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Many physical systems characterized by nonlinear multiscale interactions can be modelled by treating unresolved degrees of freedom as random fluctuations. However, even when the microscopic governing equations and qualitative macroscopic behaviour are known, it is often difficult to derive a stochastic model that is consistent with observations. This is especially true for systems such as turbulence where the perturbations do not behave like Gaussian white noise, introducing non-Markovian behaviour to the dynamics. We address these challenges with a framework for identifying interpretable stochastic nonlinear dynamics from experimental data, using forward and adjoint Fokker–Planck equations to enforce statistical consistency. If the form of the Langevin equation is unknown, a simple sparsifying procedure can provide an appropriate functional form. We demonstrate that this method can learn stochastic models in two artificial examples: recovering a nonlinear Langevin equation forced by coloured noise and approximating the second-order dynamics of a particle in a double-well potential with the corresponding first-order bifurcation normal form. Finally, we apply Langevin regression to experimental measurements of a turbulent bluff body wake and show that the statistical behaviour of the centre of pressure can be described by the dynamics of the corresponding laminar flow driven by nonlinear state-dependent noise.

The stability and sensitivity of two- and three-dimensional global modes developing on steady spanwise-homogeneous laminar separated flows around NACA 4412 swept wings are numerically investigated for different Reynolds numbers ${\\textit {Re}}$ and angles of attack $\\alpha$. The wake dynamics is driven by the two-dimensional von Kármán mode whose emergence threshold in the $\\alpha \\unicode{x2013}{\\textit {Re}}$ plane is computed with that of the three-dimensional centrifugal mode. At the critical Reynolds number, the Strouhal number, the streamwise wavenumber of the von Kármán mode and the spanwise wavenumber of the leading three-dimensional centrifugal mode scale as a power law of $\\alpha$. The introduction of a sweep angle attenuates the growth of all unstable modes and entails a Doppler effect in the leading modes’ dynamics and a shift towards non-zero frequencies of the three-dimensional centrifugal modes. These are found to be non-dispersive as opposed to the von Kármán modes. The sensitivity of the leading global modes is investigated in the vicinity of the critical conditions through adjoint-based methods. The growth-rate sensitivity map displays a region on the suction side of the wing, wherein a streamwise-oriented force has a net stabilising effect, comparable to what could have been obtained inside the recirculation bubble. In agreement with the predictions of the sensitivity analysis, a spanwise-homogeneous force suppresses the Hopf bifurcation and stabilises the entire branch of von Kármán modes. In the limit of small amplitudes, passive control via spanwise-wavy forcing produces a stabilising effect similar to that of a spanwise-homogeneous control and is more effective than localised spherical forces.

A bstract BabyIAXO is the intermediate stage of the International Axion Observatory (IAXO) to be hosted at DESY. Its primary goal is the detection of solar axions following the axion helioscope technique. Axions are converted into photons in a large magnet that is pointing to the sun. The resulting X-rays are focused by appropriate X-ray optics and detected by sensitive low-background detectors placed at the focal spot. The aim of this article is to provide an accurate quantitative description of the different components (such as the magnet, optics, and X-ray detectors) involved in the detection of axions. Our efforts have focused on developing robust and integrated software tools to model these helioscope components, enabling future assessments of modifications or upgrades to any part of the IAXO axion helioscope and evaluating the potential impact on the experiment’s sensitivity. In this manuscript, we demonstrate the application of these tools by presenting a precise signal calculation and response analysis of BabyIAXO’s sensitivity to the axion-photon coupling. Though focusing on the Primakoff solar flux component, our virtual helioscope model can be used to test different production mechanisms, allowing for direct comparisons within a unified framework.

Critical to the mitigation of parasitic vector-borne diseases is the development of accurate spatial predictions that integrate environmental conditions conducive to pathogen proliferation. Species of Plasmodium and Trypanosoma readily infect humans, and are also common in birds. Here, we develop predictive spatial models for the prevalence of these blood parasites in the olive sunbird (Cyanomitra olivacea). Since this species exhibits high natural parasite prevalence and occupies diverse habitats in tropical Africa, it represents a distinctive ecological model system for studying vector-borne pathogens. We used PCR and microscopy to screen for haematozoa from 28 sites in Central and West Africa. Species distribution models were constructed to associate ground-based and remotely sensed environmental variables with parasite presence. We then used machine-learning algorithm models to identify relationships between parasite prevalence and environmental predictors. Finally, predictive maps were generated by projecting model outputs to geographically unsampled areas. Results indicate that for Plasmodium spp., the maximum temperature of the warmest month was most important in predicting prevalence. For Trypanosoma spp., seasonal canopy moisture variability was the most important predictor. The models presented here visualize gradients of disease prevalence, identify pathogen hotspots and will be instrumental in studying the effects of ecological change on these and other pathogens.

