Search

A survey has been carried out in three regions of north-east Italy, Emilia Romagna, Veneto and Friuli Venezia Giulia, with four objectives: (a) to update the statistics on the use of pipe drainage; (b) to describe the farms that adopt this technique as a replacement of the traditional surface drainage methods; (c) to characterise the featuresof the drained soils and of the drainage systems, and (d) to assess their performance. With almost 79 000 ha drained, the Regions presentalmost all of the pipe drained area in Italy. Pipe drainage first saw applications in the late seventies and became increasingly popular during the eighties. Most pipe drainage systems are installed in heavy soils, where the underground waterlogging is due to seasonal perched water table or to infiltrations from rivers or sea. Due to the pedoclimatic variability of the area, slightly different solutions in terms of design variables and installation criteria are found, but the following features are quite common: drain spacing 11--13 m, slope 0.1--0.3%, depth 0.9-- 1 m. The pipe drains discharge in open collectors(single systems). An increasing interest for the use of the drainagesystems for subirrigation purposes has been observed, particularly in Veneto, requiring some adjustment in the drainage design. The performance of drainage in terms of control of water table depth and maintenance requirements are considered satisfactory in almost all the cases. The most effective solutions for successfully managing the subirrigation are also described. The introduction of pipe drains allows toenlarge fields (to more than 10 ha) and to save time for carrying out the operations for crop cultivation. The crop yield in pipe drainedfields is slightly higher than that obtained in the traditionally drained fields, with the exception of winter wheat. [ABSTRACT FROM AUTHOR]

The transverse spin correlations Ax,x and Ay,y have been measured in the dp→pspec{pp}sp- reaction at COSY-ANKE at 353 MeV per nucleon. Here {pp}s denotes a proton-proton pair with low excitation energy, which is dominantly in the ¹S0 state. By measuring three protons in the final state it was possible to extract events where there was a spectator proton pspec so that the reaction could be interpreted in terms of quasifree n p→{pp}sp-. The proton and neutron analyzing powers in this reaction were also deduced from this data set by averaging over the polarizations of the deuteron beam and hydrogen target, respectively. The values of Ay were shown to be consistent with a refined analysis of our earlier results obtained with a polarized proton incident on a deuterium target. Taking these data in combination with our previous measurements of the differential cross sections and analyzing powers in the p p→{pp}s p° reaction, a more robust partial wave decomposition was achieved. Three different acceptable solutions were found, and the only way of resolving this ambiguity without further theoretical input would be through a measurement of the mixed spin-correlation parameter Ax,z. [ABSTRACT FROM AUTHOR]

Abstract: The PAX Collaboration has successfully performed a spin-filtering experiment with protons at the COSY-ring. The measurement allowed the determination of the spin-dependent polarizing cross section, that compares well with the theoretical prediction from the nucleon–nucleon potential. The test confirms that spin-filtering can be adopted as a method to polarize a stored beam and that the present interpretation of the mechanism in terms of the proton–proton interaction is correct. The outcome of the experiment is of utmost importance in view of the possible application of the method to polarize a beam of stored antiprotons. [Copyright &y& Elsevier]

Abstract: In order to test chiral perturbation theory and establish links between p-wave pion production in nucleon–nucleon collisions and low energy three-nucleon scattering, an extensive programme of experiments on pion production is currently underway at COSY-ANKE. The final proton pair is measured at very low excitation energy, leading to an S-wave diproton, denoted here as . By using a deuterium target we have obtained data on the differential cross section and analysing power of the quasi-free reaction at 353 MeV. The spectator proton was either measured directly in silicon tracking telescopes or reconstructed using the momentum of a detected . Both observables can be described in terms of s-, p-, and d-wave pion production amplitudes. Taken together with the analogous data on the reaction, full partial wave decompositions of both processes were carried out. [Copyright &y& Elsevier]

