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Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption. These metabolic changes, resembling pseudostarvation, result from the low extracellular pH rather than from the lactosis component, and render these cells dependent on autophagy for survival. Meanwhile, acetoacetate, a natural metabolite produced by the liver, is utilized by monocytes/macrophages as an alternative fuel to mitigate lactic acidosis-induced pseudostarvation, as evidenced by retained mitochondrial integrity and function, retained nutrient uptake, and survival without the need of autophagy. Our results thus show that acetoacetate may increase tissue tolerance to sustained lactic acidosis. Lactic acidosis is a metabolic state that occurs in injured tissues. Here the authors show that macrophages, in order to remain functional in acidosis, reduce their mitochondrial mass by mitophagy and rely on autophagy for survival, with mitochondrial integrity retained using acetoacetate as alternative fuel.

Arbuscular mycorrhizal fungi (AMF) play a major role in the uptake of nutrients by agricultural plants. Nevertheless, some agricultural practices can interrupt fungal-plant signaling and thus impede the establishment of the mycorrhizal symbiosis. A field experiment performed over a 5-year period demonstrated that both the absence of tillage and of nitrogen (N) fertilization improved AMF colonization of wheat roots. Moreover, under no-till conditions, N uptake and aboveground biomass production did not vary significantly between N-fertilized and N-unfertilized plots. In contrast, both N uptake and above ground biomass were much lower when N fertilizer was not added during conventional tillage. This finding strongly suggests that for wheat, no-till farming is a sustainable agricultural system that allows a gradual reduction in N fertilizer use by promoting AMF functionality and at the same time increasing N uptake.

Cardiovascular ageing is a process that begins early in life and leads to a progressive change in structure and decline in function due to accumulated damage across diverse cell types, tissues and organs contributing to multi-morbidity. Damaging biophysical, metabolic and immunological factors exceed endogenous repair mechanisms resulting in a pro-fibrotic state, cellular senescence and end-organ damage, however the genetic architecture of cardiovascular ageing is not known. Here we use machine learning approaches to quantify cardiovascular age from image-derived traits of vascular function, cardiac motion and myocardial fibrosis, as well as conduction traits from electrocardiograms, in 39,559 participants of UK Biobank. Cardiovascular ageing is found to be significantly associated with common or rare variants in genes regulating sarcomere homeostasis, myocardial immunomodulation, and tissue responses to biophysical stress. Ageing is accelerated by cardiometabolic risk factors and we also identify prescribed medications that are potential modifiers of ageing. Through large-scale modelling of ageing across multiple traits our results reveal insights into the mechanisms driving premature cardiovascular ageing and reveal potential molecular targets to attenuate age-related processes. Cardiovascular ageing is characterised by a progressive decline in function, which contributes to multi-morbidity. Here, the authors use machine learning to predict biological age and identify key genetic risk factors.

BackgroundStructural changes caused by spinal curvature may impact the organs within the thoracic cage, including the heart. Cardiac abnormalities in patients with idiopathic scoliosis are often studied post-corrective surgery or secondary to diseases. To investigate cardiac structure, function and outcomes in participants with scoliosis, phenotype and imaging data of the UK Biobank (UKB) adult population cohort were analysed.MethodsHospital episode statistics of 502 324 adults were analysed to identify participants with scoliosis. Summary 2D cardiac phenotypes from 39 559 cardiac MRI (CMR) scans were analysed alongside a 3D surface-to-surface (S2S) analysis.ResultsA total of 4095 (0.8%, 1 in 120) UKB participants were identified to have all-cause scoliosis. These participants had an increased lifetime risk of major adverse cardiovascular events (MACEs) (HR=1.45, p<0.001), driven by heart failure (HR=1.58, p<0.001) and atrial fibrillation (HR=1.54, p<0.001). Increased radial and decreased longitudinal peak diastolic strain rates were identified in participants with scoliosis (+0.29, Padj <0.05; −0.25, Padj <0.05; respectively). Cardiac compression of the top and bottom of the heart and decompression of the sides was observed through S2S analysis. Additionally, associations between scoliosis and older age, female sex, heart failure, valve disease, hypercholesterolemia, hypertension and decreased enrolment for CMR were identified.ConclusionThe spinal curvature observed in participants with scoliosis alters the movement of the heart. The association with increased MACE may have clinical implications for whether to undertake surgical correction. This work identifies, in an adult population, evidence for altered cardiac function and an increased lifetime risk of MACE in participants with scoliosis.

