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It has recently been speculated that long-time average quantities of hyperchaotic dissipative systems may be approximated by weighted sums over unstable invariant tori embedded in the attractor, analogous to equivalent sums over periodic orbits, which are inspired by the rigorous periodic orbit theory and which have shown much promise in fluid dynamics. Using a new numerical method for converging unstable invariant two-tori in a chaotic partial differential equation (PDE), and exploiting symmetry breaking of relative periodic orbits to detect those tori, we identify many quasiperiodic, unstable, invariant two-torus solutions of a modified Kuramoto-Sivashinsky equation. The set of tori covers significant parts of the chaotic attractor and weighted averages of the properties of the tori-with weights computed based on their respective stability eigenvalues-approximate average quantities for the chaotic dynamics. These results are a step toward exploiting higher-dimensional invariant sets to describe general hyperchaotic systems, including dissipative spatiotemporally chaotic PDEs., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

One approach for describing spatiotemporal chaos is to study the unstable invariant sets embedded in the chaotic attractor of the system. While equilibria, periodic orbits, and invariant tori can be computed using existing methods, the numerical identification of heteroclinic and homoclinic connections between them remains challenging. We propose a robust matrix-free variational method for computing connecting orbits between equilibrium solutions. Instead of a common shooting-based approach, we view the identification of a connecting orbit as a minimization problem in the space of smooth curves in the state space that connect the two equilibria. In this approach, the deviation of a connecting curve from an integral curve of the vector field is penalized by a non-negative cost function. Minimization of the cost function deforms a trial curve until, at a global minimum, a connecting orbit is obtained. The method has no limitation on the dimension of the unstable manifold at the origin equilibrium and does not suffer from exponential error amplification associated with time-marching a chaotic system. Owing to adjoint-based minimization techniques, no Jacobian matrices need to be constructed. Therefore, the memory requirement scales linearly with the size of the problem, allowing the method to be applied to high-dimensional dynamical systems. The robustness of the method is demonstrated for the one-dimensional Kuramoto-Sivashinsky equation., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Swine manure has a high load of pathogens, which can pose a risk to human and environmental health. In Brazil, studies evaluating the survival of pathogens in soil are scarce. Therefore, this study aimed to evaluate the survival, percolation, and leaching of enterobacteria in clayey soil after fertilization with swine manure. For this purpose, soil columns were fertilized with manure spiked with enterobacteria. The microorganisms' behavior was monitored in terms of survival, percolation, and leaching with and without rain. Soil samples were collected, and Escherichia coli and Salmonella enterica serovar Senftemberg were quantified. The results indicated that E. coli survived for a longer period (43 days) than S. senftemberg (14 days). E. coli percolated quickly through the soil, leaching 60 cm in less than 5 min during rainy events and remaining viable for up to 24 h after the rain. The results show the importance of treating manure effectively before being added to the soil. An efficient treatment could be anaerobic digestion, followed by a pond system. Considering the characteristics of swine-producing regions, the load of effluents applied to the soil may percolate, leach, or run off and consequently contaminate water bodies with pathogens.

One approach to understand the chaotic dynamics of nonlinear dissipative systems is the study of non-chaotic yet dynamically unstable invariant solutions embedded in the system's chaotic attractor. The significance of zero-dimensional unstable fixed points and one-dimensional unstable periodic orbits capturing time-periodic dynamics is widely accepted for high-dimensional chaotic systems, including fluid turbulence, while higher-dimensional invariant tori representing quasiperiodic dynamics have rarely been considered. We demonstrate that unstable 2-tori are generically embedded in the hyperchaotic attractor of a dissipative system of ordinary differential equations; tori can be numerically identified via bifurcations of unstable periodic orbits and their parameteric continuation and characterization of stability properties are feasible. As higher-dimensional tori are expected to be structurally unstable, 2-tori together with periodic orbits and equilibria form a complete set of relevant invariant solutions on which to base a dynamical description of chaos.

Accurate segmentation of cerebral venous vasculature from gradient echo data is of central importance in several areas of neuroimaging such as for the susceptibility-based assessment of brain oxygenation or planning of electrode placement in deep brain stimulation. In this study, a vein segmentation algorithm for single- and multi-echo gradient echo data is proposed. First, susceptibility maps, true susceptibility-weighted images, and, in the multi-echo case, R 2 * maps were generated from the gradient echo data. These maps were filtered with an inverted Hamming filter to suppress background contrast as well as artifacts from field inhomogeneities at the brain boundaries. A shearlet-based scale-wise representation was generated to calculate a vesselness function and to generate segmentations based on local thresholding. The accuracy of the proposed algorithm was evaluated for different echo times and image resolutions using a manually generated reference segmentation and two vein segmentation algorithms (Frangi vesselness-based, recursive vesselness filter) as a reference with the Dice and Cohen's coefficients as well as the modified Hausdorff distance. The Frangi-based and recursive vesselness filter methods were significantly outperformed with regard to all error metrics. Applying the algorithm, susceptibility differences likely related to differences in blood oxygenation between superficial and deep venous territories could be demonstrated., Competing Interests: Declaration of Competing Interest None of the authors has any competing interests to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Chaotic dynamics in systems ranging from low-dimensional nonlinear differential equations to high-dimensional spatiotemporal systems including fluid turbulence is supported by nonchaotic, exactly recurring time-periodic solutions of the governing equations. These unstable periodic orbits capture key features of the turbulent dynamics and sufficiently large sets of orbits promise a framework to predict the statistics of the chaotic flow. Computing periodic orbits for high-dimensional spatiotemporally chaotic systems remains challenging as known methods either show poor convergence properties because they are based on time-marching of a chaotic system causing exponential error amplification, or they require constructing Jacobian matrices which is prohibitively expensive. We propose a new matrix-free method that is unaffected by exponential error amplification, is globally convergent, and can be applied to high-dimensional systems. The adjoint-based variational method constructs an initial value problem in the space of closed loops such that periodic orbits are attracting fixed points for the loop dynamics. We introduce the method for general autonomous systems. An implementation for the one-dimensional Kuramoto-Sivashinsky equation demonstrates the robust convergence of periodic orbits underlying spatiotemporal chaos. Convergence does not require accurate initial guesses and is independent of the period of the respective orbit.