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG)., Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma. The following models were given the base parameters in addition to one of the following biomarkers: structural features (optic nerve parameters, retinal nerve fiber layer [RNFL], ganglion cell complex [GCC] and macular thickness), choroidal thickness, and RNFL and GCC thickness only, by optical coherence tomography (OCT); and vascular features by OCT angiography (OCTA)., Results: MLPs of three different structures were evaluated with tenfold cross validation. The testing area under the receiver operating characteristic curve (AUC) of the models were compared with independent samples t-tests. The vascular and structural models both had significantly higher accuracies than the base model, with the hemodynamic AUC (0.819) insignificantly outperforming the structural set AUC (0.816). The GCC + RNFL model and the model containing all structural and vascular features were also significantly more accurate than the base model., Conclusions: Neural network models indicate that OCTA optic nerve head vascular biomarkers are equally useful for ML diagnosis of POAG when compared to OCT structural biomarker features alone.

Spontaneous filling and voiding cycles represent a key dynamical feature of the healthy lower urinary tract. Some urinary tract dysfunctions, such as over-flow incontinence, may alter the natural occurrence of these cycles. As the function of the lower urinary tract arises from the interplay of a multitude of factors, it is difficult to determine which of them can be modulated to regain spontaneous cycles. In this study, we develop a mathematical model of the lower urinary tract that can capture filling and voiding cycles in the form of periodic solutions of a system of ordinary differential equations. After experimental validation, we utilize this model to study the effect that several physiological quantities have on the onset of cycles. We find that some parameters have an associated numerical threshold that determines whether the system exhibits healthy cycles or settles in a state of constant overflow., (© 2024. The Author(s), under exclusive licence to the Society for Mathematical Biology.)

We present our continuous efforts from a modeling and numerical viewpoint to develop a powerful and flexible mathematical and computational framework called Ocular Mathematical Virtual Simulator (OMVS). The OMVS aims to solve problems arising in biomechanics and hemodynamics within the human eye. We discuss our contribution towards improving the reliability and reproducibility of computational studies by performing a thorough validation of the numerical predictions against experimental data. The OMVS proved capable of simulating complex multiphysics and multiscale scenarios motivated by the study of glaucoma. Furthermore, its modular design allows the continuous integration of new models and methods as the research moves forward, and supports the utilization of the OMVS as a promising non-invasive clinical investigation tool for personalized research in ophthalmology., (© 2023 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men., Competing Interests: GG would like to disclose that she received remuneration from Foresite Healthcare LLC for serving as a consultant. MS would like to disclose that she received remuneration from Foresite Healthcare LLC for serving on the advisory board. These relationships do not conflict with the work in this article and are pursuant to the University of Missouri’s policy on outside activities. The remaining 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., (© 2023 Zaid, Sala, Despins, Heise, Popescu, Skubic, Ahmad, Emter, Huxley and Guidoboni.)

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results ( i ) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, ( ii ) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and ( iii ) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

This study investigated the heterogeneity of ocular hemodynamic biomarkers in early open angle glaucoma (OAG) patients and healthy controls of African (AD) and European descent (ED). Sixty OAG patients (38 ED, 22 AD) and 65 healthy controls (47 ED, 18 AD) participated in a prospective, cross-sectional study assessing: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), visual field (VF) and vascular densities (VD) via optical coherence tomography angiography (OCTA). Comparisons between outcomes were adjusted for age, diabetes status and BP. VF, IOP, BP and OPP were not significantly different between OAG subgroups or controls. Multiple VD biomarkers were significantly lower in OAG patients of ED ( p < 0.05) while central macular VD was lower in OAG patients of AD vs. OAG patients of ED ( p = 0.024). Macular and parafoveal thickness were significantly lower in AD OAG patients compared to those of ED ( p = 0.006-0.049). OAG patients of AD had a negative correlation between IOP and VF index (r = -0.86) while ED patients had a slightly positive relationship (r = 0.26); difference between groups ( p < 0.001). Age-adjusted OCTA biomarkers exhibit significant variation in early OAG patients of AD and ED.

Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians., Competing Interests: Conflicts of Interest: Alon Harris would like to disclose that he received remuneration from AdOM, Qlaris, Luseed, and Cipla for serving as a consultant, and he serves on the board of AdOM, Qlaris, and Phileas Pharma. Alon Harris holds an ownership interest in AdOM, Luseed, Oxymap, Qlaris, Phileas Pharma, SlitLed, and QuLent. Giovanna Guidoboni would like to disclose that she received remuneration from Foresite Healthcare and Qlaris for serving as a consultant.

Aims: Understand what progress has been made toward a functionally predictive lower urinary tract (LUT) model, identify knowledge gaps, and develop from them a path forward., Methods: We surveyed prominent mathematical models of the basic LUT components (bladder, urethra, and their neural control) and categorized the common modeling strategies and theoretical assumptions associated with each component. Given that LUT function emerges from the interaction of these components, we emphasized attempts to model their connections, and highlighted unmodeled aspects of LUT function., Results: There is currently no satisfactory model of the LUT in its entirety that can predict its function in response to disease, treatment, or other perturbations. In particular, there is a lack of physiologically based mathematical descriptions of the neural control of the LUT., Conclusions: Based on our survey of the work to date, a potential path to a predictive LUT model is a modular effort in which models are initially built of individual tissue-level components using methods that are extensible and interoperable, allowing them to be connected and tested in a common framework. A modular approach will allow the larger goal of a comprehensive LUT model to be in sight while keeping individual efforts manageable, ensure new models can straightforwardly build on prior research, respect potential interactions between components, and incentivize efforts to model absent components. Using a modular framework and developing models based on physiological principles, to create a functionally predictive model is a challenge that the field is ready to undertake., (© 2022 Wiley Periodicals LLC.)

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced ( pe- ) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase ( p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery ( p < 0.001) and retinal venules ( p = 0.003) and a non-significant increase in the resistance in the central retinal vein ( p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system. This work aims at building a mechanistic connection between changes in the BCG signal, changes in the P-V loops and changes in cardiac function. A mechanism-driven model based on cardiovascular physiology has been used as a virtual laboratory to predict how changes in cardiac function will manifest in the BCG waveform. Specifically, model simulations indicate that a decline in LV contractility results in an increase of the relative timing between the ECG and BCG signal and a decrease in BCG amplitude. The predicted changes have subsequently been observed in measurements on three swine serving as pre-clinical models for pre- and post-myocardial infarction conditions. The reproducibility of BCG measurements has been assessed on repeated, consecutive sessions of data acquisitions on three additional swine. Overall, this study provides experimental evidence supporting the utilization of mechanism-driven mathematical modeling as a guide to interpret changes in the BCG signal on the basis of cardiovascular physiology, thereby advancing the BCG technique as an effective method for non-invasive monitoring of cardiac function., Competing Interests: GG would like to disclose that she received remuneration from Foresite Healthcare LLC for serving as a consultant. MS also discloses a conflict with Foresite Healthcare LLC outside the submitted work and patents licensed to Foresite Healthcare LLC. PR-L holds equity in REGENCOR. MK holds equity in Anchored RSK3 Inhibitors, LLC, and Cardiac RSK3 Inhibitors, LLC. These relationships are pursuant to University of Missouri's policy on outside activities. The remaining 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 © 2022 Zaid, Sala, Ivey, Tharp, Mueller, Thorne, Kelly, Silva, Amin, Ruiz-Lozano, Kapiloff, Despins, Popescu, Keller, Skubic, Ahmad, Emter and Guidoboni.)