The optimal level of positive end–expiratory pressure (PEEP) during minimally invasive abdominal surgery is uncertain. Intraoperative ventilation with individualized high PEEP and recruitment maneuvers can be used to keep the driving pressure (ΔP) low, but can also lead to hypotension. In addition, the resulting ΔP and feasibility of individualized high PEEP in minimally invasive abdominal surgery is unclear. Planned interim analysis on safety and feasibility of ‘Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery’ (GENERATOR), an ongoing randomized clinical trial that compares individualized high PEEP, titrated to the lowest ΔP, with a standard low PEEP ventilation strategy with respect to postoperative pulmonary complications. The primary endpoint for this analysis was the proportion of patients with intraoperative hypotension. Secondary endpoints were other intraoperative complications, ventilation variables and feasibility parameters. From December 2023 to July 2024, 181 patients were enrolled. Data for analysis were available for 177 patients, of which 87 patients were randomized to individualized high PEEP and 90 to standard low PEEP. Intraoperative hypotension was similar between the individualized high PEEP vs standard low PEEP group (11.5 vs 11.1 %, relative risk ratio 1.0 [95 % CI 0.5–2.4], p = 1.00), while vasopressor use was higher in the intervention group. The median difference in ΔP between both groups was 6 cm H2O. Protocol compliance was 81.6 % in the individualized high PEEP group vs 97.8 % in the standard low PEEP group; most instances of non–compliance in the individualized high PEEP group concerned a level of PEEP that was too high. In minimally invasive abdominal surgery, a ventilation strategy using individualized high PEEP was not associated with a higher incidence of hypotension, but did show an increased use of vasopressors. The intervention was highly feasible, and led to a lower ΔP. These interim findings warrant confirmation in the main analysis of GENERATOR. This research was funded by ZonMW, grant number 10390012110091. •Individualized high PEEP ventilation is feasible in minimally invasive abdominal surgery.•Intraoperative hypotension is similar between individualized high PEEP and standard low PEEP.•Vasopressors were used in higher doses with individualized high PEEP compared to standard low PEEP.•Driving pressure was lower with individualized high PEEP compared to standard low PEEP.

Satellite imagery has the potential to monitor flooding across wide geographical regions. Recent launches have improved the spatial and temporal resolution of available data, with the European Space Agency (ESA) Copernicus programme providing global imagery at no end-user cost. Synthetic Aperture Radar (SAR) is of particular interest due to its ability to map flooding independent of weather conditions. Satellite-derived flood observations have real-world application in flood risk management and validation of hydrodynamic models. This thesis presents a workflow for estimating flood extent, depth and volume utilising ESA Sentinel-1 SAR imagery. Flood extents are extracted using a combination of change detection, variable histogram thresholding and object-based region growing. An innovative technique has been developed for estimating flood shoreline heights by combining the inundation extents with high-resolution terrain data. A grid-based framework is used to derive the water surface from the shoreline heights, from which water depth and volume are calculated. The methodology is applied to numerous catchments across the north of England that suffered from severe flooding throughout the winter of 2015-16. Extensive flooding has been identified throughout the study region, with peak inundation occurring on 29th December 2015. On this date, over 100 km2 of flooding is identified in the Ouse catchment, equating to a water volume of 0.18 km3. The SAR flood extents are validated against satellite optical imagery, achieving a Total Accuracy of 91% and a Critical Success Index of 77%. The derived water surfaces have an average error of 3 cm and an RMSE of 98 cm compared to river stage measurements. The methods developed are robust and globally applicable, shown with an additional study along the Mackenzie River in Australia. The presented methodology, alongside the increased temporal resolution provided by Sentinel-1, highlights the potential for accurate, reliable mapping of flood dynamics using satellite imagery.

Child support enforcement in the United States continues to be a serious problem, and Illinois is one of the worst examples.

The atomic Quantum Kicked Rotor (QKR) is an outstanding 'quantum simulator' for the exploration of transport in disordered quantum systems. Here we study experimentally the phase-shifted QKR, which we show to display properties close to an ideal disordered quantum system, opening new windows into the study of Anderson physics.

AbstractAnderson localization is the ubiquitous phenomenon of inhibition of transport of classical and quantum waves in a disordered medium. In dimension one, it is well known that all states are localized, implying that the distribution of an initially narrow wave packet released in a disordered potential will, at long time, decay exponentially on the scale of the localization length. However, the exact shape of the stationary localized distribution differs from a purely exponential profile and has been computed almost fifty years ago by Gogolin. Using the atomic quantum kicked rotor, a paradigmatic quantum simulator of Anderson localization physics, we study this asymptotic distribution by two complementary approaches. First, we discuss the connection of the statistical properties of the system’s localized eigenfunctions and their exponential decay with the localization length of the Gogolin distribution. Next, we make use of our experimental platform, realizing an ideal Floquet disordered system, to measure the long-time probability distribution and highlight the very good agreement with the analytical prediction compared to the purely exponential one over 3 orders of magnitude.Graphical Abstract

In patients with advanced breast cancer, switching to camizestrant with a CDK4/6 inhibitor after ESR1 -mutation detection (and before disease progression) led to significantly longer progression-free survival.