Faces undergo massive changes over time and life events. We need a mental representation which is flexible enough to cope with the existing visual varieties, but which is also stable enough to be the basis for valid recognition. Two main theoretical frameworks exist to describe facial representations: prototype models assuming one central item comprising all visual experiences of a face, and exemplar models assuming single representations of each visual experience of a face. We introduce a much more ecological valid model dealing with episodic prototypes (the Episodic Prototypes Model-EPM), where faces are represented by a low number of prototypes that refer to specific Episodes of Life (EoL, e.g., early adulthood, mature age) during which the facial appearance shows only moderate variation. Such an episodic view of mental representation allows for efficient storage, as the number of needed prototypes is relatively low, and it allows for the needed variation within a prototype that keeps the everyday and steadily ongoing changes across a certain period of time. Studies 1-3 provide evidence that facial representations are highly dependent on temporal aspects which is in accord with EoL, and that individual learning history generates the structure and content of respective prototypes. In Study 4, we used implicit measures (RT) in a face verification task to investigate the postulated power of the EPM. We could demonstrate that episodic prototypes clearly outperformed visual depictions of exhaustive prototypes, supporting the general idea of our approach., Competing Interests: Declaration of Conflicting Interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objectives To characterize subcortical nuclei by multi-parametric quantitative magnetic resonance imaging. Materials and Methods: The following quantitative multiparametric MR data of five healthy volunteers were acquired on a 7T MRI system: 3D gradient echo (GRE) data for the calculation of quantitative susceptibility maps (QSM), GRE sequences with and without off-resonant magnetic transfer pulse for magnetization transfer ratio (MTR) calculation, a magnetization-prepared 2 rapid acquisition gradient echo sequence for T 1 mapping, and (after a coil change) a density-adapted 3D radial pulse sequence for 23 Na imaging. First, all data were co-registered to the GRE data, volumes of interest (VOIs) for 21 subcortical structures were drawn manually for each volunteer, and a combined voxel-wise analysis of the four MR contrasts (QSM, MTR, T 1 , 23 Na) in each structure was conducted to assess the quantitative, MR value-based differentiability of structures. Second, a machine learning algorithm based on random forests was trained to automatically classify the groups of multi-parametric voxel values from each VOI according to their association to one of the 21 subcortical structures. Results The analysis of the integrated multimodal visualization of quantitative MR values in each structure yielded a successful classification among nuclei of the ascending reticular activation system (ARAS), the limbic system and the extrapyramidal system, while classification among (epi-)thalamic nuclei was less successful. The machine learning-based approach facilitated quantitative MR value-based structure classification especially in the group of extrapyramidal nuclei and reached an overall accuracy of 85% regarding all selected nuclei. Conclusion Multimodal quantitative MR enabled excellent differentiation of a wide spectrum of subcortical nuclei with reasonable accuracy and may thus enable sensitive detection of disease and nucleus-specific MR-based contrast alterations in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schneider, Ma, Wagner, Behl, Nagel, Ladd, Heiland, Bendszus and Straub.)

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the APOL1 , NAT2 , and YEATS4 genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus; 2. actionability; 3. context-sensitive triggers; 4. workflow integration; 5. feasibility; 6. interpretability; 7. portability; and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for APOL1 , NAT2 , and YEATS4 was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS.

Viral transmission pathways have profound implications for public safety; it is thus imperative to establish a complete understanding of viable infectious avenues. Mounting evidence suggests SARS-CoV-2 can be transmitted via the air; however, this has not yet been demonstrated. Here we quantitatively analyze virion accumulation by accounting for aerosolized virion emission and destabilization. Reported superspreading events analyzed within this framework point towards aerosol mediated transmission of SARS-CoV-2. Virion exposure calculated for these events is found to trace out a single value, suggesting a universal minimum infective dose (MID) via aerosol that is comparable to the MIDs measured for other respiratory viruses; thus, the consistent infectious exposure levels and their commensurability to known aerosol-MIDs establishes the plausibility of aerosol transmission of SARS-CoV-2. Using filtration at a rate exceeding the destabilization rate of aerosolized SARS-CoV-2 can reduce exposure below this infective dose.