Purpose: This study proposes a novel approach to obtain personalized estimates of cardiovascular parameters by combining (i) electrocardiography and ballistocardiography for noninvasive cardiovascular monitoring, (ii) a physiology-based mathematical model for predicting personalized cardiovascular variables, and (iii) an evolutionary algorithm (EA) for searching optimal model parameters. Methods: Electrocardiogram (ECG), ballistocardiogram (BCG), and a total of six blood pressure measurements are recorded on three healthy subjects. The R peaks in the ECG are used to segment the BCG signal into single BCG curves for each heart beat. The time distance between R peaks is used as an input for a validated physiology-based mathematical model that predicts distributions of pressures and volumes in the cardiovascular system, along with the associated BCG curve. An EA is designed to search the generation of parameter values of the cardiovascular model that optimizes the match between model-predicted and experimentally-measured BCG curves. The physiological relevance of the optimal EA solution is evaluated a posteriori by comparing the model-predicted blood pressure with a cuff placed on the arm of the subjects to measure the blood pressure. Results: The proposed approach successfully captures amplitudes and timings of the most prominent peak and valley in the BCG curve, also known as the J peak and K valley. The values of cardiovascular parameters pertaining to ventricular function can be estimated by the EA in a consistent manner when the search is performed over five different BCG curves corresponding to five different heart-beats of the same subject. Notably, the blood pressure predicted by the physiology-based model with the personalized parameter values provided by the EA search exhibits a very good agreement with the cuff-based blood pressure measurement. Conclusion: The combination of EA with physiology-based modeling proved capable of providing personalized estimates of cardiovascular parameters and physiological variables of great interest, such as blood pressure. This novel approach opens the possibility for developing quantitative devices for noninvasive cardiovascular monitoring based on BCG sensing., Competing Interests: GG would like to disclose that she received remuneration from Foresite Healthcare LLC for serving as a consultant. MS also discloses a conflict with Foresite Healthcare LLC outside the submitted work and patents licensed to Foresite Healthcare LLC. These relationships are pursuant to the University of Missouri's policy on outside activities. The remaining 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 © 2022 Marazzi, Guidoboni, Zaid, Sala, Ahmad, Despins, Popescu, Skubic and Keller.)

Modeling biological dynamical systems is challenging due to the interdependence of different system components, some of which are not fully understood. To fill existing gaps in our ability to mechanistically model physiological systems, we propose to combine neural networks with physics-based models. Specifically, we demonstrate how we can approximate missing ordinary differential equations (ODEs) coupled with known ODEs using Bayesian filtering techniques to train the model parameters and simultaneously estimate dynamic state variables. As a study case we leverage a well-understood model for blood circulation in the human retina and replace one of its core ODEs with a neural network approximation, representing the case where we have incomplete knowledge of the physiological state dynamics. Results demonstrate that state dynamics corresponding to the missing ODEs can be approximated well using a neural network trained using a recursive Bayesian filtering approach in a fashion coupled with the known state dynamic differential equations. This demonstrates that dynamics and impact of missing state variables can be captured through joint state estimation and model parameter estimation within a recursive Bayesian state estimation (RBSE) framework. Results also indicate that this RBSE approach to training the NN parameters yields better outcomes (measurement/state estimation accuracy) than training the neural network with backpropagation through time in the same setting.

The time interval between the peaks in the electroccardiogram (ECG) and ballistocardiogram (BCG) waveforms, TEB, has been associated with the pre-ejection period (PEP), which is an important marker of ventricular contractility. However, the applicability of BCG-related markers in clinical practice is limited by the difficulty to obtain a replicable and consistent signal on patients. In this study, we test the feasibility of BCG measurements within a complex clinical setting, by means of an accelerometer under the head pillow of patients admitted to the Surgical Intensive Care Unit (SICU). The proposed technique proved capable of capturing TEB based on the R peaks in the ECG and the BCG in its head-to-toe and dorso- ventral directions. TEB detection was found to be consistent and repeatable both in healthy individuals and SICU patients over multiple data acquisition sessions. This work provides a promising starting point to investigate how TEB changes may relate to the patients' complex health conditions and give additional clinical insight into their care needs.

Key Points: Microvascular network architecture defines coupling of fluid and protein exchange. Network arrangements markedly reduce capillary hydrostatic pressures and resting fluid movement at the same time as increasing the capacity for change The presence of vascular remodelling or angiogenesis puts constraints of network behaviour The sites of fluid and protein exchange can be segregated to different portions of the network Although there is a net filtration of fluid from a network of exchange vessels, there are specific areas where fluid moves into the circulation (reabsorption) and, when protein is moving into tissue, the amount is insufficient under basal conditions to result in changes in oncotic pressure., Abstract: Integration of functional results obtained across scales, from chemical signalling to the whole organism, is a daunting task requiring the marriage of experimental data with mathematical modelling. In the present study, a novel coupled computational fluid dynamics model is developed incorporating fluid and protein transport using measurements in an in vivo frog (Rana pipiens) mesenteric microvascular network. The influences of network architecture and exchange are explored systematically under the common assumptions of structurally and functionally identical microvessels (Homogeneous Scenario) or microvessels classified by position in flow (Class Uniform Scenario), which are compared with realistic microvascular network components (Heterogeneous Scenario). The model incorporates ten quantities that vary within a microvessel; pressure boundary conditions are calibrated against experimental measurements. The Homogeneous Scenario standard model showed that assuming a single 'typical' capillary hides the influence of vessels arranged into a network architecture, where capillary hydrostatic pressures (p T ) are reduced, resulting in both a nonuniform distribution of blood flow and reduced volume flow rate (J f , T ). In the Class Uniform Scenario p T was further attenuated to produce a ∼60% reduction in J f , T . Finally, the Heterogeneous Scenario, incorporating measures of individual vessel surface area, demonstrates additional lowering of p T from inlet values favouring a >70% reduction of J f , T in the face of a ∼120% increase in protein movement into the tissues relative to the Homogeneous Scenario. Beyond the impacts of network architecture, an unanticipated finding was the influence of a blind-end microvessel on model convergence, indicating a profound influence of the largely unexplored dynamics of vascular remodelling on tissue perfusion., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption. The vitreous and the choroid are located at the macula boundary and provide oxygen via boundary conditions of Dirichlet type. The three capillary plexi (superficial, intermediate, and deep) of the retinal circulation pierce the macular layers and provide oxygen via a volumetric source that depends on the retinal blood flow. Oxygen profiles through the macular tissue are calculated by simulating the balance among oxygen supply, consumption and diffusion in: (a) physiological baseline conditions; (b) retinal blood flow reduced by 10%, 30% and 50% with respect to baseline; (c) choroidal oxygen level diminished by 10%, 30% and 50% with respect to baseline. Model simulations predict that: (1) the oxygenation of the foveal avascular zone is not affected by reduction in retinal blood flow; (2) a reduction in choroidal oxygen supply significantly affects the outer layers, especially the photoreceptors and outer nuclear layers; (3) the impact of reduction in choroidal oxygen supply is larger in the region more proximal to the macular center; (4) the impact of reduction in retinal blood flow is larger in the region more proximal to the macular periphery. The proposed mathematical model suggests that changes in retinal and choroidal oxygen supplies impact the oxygenation of the macular tissue differentially. These results may help better understand the pathogenesis of macular degeneration., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest. Professor A. Harris would like to disclose that he received remuneration from AdOM, Qlaris, Luseed, and Cipla for serving as a consultant, and he serves on the board of AdOM, Qlaris, and Phileas Pharma. Professor A. Harris holds an ownership interest in AdOM, Luseed, Oxymap, Qlaris, Phileas Pharma, and QuLent. All relationships listed above are pursuant to Icahn School of Medicine’s policy on outside activities. Dr. G. Guidoboni would like to disclose that she received remuneration from Foresite Healthcare LLC for serving as a consultant. Dr. G. Guidoboni holds an ownership interest in Gspace LLC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glaucoma is a multifactorial progressive and degenerative optic neuropathy representing one of the world's leading cause of irreversible blindness. Currently, reduction of intraocular pressure remains the only universally approved therapy, yet a wealth of studies has identified significant vascular contributions to the disease process in certain individuals. Population-based studies have identified important racial disparities and differential risk factors in glaucoma prevalence, incidence, and progression. A more significant vascular component has been identified in persons of African descent. Elucidating risk modifiers, including genetic and racial influence, is important when considering individually tailored clinical management of glaucoma. The application of artificial intelligence and mathematical modeling inclusive of demographic considerations, vascular health, and clinical biomarkers may help reduce disease disparities, advance personalized medicine, and provide a comprehensive model of glaucoma.

