospheric methane concentration at the North Sea

The estimations of the diffusive methane flux from the water phase into the atmosphere in coastal waters is relevant for a better estimate of the atmospheric greenhouse-gas budget. Unfortunately, so far, the numerical determination of the fluxes has a high level of uncertainty in coastal waters. To improve the estimation of coastal methane fluxes, not only a high temporal and spatial sampling resolution of the dissolved methane in the water are required. Besides, also the atmospheric methane concentration and the wind speed and wind direction above the surface is important. In most cases, these atmospheric data are obtained from near-by atmospheric and meteorologic monitoring stations. In this study, we measured wind speed, direction and atmospheric methane local directly on board of three research vessel cruising in the southern North Sea within the MOSES project and compared the effects of local versus remote measurements of these data on the flux data. In addition, using the wind direction and speed, we try to assess the origin of the atmospheric methane measured in the study area. Using these “improved” data sets, we discuss if local measurements of auxiliary data provide better insights in the determining factors of the methane flux, and thus also improve the regional aquatic methane budget

Population pharmacokinetic modeling of multiple-dose intravenous fosfomycin in critically ill patients during continuous venovenous hemodialysis

The aim of this study was to investigate the pharmacokinetics of multiple-dose intravenous (i.v.) fosfomycin in critically ill patients during continuous venovenous hemodialysis (CVVHD). Noncompartmental analysis and population pharmacokinetic modeling were used to simulate diferent dosing regimens. We evaluated 15 critically ill patients with renal insufciency and CVVHD undergoing anti-infective treatment with fosfomycin in our ICU. Five grams of fosfomycin were administered for 120 min every 6 h. Plasma concentrations were determined with and without CVVHD. Pharmacokinetic analysis and simulations were performed using non-linear mixed efects modelling (NONMEM). A two-compartment model with renal and dialysis clearance was most accurate in describing the pharmacokinetics of i.v. fosfomycin during CVVHD. Population parameter estimates were 18.20 L and 20.80 L for the central and peripheral compartment volumes, and 0.26 L/h and 5.08 L/h for renal and intercompartmental clearance, respectively. Urinary creatinine clearance (CLCR) represented a considerable component of renal clearance. Central compartment volume increased over time after the frst dose. For patients with CLCR > 50 (90) mL/min and CVVHD, dosage should be increased to≥ 15 (16) grams of i.v. fosfomycin across three (four) daily doses. Individual CLCR must be considered when dosing i.v. fosfomycin in critically ill patients during CVVHD

Report and preliminary results of R/V POSEIDON cruise POS539, Varna (Bulgaria) - Varna (Bulgaria) November 6 - November 21, 2019

The R/V POSEIDON cruise POS539 took place in the northwestern basin of the Black Sea (42°30’N to 44°N and 29°E to 31°E). The overarching aim of the campaign was to obtain sediment and water samples, including suspended particle material, from the various redox zones of the Black Sea. The campaign lasted between November 6th and November 21st 2019 and the collected samples were taken in order to investigate the activity and physiology of microorganisms involved in the conversion of nitrogen compounds and degradation of organic carbon under various oxygen conditions. The main topics of the cruise were: (a) to quantify the contribution of archaeal nitrifiers to the nitrogen and carbon cycles, b) to measure the production and consumption of the powerful greenhouse gases CH4 and N2O, c) to record palaeoenvironmental changes in high resolution, and d) to describe the complexity and identity of biopolymers. For this, water and sediment samples were retrieved from 10 discrete shelf and slope stations. First, ‘deep water’ transect was conducted, which included three stations with water depths over 2000 m. The second perpendicular transect encompassed stations that gradually transitioned from the deep parts of the slope towards the shelf (ca. 80 m depth). Additionally, two stations were setup north and south of the shelf transect, respectively, for paleoceanographic studies. Throughout the cruise the weather conditions were overwhelmingly good, only towards the end of the campaign gusty winds of 7 Bft were recorded. The recorded oceanographic conditions were in agreement with the expected water properties at all stations. Station activities were completed on November 20th at 14:00 local board time. On November 21st at 10:30 local time, R/V POSEIDON reached the port of Varna, Bulgaria, thus concluding the POS539 expedition. Analyses and results from the samples and experiments will provide a basis for our understanding of the microbial control on the carbon and nitrogen cycle of the Black Sea.13032

Nutrient and carbon dynamics along the river-estuary-ocean continuum on Central European scale

Nutrient and carbon dynamics within the river-estuary-coastal water systems are key processes to understand the matter fluxes from the terrestrial environment to the ocean. In a large-scale study we analysed those dynamics with the focus of the prevailing low water conditions by following a sampling approach based on the travel time of water. We started with a nearly Lagrangian sampling along the River Elbe (German part; 580 km within 8 days travel time). After a subsequent investigation of the estuary, the plume of the river was followed by raster sampling the German Bight (North Sea) using three ships simultaneously. In the river, intensive growth of phytoplankton was determined connected with high oxygen saturation and pH values as well as under-saturation of CO2, whereas concentrations of dissolved nutrients declined. In the estuary, the Elbe shifted from an autotrophic to a heterotrophic system: Phytoplankton died off upstream of the salinity gradient causing minima in oxygen saturation and pH, supersaturation of CO2, and a release of nutrients. In the coastal region, phytoplankton and nutrient concentrations were low, oxygen close to saturation, and pH in a typical marine range. We detected a positive relationship between pH values and oxygen saturation and a negative one between pCO2 and oxygen saturation. Corresponding to the significant particulate nutrient flux via phytoplankton, flux rates of dissolved nutrients from the river into the estuary were low and determined by depleted concentrations. In contrast, fluxes from the estuary to the coastal waters were higher and the pattern was determined by tidal currents. Overall, the presented observation approach is appropriate to better understand land-ocean fluxes, particularly if it is performed under different hydrological conditions including extremes and seems to be suitable to investigate the impact of such events in freshwater on coastal systems in future. The study was conducted within the frame of the Helmholtz MOSES initiative (Modular Observation Solutions for Earth Systems) targeting processes and impacts of hydrological extremes

Editorial: Achieving nutrition security in Tanzania by improving production, education and economics: Methods, tools and applications

Peer Reviewe

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism - the Find-AF 2 study - rationale and design

Background Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, i.e. ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Methods Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. Conclusions The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a significant effect on stromal cells, mediated through a druggable MIF-CD74 axis. These data highlight the complex interplay between alterations in the MPN clone and activation of stromal cells and indicate that Gli1 represents a promising therapeutic target in MPNs, particularly that Hh signaling is dispensable for normal hematopoiesis.</p