From soda cans to space rockets, thin-walled cylindrical shells are abundant, offering exceptional load carrying capacity at relatively low weight. However, the actual load at which any shell buckles and collapses is very sensitive to imperceptible defects and cannot be predicted, which challenges the of such structures. Consequently, probabilistic descriptions in terms of empirical design rules are used and designing reliable structures requires the use of conservative strength estimates. We introduce a nonlinear description where finite-amplitude perturbations trigger buckling. Drawing from the analogy between imperfect shells which buckle and imperfect pipe flow which becomes turbulent, we experimentally show that lateral probing of cylindrical shells reveals their strength nondestructively. A new ridge-tracking method is applied to commercial cylinders with a hole showing that when the location where buckling nucleates is known we can accurately predict the buckling load of each individual shell, within ±5%. Our study provides a new promising framework to understand shell buckling, and more generally, imperfection-sensitive instabilities.

Objectives: The aim of this study was to explore blood deoxygenation across cerebral arteriovenous malformations (AVMs) for functional characterization of AVM vasculature., Materials and Methods: Fifteen patients with cerebral arteriovenous vascular malformation were prospectively studied by digital subtraction angiography and using a 3 T magnetic resonance imaging system, with which three-dimensional (3D) gradient echo data for the calculation of quantitative susceptibility maps, velocity-encoded 3D gradient echo data for 3D flow assessment, and contrast-enhanced 3D time-of-flight data were acquired.The nidus, major supplying artery, and major draining veins were identified on digital subtraction angiography, and volumes of interest of the AVM nidus, AVM-related inflow and outflow vessels, and non-AVM-related normal veins were drawn on coregistered contrast-enhanced 3D time-of-flight data. The resulting volumes of interest were applied to quantitative susceptibility mapping and flow data., Results: All patients showed a significant stepwise increase in susceptibility between feeding artery and nidus as well as between nidus and draining vein (Padjusted = 0.035, Padjusted= 0.007, respectively). Results revealed between 9.3% and 50.9% of the normal transcapillary blood deoxygenation-related susceptibility change between the feeding artery and the draining vein of the AVMs. When normalized by nidal blood flow velocity, this change was correlated with the presence of perinidal blood products. The mean susceptibility change across cerebral AVMs normalized with nidal volume inversely correlated with mean nidal flow velocity., Conclusions: Susceptibility changes indicating blood deoxygenation across cerebral AVMs were shown for the first time in this study and were associated with the presence of perinidal blood products. Deoxygenation measures may serve as functional characterization of AVM vasculature and may offer the potential for individual treatment assessment and possible risk stratification.

Purpose: To quantify the influence of melanin content on magnetic susceptibility of cerebral melanoma metastases., Methods: Patients with non-hemorrhagic metastases were included based on the absence of susceptibility blooming artifacts. Susceptibility maps were calculated from 3D gradient echo data, using Laplacian-based phase unwrapping, sophisticated harmonic artefact reduction for phase data (V-SHARP) with varying spherical kernel sizes for background field removal and the iLSQR algorithm for the inversion of phase data. Susceptibility maps were referenced to cerebrospinal fluid. Non-hemorrhagic metastases were identified on contrast-enhanced T1-weighted images and susceptibility weighted images. Metastases masks were drawn on T1-weighted post-contrast images and used to compute mean susceptibility values of each metastasis., Results: A total of 33 non-hemorrhagic melanoma brain metastases in 20 patients were quantitatively evaluated. Metastases without and with hyperintense signal on T1-weighted images, which corresponds to the melanin content, showed median susceptibility values of -0.028 ppm and -0.020 ppm, respectively. The susceptibility differences between metastases without and with T1-weighted hyperintense signal was not statistically significant (p ≥ 0.05)., Conclusion: Non-hemorrhagic cerebral melanoma metastases showed weak diamagnetic susceptibility values and susceptibility did not significantly correlate to T1-weighted signals. Therefore, melanin does not seem to be a major contributor to susceptibility in cerebral melanoma metastases.

Biological filaments driven by molecular motors tend to experience tangential propulsive forces also known as active follower forces. When such a filament encounters an obstacle, it deforms, which reorients its follower forces and alters its entire motion. If the filament pushes a cargo, the friction on the cargo can be enough to deform the filament, thus affecting the transport properties of the cargo. Motivated by cytoskeletal filament motility assays, we study the dynamic buckling instabilities of a two-dimensional slender elastic filament driven through a dissipative medium by tangential propulsive forces in the presence of obstacles or cargo. We observe two distinct instabilities. When the filament's head is pinned or experiences significant translational but little rotational drag from its cargo, it buckles into a steadily rotating coiled state. When it is clamped or experiences both significant translational and rotational drag from its cargo, it buckles into a periodically beating, overall translating state. Using minimal analytically tractable models, linear stability theory and fully nonlinear computations, we study the onset of each buckling instability, characterize each buckled state, and map out the phase diagram of the system. Finally, we use particle-based Brownian dynamics simulations to show our main results are robust to moderate noise and steric repulsion. Overall, our results provide a unified framework to understand the dynamics of tangentially propelled filaments and filament-cargo assemblies.

