Predicting responders to prone positioning in mechanically ventilated patients with COVID-19 using machine learning

Background: For mechanically ventilated critically ill COVID-19 patients, prone positioning has quickly become an important treatment strategy, however, prone positioning is labor intensive and comes with potential adverse effects. Therefore, identifying which critically ill intubated COVID-19 patients will benefit may help allocate labor resources. Methods: From the multi-center Dutch Data Warehouse of COVID-19 ICU patients from 25 hospitals, we selected all 3619 episodes of prone positioning in 1142 invasively mechanically ventilated patients. We excluded episodes longer than 24 h. Berlin ARDS criteria were not formally documented. We used supervised machine learning algorithms Logistic Regression, Random Forest, Naive Bayes, K-Nearest Neighbors, Support Vector Machine and Extreme Gradient Boosting on readily available and clinically relevant features to predict success of prone positioning after 4 h (window of 1 to 7 h) based on various possible outcomes. These outcomes were defined as improvements of at least 10% in PaO2/FiO2 ratio, ventilatory ratio, respiratory system compliance, or mechanical power. Separate models were created for each of these outcomes. Re-supination within 4 h after pronation was labeled as failure. We also developed models using a 20 mmHg improvement cut-off for PaO2/FiO2 ratio and using a combined outcome parameter. For all models, we evaluated feature importance expressed as contribution to predictive performance based on their relative ranking. Results: The median duration of prone episodes was 17 h (11-20, median and IQR, N = 2632). Despite extensive modeling using a plethora of machine learning techniques and a large number of potentially clinically relevant features, discrimination between responders and non-responders remained poor with an area under the receiver operator characteristic curve of 0.62 for PaO2/FiO2 ratio using Logistic Regression, Random Forest and XGBoost. Feature importance was inconsistent between models for different outcomes. Notably, not even being a previous responder to prone positioning, or PEEP-levels before prone positioning, provided any meaningful contribution to predicting a successful next proning episode. Conclusions: In mechanically ventilated COVID-19 patients, predicting the success of prone positioning using clinically relevant and readily available parameters from electronic health records is currently not feasible. Given the current evidence base, a liberal approach to proning in all patients with severe COVID-19 ARDS is therefore justified and in particular regardless of previous results of proning. Keywords: Acute respiratory distress syndrome; COVID-19; Mechanical ventilation

Should we teach linear algebra through geometry?

AbstractCan geometry help students learn linear algebra? I study this question and demonstrate that there is no obvious clear answer: geometry can be an obstacle to learning linear algebra; or it can be helpful. Geometry is helpful only under certain conditions and with a specific use of drawings. These special requirements for using geometry are apparently not much recognized in our teaching of linear algebra courses, at least in France, where my educational studies have taken place

PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease

Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters

Comparative interactomics analysis of different ALS-associated proteins identifies converging molecular pathways

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment available. An increasing number of genetic causes of ALS are being identified, but how these genetic defects lead to motor neuron degeneration and to which extent they affect common cellular pathways remains incompletely understood. To address these questions, we performed an interactomic analysis to identify binding partners of wild-type (WT) and ALS-associated mutant versions of ATXN2, C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal cells. This analysis identified several known but also many novel binding partners of these proteins. Interactomes of WT and mutant ALS proteins were very similar except for OPTN and UBQLN2, in which mutations caused loss or gain of protein interactions. Several of the identified interactomes showed a high degree of overlap: shared binding partners of ATXN2, FUS and TDP-43 had roles in RNA metabolism; OPTN- and UBQLN2-interacting proteins were related to protein degradation and protein transport, and C9orf72 interactors function in mitochondria. To conf

Active afforestation of drained peatlands is not a viable option under the EU Nature Restoration Law

The EU Nature Restoration Law (NRL) is critical in restoring degraded ecosystems. However, active afforestation of degraded peatlands has been suggested by some as a restoration measure under the NRL. Here, we discuss the current state of scientific evidence on the climate mitigation effects of peatlands under forestry and its limitations, uncertainties and evidence gaps. Based on this discussion we conclude: Afforestation of drained peatlands, while maintaining their drained state, is not equivalent to ecosystem restoration. This approach will not restore the peatland ecosystem's flora, fauna, and functions. There is insufficient evidence to support the long-term climate change mitigation benefits of active afforestation of drained peatlands. Most studies only focus on the short-term gains in standing biomass and rarely explore the full life cycle emissions associated with afforestation of drained peatlands. Thus, it is unclear whether the CO2 sequestration of a forest on drained peatland can offset the carbon loss from the peat over the long term. In some ecosystems, such as abandoned or certain cutaway peatlands, afforestation may provide short-term benefits for climate change mitigation compared to taking no action. However, this approach violates the concept of sustainability by sacrificing the most space-effective carbon store of the terrestrial biosphere, the long-term peat store, for a shorter-term, less space-effective, and more vulnerable carbon store, namely tree biomass. Consequently, active afforestation of drained peatlands is not a viable option for climate mitigation under the EU Nature Restoration Law and might even impede future rewetting/restoration efforts. To restore degraded peatlands, hydrological conditions must first be improved, primarily through rewetting

Species trait shifts in vegetation and soil seed bank during fen degradation

Fens in Central Europe are characterised by waterlogged organic substrate and low productivity. Human-induced changes due to drainage and mowing lead to changes in plant species composition from natural fen communities to fen meadows and later to over-drained, degraded meadows. Moderate drainage leads to increased vegetation productivity, and severe drainage results in frequent soil disturbances and less plant growth. In the present article, we analyse changes in plant trait combinations in the vegetation and the soil seed bank as well as changes in the seed bank types along gradient of drainage intensity. We hypothesize that an increase in productivity enhances traits related to persistence and that frequent disturbance selects for regeneration traits. We use multivariate statistics to analyse data from three disturbance levels: undisturbed fen, slightly drained fen meadow and severely drained degraded meadow. We found that the abundance of plants regenerating from seeds and accumulating persistent seed banks was increasing with degradation level, while plants reproducing vegetatively were gradually eliminated along the same trajectory. Plants with strong resprouting abilities increased during degradation. We also found that shifts in trait combinations were similar in the aboveground vegetation and in soil seed banks. We found that the density of short-term persistent seeds in the soil is highest in fen meadows and the density of long-term persistent seeds is highest in degraded meadows. The increase in abundance of species with strong regeneration traits at the cost of species with persistence-related traits has negative consequences for the restoration prospects of severely degraded sites

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy