Traveling-wave deceleration of SrF molecules

We report on the production, deceleration and detection of a SrF molecular beam. The molecules are captured from a supersonic expansion and are decelerated in the X$^2\Sigma^+ (v=0, N=1)$ state. We demonstrate the removal of up to 40% of the kinetic energy with a 2 meter long modular traveling-wave decelerator. Our results demonstrate a crucial step towards the preparation of ultracold gases of heavy diatomic molecules for precision spectroscopy

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles

The effect of age on ventilation management and clinical outcomes in critically ill COVID–19 patients—insights from the PRoVENT–COVID study

Introduction: We analyzed the association of age with ventilation practice and outcomes in critically ill COVID–19 patients requiring invasive ventilation. Methods: Posthoc analysis of the PRoVENT–COVID study, an observational study performed in 22 ICUs in the first 3 months of the national outbreak in the Netherlands. The coprimary endpoint was a set of ventilator parameters, including tidal volume normalized for predicted bodyweight, positive end–expiratory pressure, driving pressure, and respiratory system compliance in the first 4 days of invasive ventilation. Secondary endpoints were other ventilation parameters, the use of rescue therapies, pulmonary and extrapulmonary complications in the first 28 days in the ICU, hospital– and ICU stay, and mortality. Results: 1122 patients were divided into four groups based on age quartiles. No meaningful differences were found in ventilation parameters and in the use of rescue therapies for refractory hypoxemia in the first 4 days of invasive ventilation. Older patients received more often a tracheostomy, developed more frequently acute kidney injury and myocardial infarction, stayed longer in hospital and ICU, and had a higher mortality. Conclusions: In this cohort of invasively ventilated critically ill COVID–19 patients, age had no effect on ventilator management. Higher age was associated with more complications, longer length of stay in ICU and hospital and a higher mortality.</p

Development of a Soil Organic Carbon Baseline for Otjozondjupa, Namibia

Land Degradation Neutrality (LDN) has been piloted in 14 countries and will be scaled up to over 120 countries. As a LDN pilot country, Namibia developed sub-national LDN baselines in Otjozondjupa Region. In addition to the three LDN indicators (soil organic carbon, land productivity and land cover change), Namibia also regards bush encroachment as an important form of land degradation. We collected 219 soil profiles and used Random Forest modelling to develop the soil organic carbon stock baseline. Values range between 0.53 and 4.27 kg/m2 in the sandy Otjozondjupa soils. LDN baselines were integrated into other national planning processes to add value to LDN products. Analyses of the relationship between soil carbon and land cover change, especially from grassland to bushland, increased the usefulness of soil carbon maps for the Integrated Regional Land Use Planning process. Local ownership of LDN baseline development, from data collection to digital soil mapping, was crucial for local stakeholders

Traveling-wave deceleration of SrF molecules

We report on the production, deceleration and detection of a SrF molecular beam. The molecules are captured from a supersonic expansion and are decelerated in the

TGF-β activation and function in immunity.

The cytokine TGF-β plays an integral role in regulating immune responses. TGF-β has pleiotropic effects on adaptive immunity, especially in the regulation of effector and regulatory CD4(+) T cell responses. Many immune and nonimmune cells can produce TGF-β, but it is always produced as an inactive complex that must be activated to exert functional effects. Thus, activation of latent TGF-β provides a crucial layer of regulation that controls TGF-β function. In this review, we highlight some of the important functional roles for TGF-β in immunity, focusing on its context-specific roles in either dampening or promoting T cell responses. We also describe how activation of TGF-β controls its function in the immune system, with a focus on the key roles for members of the integrin family in this process

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications–posthoc analysis of two randomised clinical trials in open abdominal surgery

Background: While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods: Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011–2013 and 2014–2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end–expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time–weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings: In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time–weighted average driving pressure and mechanical power were 14·0 [11·0–17·0] cmH2O, and 7·6 [5·1–10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88–1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05–1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation: In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding: The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications–posthoc analysis of two randomised clinical trials in open abdominal surgery

Background While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications. Methods Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011–2013 and 2014–2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end–expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time–weighted average dynamic driving pressure and mechanical power were calculated for individual patients. A multivariable logistic regression model adjusted for confounders was used to assess the independent associations of driving pressure and mechanical power with the occurrence of a composite of postoperative pulmonary complications, the primary endpoint of this posthoc analysis. Findings In 1191 patients included, postoperative pulmonary complications occurrence was 35.9%. Median time–weighted average driving pressure and mechanical power were 14·0 [11·0–17·0] cmH2O, and 7·6 [5·1–10·0] J/min, respectively. While driving pressure was not independently associated with postoperative pulmonary complications (odds ratio, 1·06 [95% CI 0·88–1·28]; p=0.534), the mechanical power had an independent association with the occurrence of postoperative pulmonary complications (odds ratio, 1·28 [95% CI 1·05–1·57]; p=0.016). These findings were independent of body mass index or the level of PEEP used, i.e., independent of the randomisation arm. Interpretation In this merged cohort of surgery patients, higher intraoperative mechanical power was independently associated with postoperative pulmonary complications. Mechanical power could serve as a summary ventilatory biomarker for the risk for postoperative pulmonary complications in these patients, but our findings need confirmation in other, preferably prospective studies. Funding The two original studies were supported by unrestricted grants from the European Society of Anaesthesiology and the Amsterdam University Medical Centers, Location AMC. For this current analysis, no additional funding was requested. The funding sources had neither a role in the design, collection of data, statistical analysis, interpretation of data, writing of the report, nor in the decision to submit the paper for publication