The insect odorant receptors (ORs) are amongst the largest gene families in insect genomes and the primary means by which insects recognize volatile compounds. The evolution of ORs is thus instrumental in explaining the chemical ecology of insects and as a model of evolutionary biology. However, although ORs have been described from numerous insect species, their analysis within and amongst the insect orders has been hindered by a combination of limited genomic information and a tendency of the OR family toward rapid divergence, gain, and loss. We addressed these issues in the insect order Coleoptera through a targeted genomic annotation effort that included 1181 ORs from one species of the sister order Strepsiptera and 10 species representing the four coleopteran suborders. The numbers of ORs in each species varied from hundreds to fewer than 10, but coleopteran ORs could nevertheless be represented within a scheme of nine monophyletic subfamilies. We observed many radiations and losses of genes amongst OR subfamilies, and the diversity of ORs appeared to parallel the host breadth of the study species. However, some small lineages of ORs persisted amongst many coleopteran families, suggesting receptors of key function that underlie the olfactory ecology of beetles., (© 2019 The Royal Entomological Society.)

Spatially localized invariant solutions of plane Couette flow are organized in a snakes-and-ladders structure strikingly similar to that observed for simpler pattern-forming partial differential equations [Schneider, Gibson, and Burke, Phys. Rev. Lett. 104, 104501 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.104501]. We demonstrate the mechanism by which these snaking solutions originate from well-known periodic states of the Taylor-Couette system. They are formed by a localized slug of wavy-vortex flow that emerges from a background of Taylor vortices via a modulational sideband instability. This mechanism suggests a close connection between pattern-formation theory and Navier-Stokes flow.

The high-throughput selection of individual droplets is an essential function in droplet-based microfluidics. Fluorescence-activated droplet sorting is achieved using electric fields triggered at rates up to 30 kHz, providing the ultra-high throughput relevant in applications where large libraries of compounds or cells must be analyzed. To achieve such sorting frequencies, electrodes have to create an electric field distribution that generates maximal actuating forces on the droplet while limiting the induced droplet deformation and avoid disintegration. We propose a metric characterizing the performance of an electrode design relative to the theoretical optimum and analyze existing devices using full 3D simulations of the electric fields. By combining parameter optimization with numerical simulation we derive rational design guidelines and propose optimized electrode configurations. When tested experimentally, the optimized design show significantly better performance than the standard designs.

Wall-bounded shear flows transitioning to turbulence may self-organize into alternating turbulent and laminar regions forming a stripe pattern with non-trivial oblique orientation. Different experiments and flow simulations identify oblique stripe patterns as the preferred solution of the well-known Navier-Stokes equations, but the origin of stripes and their oblique orientation remains unexplained. In concluding his lectures, Feynman highlights the unexplained stripe pattern hidden in the solution space of the Navier-Stokes equations as an example demonstrating the need for improved theoretical tools to analyze the fluid flow equations. Here we exploit dynamical systems methods and demonstrate the existence of an exact equilibrium solution of the fully nonlinear 3D Navier-Stokes equations that resembles oblique stripe patterns in plane Couette flow. The stripe equilibrium emerges from the well-studied Nagata equilibrium and exists only for a limited range of pattern angles. This suggests a mechanism selecting the non-trivial oblique orientation angle of turbulent-laminar stripes.

Fluorescence-activated droplet sorting (FADS) is one of the most important features provided by droplet-based microfluidics. However, to date, it does not allow to compete with the high-throughput multiplexed sorting capabilities offered by flow cytometery. Here, we demonstrate the use of a dielectrophoretic-based FADS, allowing to sort up to five different droplet populations simultaneously. Our system provides means to select droplets of different phenotypes in a single experimental run to separate initially heterogeneous populations. Our experimental results are rationalized with the help of a numerical model of the actuation of droplets in electric fields providing guidelines for the prediction of sorting designs for upscaled or downscaled microsystems., Competing Interests: The authors declare that they have no conflict of interest.

Blood clotting is a fundamental biochemical process in post-hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T 1 - and T 2 -weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T 1 - and T 2 -weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging-based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T 1 - and T 2 -weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood-filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T 1 - and T 2 -weighted sequences, a three-dimensional (3D) gradient echo sequence and a density-adapted 3D radial projection reconstruction pulse sequence for 23 Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion-selective electrode method, respectively, in separate heparinized whole-blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage., (Copyright © 2018 John Wiley & Sons, Ltd.)

We measure the response of cylindrical shells to poking and identify a stability landscape, which fully characterizes the stability of perfect shells and imperfect ones in the case where a single defect dominates. We show that the landscape of stability is independent of the loading protocol and the poker geometry. Our results suggest that the complex stability of shells reduces to a low dimensional description. Tracking ridges and valleys of this landscape defines a natural phase-space coordinates for describing the stability of shells.