The restoration of CD4⁺ T cells, especially T-helper type 17 (Th17) cells, remains incomplete in the gut mucosa of most human immunodeficiency virus type 1 (HIV-1)–infected individuals despite sustained antiretroviral therapy (ART). Herein, we report an increase in the absolute number of CXCR3⁺ T cells in the duodenal mucosa during ART. The frequencies of Th1 and CXCR3⁺ CD8⁺ T cells were increased and negatively correlated with CCL20 and CCL25 expression in the mucosa. In ex vivo analyses, we showed that interferon γ, the main cytokine produced by Th1 and effector CD8⁺ T cells, downregulates the expression of CCL20 and CCL25 by small intestine enterocytes, while it increases the expression of CXCL9/10/11, the ligands of CXCR3. Interleukin 18, a pro-Th1 cytokine produced by enterocytes, also contributes to the downregulation of CCL20 expression and increases interferon γ production by Th1 cells. This could perpetuate an amplification loop for CXCR3-driven Th1 and effector CD8⁺ T cells recruitment to the gut, while impairing Th17 cells homing through the CCR6-CCL20 axis in treated HIV-1–infected individuals.

The gut CD4+ T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6–CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6+CD4+ T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3+ T regulatory (Treg) cells, specifically the CCR6− subset, was increased. The resulting imbalance in the Th17/CCR6− Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-β (TGF-β) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6+CD4+ T cells to the small intestine in treated HIV-1-infected individuals.

Pneumococcal vaccine is effective in preventing invasive pneumococcal disease in adults >or=65 years of age, but it is not widely used in Western Europe. In this study, data from an earlier (1995) cost-effectiveness study on Belgium, France, Scotland, Spain, and Sweden are updated, and data on five new countries--Denmark, the UK (specifically, England and Wales), Germany, Italy and The Netherlands--are added. Epidemiological and economic variables specific for each country were used, and it was assumed that pneumococcal and influenza vaccines would both be administered during the same physician visit. In the base-case analyses, the cost-effectiveness ratios ranged from euro 9239 to euro 23,657 per quality-adjusted life-year. Because the incidence and mortality of invasive pneumococcal disease were underestimated in most countries, a country-by-country analysis was performed, assuming an incidence of 50 cases per 100,000 population and mortality rates of 20, 30 and 40%. For a mortality of 20%, the cost-effectiveness ratios ranged from euro 4,778 to euro 17,093, and for a mortality of 30%, they ranged from euro 3,186 to euro 11,395. Pneumococcal vaccination to prevent invasive pneumococcal disease in elderly adults was very cost-effective in all 10 countries. This evidence justifies the wider use of the vaccine in Western Europe.

Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged ≥65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from ∼11,000 to ∼33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged ≥65 years.

The onset of unsteadiness in a boundary-layer flow past a cylindrical roughness element is investigated for three flow configurations at subcritical Reynolds numbers, both experimentally and numerically. On the one hand, a quasi-periodic shedding of hairpin vortices is observed for all configurations in the experiment. On the other hand, global stability analyses have revealed the existence of a varicose isolated mode, as well as of a sinuous one, both being linearly stable. Nonetheless, the isolated stable varicose modes are highly sensitive, as ascertained by pseudospectrum analysis. To investigate how these modes might influence the dynamics of the flow, an optimal forcing analysis is performed. The optimal response consists of a varicose perturbation closely related to the least stable varicose isolated eigenmode and induces dynamics similar to that observed experimentally. The quasi-resonance of such a global mode to external forcing might thus be responsible for the onset of unsteadiness at subcritical Reynolds numbers, hence providing a simple explanation for the experimental observations.

The transition to unsteadiness of a three-dimensional open cavity flow is investigated using the joint application of direct numerical simulations and fully three-dimensional linear stability analyses, providing a clear understanding of the first two bifurcations occurring in the flow. The first bifurcation is characterized by the emergence of Taylor–Görtler-like vortices resulting from a centrifugal instability of the primary vortex core. Further increasing the Reynolds number eventually triggers self-sustained periodic oscillations of the flow in the vicinity of the spanwise end walls of the cavity. This secondary instability causes the emergence of a new set of Taylor–Görtler vortices experiencing a spanwise drift directed toward the spanwise end walls of the cavity. While a two-dimensional stability analysis would fail to capture this secondary instability due to the neglect of the lateral walls, it is the first time to our knowledge that this drifting of the vortices can be entirely characterized by a three-dimensional linear stability analysis of the flow. Good agreements with experimental observations and measurements strongly support our claim that the initial stages of the transition to turbulence of three-dimensional open cavity flows are solely governed by modal instabilities.