Objectives: Haemodynamically stable patients admitted for coronary artery bypass grafting in acute myocardial infarction often undergo delayed surgery in order to avoid the risks of emergency surgery. However, initially stable patients undergoing delayed surgery may develop low cardiac output syndrome (LCOS) during the waiting period, which might be a major drawback of this strategy. We aim to define risk factors and clinical consequences of LCOS during the waiting period., Methods: A total of 530 consecutive patients with acute myocardial infarction (33% non-ST-segment elevation myocardial infarction and 67% ST-segment-elevation myocardial infarction) underwent isolated coronary artery bypass grafting between 2008 and 2013. Outcomes after either immediate (<48 h after onset of symptoms) or delayed (>48 h after onset of symptoms) therapy were compared. Predictors of preoperative development of LCOS were identified using multivariate regression analysis., Results: Of the 327 patients undergoing delayed therapy, 39 (12%) developed preoperative LCOS, resulting in increased mortality compared with patients who remained stable (21 vs 7.6%, P < 0.001). Immediate therapy resulted in similar mortality compared with delayed therapy (6.4 vs 7.6%; P = 0.68) and better 7-year survival (70 vs 55%; P < 0.001). Predictors of developing LCOS were reduced left ventricular function (odds ratio 4.4), renal impairment (odds ratio 3.0), acute pulmonary infection (odds ratio 3.4) and the extent of troponin elevation at admission (odds ratio 1.01 per increase by 1 µg/l)., Conclusions: In patients with acute myocardial infarction undergoing delayed coronary artery bypass grafting, preoperative LCOS is a relevant and dangerous condition that can be avoided by operating immediately or by carefully selecting patients to be delayed according to the risk parameters identified preoperatively., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We compute nonlinear force equilibrium solutions for a clamped thin cylindrical shell under axial compression. The equilibrium solutions are dynamically unstable and located on the stability boundary of the unbuckled state. A fully localized single dimple deformation is identified as the edge state -the attractor for the dynamics restricted to the stability boundary. Under variation of the axial load, the single dimple undergoes homoclinic snaking in the azimuthal direction, creating states with multiple dimples arranged around the central circumference. Once the circumference is completely filled with a ring of dimples, snaking in the axial direction leads to further growth of the dimple pattern. These fully nonlinear solutions embedded in the stability boundary of the unbuckled state constitute critical shape deformations. The solutions may thus be a step towards explaining when the buckling and subsequent collapse of an axially loaded cylinder shell is triggered., Competing Interests: We declare we have no competing interests.

Purpose: Since quantitative susceptibility mapping (QSM) quantifies magnetic susceptibility relative to a reference value, a suitable reference tissue has to be available to compare different subjects and stages of disease., Methods: To find such a suitable reference tissue for QSM of the brain, melanoma patients with and without brain metastases were measured. Twelve reference regions were chosen and assessed for stability of susceptibility values with respect to multiple intra-individual and inter-individual measurements, age, and stage of disease., Results: Cerebrospinal fluid (CSF), the internal capsule and one region in the splenium of the corpus callosum are the regions with the smallest standard deviations of the mean susceptibility value. The mean susceptibility is 0.010 ± 0.014 ppm for CSF in the atrium of the lateral ventricles (csf post ), -0.060 ± 0.019 ppm for the posterior limb of the internal capsule (ci2), and -0.008 ± 0.019 ppm for the splenium of the corpus callosum. csf post and ci2 show nearly no dependence on age or stage of disease, whereas some other regions, e.g., the red nucleus, show moderate dependence on age or disease., Conclusion: The internal capsule and CSF appear to be the most suitable reference regions for QSM of the brain in the melanoma patients studied. Both showed virtually no dependence on age or disease and small variations among patients. Magn Reson Med 78:204-214, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Taking selfies is now becoming a standard human habit. However, as a social phenomenon, research is still in the fledgling stage and the scientific framework is sparse. Selfies allow us to share social information with others in a compact format. Furthermore, we are able to control important photographic and compositional aspects, such as perspective, which have a strong impact on the assessment of a face (e.g., demonstrated by the height-weight illusion, effects of gaze direction, faceism-index). In Study 1, we focused on the impact of perspective (left/right hemiface, above/below vs. frontal presentation) on higher cognitive variables and let 172 participants rate the perceived attractiveness, helpfulness, sympathy, dominance, distinctiveness, and intelligence, plus important information on health issues (e.g., body weight), on the basis of 14 3D faces. We could show that lateral snapshots yielded higher ratings for attractiveness compared to the classical frontal view. However, this effect was more pronounced for left hemifaces and especially female faces. Compared to the frontal condition, 30° right hemifaces were rated as more helpful, but only for female faces while faces viewed from above were perceived as significant less helpful. Direct comparison between left vs. right hemifaces revealed no effect. Relating to sympathy, we only found a significant effect for 30° right male hemifaces, but only in comparison to the frontal condition. Furthermore, female 30° right hemifaces were perceived as more intelligent. Relating to body weight, we replicated the so-called "height-weight illusion." Other variables remained unaffected. In Study 2, we investigated the impact of a typical selfie-style condition by presenting the respective faces from a lateral (left/right) and tilted (lower/higher) vantage point. Most importantly, depending on what persons wish to express with a selfie, a systematic change of perspective can strongly optimize their message; e.g., increasing their attractiveness by shooting from above left, and in contrast, decreasing their expressed helpfulness by shooting from below. We could further extent past findings relating to the height-weight illusion and showed that an additional rotation of the camera positively affected the perception of body weight (lower body weight). We discuss potential explanations for perspective-related effects, especially gender-related ones.

Purpose: Characterized by a progressive onset of gait disturbances, dementia, and urinary incontinence, idiopathic normal pressure hydrocephalus (iNPH) is considered a rare, but under-diagnosed disease. Non-invasive diagnostic markers are still insufficient to enable the diagnosis of iNPH with certainty and yet early treatment with ventriculoperitoneal (VP) shunting can reverse symptoms and stop disease progression. Vascular circulation abnormalities in iNPH may be reflected by changes in subfoveal and peripapillary choroidal thickness (PPChT). This study uses spectral domain-optical coherence tomography (SD-OCT)-based measures of retinal and choroidal thickness to test this hypothesis and to assess ophthalmological non-invasive markers for iNPH., Methods: Twelve patients who displayed neurological and neuroradiological characteristics of iNPH were subject to a full ophthalmological examination including enhanced depth imaging (EDI) SD-OCT. Of the 12 included iNPH patients, 6 had undergone VP shunting with beneficial outcome. Parameters studied with EDI SD-OCT were macular retinal thickness (MT), subfoveal choroidal thickness (SFChT), retinal nerve fiber layer thickness (RNFL), and PPChT. Results were compared with 13 healthy, age-matched controls., Results: Macular thickness and RNFL and MT values of iNPH patients did not reflect atrophy. Non-shunted iNPH patients showed significantly lowered median PPChT and SFChT values compared to healthy controls. Shunted iNPH patients displayed a significantly higher median PPChT and SFChT compared to non-shunted iNPH patients. SFChT and PPChT values in shunted patients were not significantly different to values in healthy controls., Conclusion: Although limited by small sample size, SD-OCT measures in this study reveal significant changes of choroidal thickness and support the hypothesis of choroidal susceptibility to hemodynamic alterations in iNPH. Non-shunted iNPH patients in this study show choroidal thinning in combination with normal RNFL and MT values. In addition to neurological and neuroradiological exams, this pattern may aid in the challenging diagnosis of iNPH.

Background: The pallidofugal and striatonigral fiber tracts form a functional part of the basal ganglionic neuronal networks. For deep brain stimulation, a surgical procedure applied in the treatment of Parkinson disease and dystonia, precise localization of pallidofugal pathways may be of particular clinical relevance for correct electrode positioning., Objective: To investigate whether the pallidofugal and striatonigral pathways can be visualized with magnetic resonance imaging in vivo by exploiting their intrinsic magnetic susceptibility., Methods: Three-dimensional gradient-echo imaging of 5 volunteers was performed on a 7 T magnetic resonance imaging system. To demonstrate that the displayed tubular structures in the vicinity of the subthalamic nucleus and substantia nigra truly represent fiber tracts rather than veins, gradient-echo data of a formalin-fixated brain and a volunteer during inhalation of ambient air and carbogen were collected at 3 T. Susceptibility weighted images, quantitative susceptibility maps, and effective transverse relaxation maps were reconstructed and the depiction of fiber tracts was qualitatively assessed., Results: High-resolution susceptibility-based magnetic resonance imaging contrasts enabled visualization of pallidofugal and striatonigral fiber tracts noninvasively at 3 T and 7 T. We verified that the stripe-like pattern observed on susceptibility-sensitive images is not caused by veins crossing the internal capsule but by fiber tracts traversing the internal capsule., Conclusion: Pallidofugal and striatonigral fiber tracts have been visualized in vivo for the first time by using susceptibility-sensitive image contrasts. Considering the course of pallidofugal pathways, in particular for deep brain stimulation procedures in the vicinity of the subthalamic nucleus, could provide landmarks for optimal targeting during stereotactic planning.

Next-generation sequencing is becoming increasingly common in clinical laboratories worldwide and is revolutionizing clinical molecular testing. However, the large amounts of raw data produced by next-generation sequencing assays and the need for complex bioinformatics analyses present unique challenges. Proficiency testing in clinical laboratories has traditionally been designed to evaluate assays in their entirety; however, it can be alternatively applied to separate assay components. We developed and implemented a multi-institutional proficiency testing approach to directly assess custom bioinformatics and variant interpretation processes. Six clinical laboratories, all of which use the same commercial library preparation kit for next-generation sequencing analysis of tumor specimens, each submitted raw data (FASTQ files) from four samples. These 24 file sets were then deidentified and redistributed to five of the institutions for analysis and interpretation according to their clinically validated approach. Among the laboratories, there was a high rate of concordance in the calling of single-nucleotide variants, in particular those we considered clinically significant (100% concordance). However, there was significant discordance in the calling of clinically significant insertions/deletions, with only two of seven being called by all participating laboratories. Missed calls were addressed by each laboratory to improve their bioinformatics processes. Thus, through our alternative proficiency testing approach, we identified the bioinformatic detection of insertions/deletions as an area of particular concern for clinical laboratories performing next-generation sequencing testing., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines., (Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Aim: To describe the case of a patient with a severe head injury at a depth of about 1000 m from the cave entrance in Bavaria, Germany, who received pre-hospital trauma care for 12 days until evacuation., Results: Search and rescue (SAR) operation involved 728 rescuers, 202 working directly in the cave (for a total of 9239 h) and 7 physicians from five countries. At 6-month follow-up, the patient had recovered completely and resumed his job., Conclusion: This case highlights several pitfalls of trauma care in complex SAR operations, which often rely on expert knowledge and are not yet evidence-based practice., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

When a fluid-immersed array of supported plates or pillars is dried, evaporation leads to the formation of menisci on the tips of the plates or pillars that bring them together to form complex patterns. Building on prior experimental observations, we use a combination of theory and computation to understand the nature of this instability and its evolution in both the two- and three-dimensional setting of the problem. For the case of plates, we explicitly derive the interaction torques based on the relevant physical parameters associated with pillar deformation, contact-line pinning/depinning and fluid volume changes. A Bloch-wave analysis for our periodic mechanical system captures the window of volumes where the two-plate eigenvalue characterizes the onset of the coalescence instability. We then study the evolution of these binary clusters and their eventual elastic arrest using numerical simulations that account for evaporative dynamics coupled to capillary coalescence. This explains both the formation of hierarchical clusters and the sensitive dependence of the final structures on initial perturbations, as seen in our experiments. We then generalize our analysis to treat the problem of pillar collapse in three dimensions, where the fluid domain is completely connected and the interface is a minimal surface with the uniform mean curvature. Our theory and simulations capture the salient features of experimental observations in a range of different situations and may thus be useful in controlling the ensuing patterns.

Objective: The histopathology of peripheral arterial disease and the accompanying calcification are poorly defined, and it is not known whether this varies according to different risk factors., Approach and Results: Sections from 176 upper and lower leg arteries were examined histologically in specimens from amputations of 60 patients with peripheral arterial disease, of whom 58% had diabetes mellitus, 35% had end-stage renal disease, and 48% had a history of smoking. The most common findings were calcification of the media (72% of arteries) and intimal thickening without lipid (68% of arteries), with the presence of atheromas in only 23% of arteries. Intimal calcification occurred in 43% and was generally much less extensive than medial calcification. Nonatheromatous intimal thickening was frequently severe, resulting in complete occlusion in some vessels. The absence of lipid and macrophages was confirmed by staining with oil red O and staining for CD68. Other than a greater prevalence and severity of medial calcification in end-stage renal disease, the findings did not differ between diabetics, patients with end-stage renal disease, or smokers., Conclusions: The results indicate that the majority of arteries in patients with peripheral arterial disease have a vascular lesion that is distinct from atherosclerosis, suggesting a different pathogenesis. This pattern does not differ substantially between patients with different risk factors for peripheral arterial disease. The bulk of vascular calcification in the lower extremities is medial rather than intimal., (© 2014 American Heart Association, Inc.)

Intraductal carcinoma of the prostate is a growth pattern of prostatic adenocarcinoma that has not been well characterized from the molecular standpoint. It remains debatable whether intraductal carcinoma of the prostate represents colonization of benign glands by pre-existing conventional prostatic adenocarcinoma, or progression of high-grade prostatic intraepithelial neoplasia. TMPRSS2-ERG is the most common gene fusion in conventional prostatic adenocarcinoma, identified in about 40-70% of cases. In this study, we compared the expression of ERG in intraductal carcinoma of the prostate and adjacent conventional prostatic adenocarcinoma. Thirty-one confirmed cases of intraductal carcinoma of the prostate, with adjacent conventional prostatic adenocarcinoma and available tissue blocks, were identified at our institution. Immunohistochemical stains were performed for ERG using a rabbit anti-ERG monoclonal antibody. The ERG expression in the intraductal carcinoma of the prostate component was compared with that in the adjacent conventional prostatic adenocarcinoma. Mean patient age was 65 years (range: 48-79 years). Positive ERG expression was identified in 11/31 (35%) cases of intraductal carcinoma of the prostate. In all 11/11 (100%) cases with positive ERG expression in the intraductal carcinoma of the prostate component, ERG expression was also positive in the adjacent conventional prostatic adenocarcinoma. In the 20/31 cases with negative ERG expression in the intraductal carcinoma of the prostate component, ERG was also negative in the adjacent conventional prostatic adenocarcinoma. It is highly conceivable that based on the identical ERG expression (positive or negative) in intraductal carcinoma of the prostate and the adjacent conventional prostatic adenocarcinoma, intraductal carcinoma of the prostate most likely represents colonization of benign glands by adjacent pre-existing conventional prostatic adenocarcinoma.

In linearly stable shear flows, turbulence spontaneously decays with a characteristic lifetime that varies with Reynolds number. The lifetime sharply increases with Reynolds number so that a possible divergence marking the transition to sustained turbulence at a critical point has been discussed. We present a mechanism by which the lifetimes increase: in the system's state space, turbulent motion is supported by a chaotic saddle. Inside this saddle a locally attracting periodic orbit is created and undergoes a traditional bifurcation sequence generating chaos. The formed new "turbulent bubble" is initially an attractor supporting persistent chaotic dynamics. Soon after its creation, it collides with its own boundary, by which it becomes leaky and dynamically connected with the surrounding structures. The complexity of the chaotic saddle that supports transient turbulence hence increases by incorporating the remnant of a new bubble. As a a result, the time it takes for a trajectory to leave the saddle and decay to the laminar state is increased. We demonstrate this phenomenon in plane Couette flow and show that characteristic lifetimes vary nonsmoothly and nonmonotonically with Reynolds number.

Background: Deep brain stimulation (DBS) has recently been discussed as a promising treatment option for severe cases of major depression. Experimental data have suggested that the lateral habenular complex (LHb-c) is a central region of depression-related neuronal circuits. Because of its location close to the midline, stereotactic targeting of the LHb-c presents surgeons with distinct challenges., Objective: To define the obstacles of DBS surgery for stimulation of the LHb-c and thus to establish safe trajectories., Methods: Stereotactic magnetic resonance imaging data sets of 54 hemispheres originating from 27 DBS patients were taken for analysis on a stereotactic planning workstation. After alignment of images according to the anterior commissure--posterior commissure definition, analyses focused on vessels and enlarged ventricles interfering with trajectories., Results: As major trajectory obstacles, enlarged ventricles and an interfering superior thalamic vein were found. A standard frontal trajectory (angle > 40° relative to the anterior commissure--posterior commissure in sagittal images) for bilateral stimulation was safely applicable in 48% of patients, whereas a steeper frontal trajectory (angle <40 relative to the anterior commissure--posterior commissure in sagittal images) for bilateral stimulation was possible in 96%. Taken together, safe bilateral targeting of the LHb-c was possible in 98% of all patients., Conclusion: Targeting LHb-c is a feasible and safe technique in the majority of patients undergoing surgery for DBS. However, meticulous individual planning to avoid interference with ventricles and thalamus-related veins is mandatory because an alternative steep frontal entry point has to be considered in about half of the patients.

Being able to exploit features of the human face to predict health and fitness can serve as an evolutionary advantage. Surface features such as facial symmetry, averageness, and skin colour are known to influence attractiveness. We sought to determine whether observers are able to extract more complex features, namely body weight. If possible, it could be used as a predictor for health and fitness. For instance, facial adiposity could be taken to indicate a cardiovascular challenge or proneness to infections. Observers seem to be able to glean body weight information from frontal views of a face. Is weight estimation robust across different viewing angles? We showed that participants strongly overestimated body weight for faces photographed from a lower vantage point while underestimating it for faces photographed from a higher vantage point. The perspective distortions of simple facial measures (e.g., width-to-height ratio) that accompany changes in vantage point do not suffice to predict body weight. Instead, more complex patterns must be involved in the height-weight illusion.

Sequencing by Hybridization (SBH) reconstructs an n-long target DNA sequence from its biochemically determined l-long subsequences. In the standard approach, the length of a uniformly random sequence that can be unambiguously reconstructed is limited to n = O(2(l)) due to repetitive subsequences causing reconstruction degeneracies. We present a modified sequencing method that overcomes this limitation without the need for different types of biochemical assays and is robust to error.

Microfluidic technology has revolutionized the control of flows at small scales giving rise to new possibilities for assembling complex structures on the microscale. We analyze different possible algorithms for assembling arbitrary structures, and demonstrate that a sequential assembly algorithm can manufacture arbitrary 3D structures from identical constituents. We illustrate the algorithm by showing that a modified Hele-Shaw cell with 7 controlled flow rates can be designed to construct the entire English alphabet from particles that irreversibly stick to each other.

The results of an experimental investigation into the threshold boundary between laminar and disordered pipe flow are presented. Complex features have been uncovered using a highly refined experimental approach where an intermediate periodic state forms an integral part of the transition sequence. In accord with the suggestions produced by a numerical investigation, the boundary is found to be folded with a complicated structure. This raises important questions about accepted definitions of threshold amplitudes in this long-standing problem.

Flows through pipes and channels are the most common means to transport fluids in practical applications and equally occur in numerous natural systems. In general, the transfer of fluids is energetically far more efficient if the motion is smooth and laminar because the friction losses are lower. However, even at moderate velocities pipe and channel flows are sensitive to minute disturbances, and in practice most flows are turbulent. Investigating the motion and spatial distribution of vortices, we uncovered an amplification mechanism that constantly feeds energy from the mean shear into turbulent eddies. At intermediate flow rates, a simple control mechanism suffices to intercept this energy transfer by reducing inflection points in the velocity profile. When activated, an immediate collapse of turbulence is observed, and the flow relaminarizes.

We demonstrate the existence of a large number of exact solutions of plane Couette flow, which share the topology of known periodic solutions but are localized in one spatial dimension. Solutions of different size are organized in a snakes-and-ladders structure strikingly similar to that observed for simpler pattern-forming partial differential equations. These new solutions are a step towards extending the dynamical systems view of transitional turbulence to spatially extended flows.

Plane Couette flow, the flow between two parallel plates moving in opposite directions, belongs to the group of shear flows where turbulence occurs while the laminar profile is stable. Experimental and numerical studies show that at intermediate Reynolds numbers turbulence is transient and that the lifetimes are distributed exponentially. However, these studies have remained inconclusive about a divergence in lifetimes above a critical Reynolds number. The extensive numerical results for flow in a box of width 2pi and length 8pi presented here cover observation times up to 12,000 units and show that while the lifetimes increase rapidly with Reynolds number, they do not indicate a divergence and therefore no transition to persistent turbulence.

Direct numerical simulation of transitional pipe flow is carried out in a long computational domain in order to characterize the dynamics within the saddle region of phase space that separates laminar flow from turbulent intermittency. For Reynolds numbers ranging from Re=1800 to 2800, a shoot and bisection method is used to compute critical trajectories. The chaotic saddle or edge state approached by these trajectories is studied in detail. For Re< or =2000 the edge state and the corresponding intermittent puff are shown to share similar averaged global properties. For Re> or =2200, the puff length grows unboundedly whereas the edge state varies only little with Re. In this regime, transition is shown to proceed in two steps: first the energy grows to produce a localized turbulent patch, which then, during the second stage, spreads out to fill the pipe.