Neurodegenerative disorders (NDD) such as Alzheimer's and Parkinson's diseases are significant causes of morbidity and mortality worldwide. The pathophysiology of NDD is still debated, and there is an urgent need to understand the mechanisms behind the onset and progression of these heterogenous diseases. The eye represents a unique window to the brain that can be easily assessed via non-invasive ocular imaging. As such, ocular measurements have been recently considered as potential sources of biomarkers for the early detection and management of NDD. However, the current use of ocular biomarkers in the clinical management of NDD patients is particularly challenging. Specifically, many ocular biomarkers are influenced by local and systemic factors that exhibit significant variation among individuals. In addition, there is a lack of methodology available for interpreting the outcomes of ocular examinations in NDD. Recently, mathematical modeling has emerged as an important tool capable of shedding light on the pathophysiology of multifactorial diseases and enhancing analysis and interpretation of clinical results. In this article, we review and discuss the clinical evidence of the relationship between NDD in the brain and in the eye and explore the potential use of mathematical modeling to facilitate NDD diagnosis and management based upon ocular biomarkers., (Copyright © 2020 Guidoboni, Sacco, Szopos, Sala, Verticchio Vercellin, Siesky and Harris.)

Presents a missing funding acknowledgment for Dr. Mihail Popescu in the above named paper.

In biomedical imaging using video microscopy, understanding large tissue structures at cellular and finer resolution poses many image acquisition challenges including limited field-of-view and tissue dynamics during imaging. Automated mosaicing or stitching of live tissue video microscopy enables the visualization and analysis of subtle morphological structures and large scale vessel network architecture in tissues like the mesentery. But mosacing can be challenging if there are deformable, motion-blurred, textureless, feature-poor frames. Feature-based methods perform poorly in such cases for the lack of distinctive keypoints. Standard single block correlation matching strategies might not provide robust registration due to deformable content. In addition, the panorama suffers if there is motion blur present in a sequence. To handle these challenges, we propose a novel algorithm, Deformable Normalized Cross Correlation (DNCC) image matching with RANSAC to establish robust registration. Besides, to produce seamless panorama from motion-blurred frames we present gradient blending method based on image edge information. The DNCC algorithm is applied on Frog Mesentery sequences. Our result is compared with PSS/AutoStitch [1, 2] to establish the efficiency and robustness of the proposed DNCC method.

Introduction: To identify novel velocity waveform parameters of the ophthalmic artery and central retinal artery by computer-aided image processing of Doppler ultrasonography measurements, and to evaluate correlations between the waveform parameters and different demographics and disease severity of open-angle glaucoma patients., Methods: Thirty-six images of 36 open-angle glaucoma patients were considered. A semiautomated image processing code was used to detect the digitalized ophthalmic artery and central retinal artery velocity waveforms and to extract the waveform parameters. Concordance correlation coefficient, two-sample t-test, and Pearson's correlation coefficient were used to test for similarities, differences, and associations among variables., Results: Female glaucoma patients showed a statistically higher ophthalmic artery normalized distance between ascending and descending limb (p = 0.004), hypertensive glaucoma patients a statistically higher ophthalmic artery peak systolic velocity time (p = 0.025), glaucoma patients with hyperlipidemia a statistically higher ophthalmic artery resistivity index (p = 0.023) and a statistically higher ophthalmic artery peak systolic velocity acceleration (p = 0.025), glaucoma patients with cardiovascular diseases a statistically lower central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.033) and a statistically higher central retinal artery period (p = 0.028), and patients with different body mass index a statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p = 0.016). Groups with different disease severity, classified following the Brusini glaucoma staging system 2, showed statistically different central retinal artery normalized distance between ascending and descending limb of the wave (p < 0.001) and central retinal artery period (p = 0.016). No statistical differences were found in regard to race, diabetes status, glaucoma family history, and smoking., Discussion: Ophthalmic artery and central retinal artery computer-aided analysis of velocity waveforms could identify novel waveform parameters capable of differentiating among different demographics and disease severity of open-angle glaucoma patients.

Early detection of heart failure in older adults will be a significant issue for the foreseeable future. The current article presents a case study to describe how monitoring ballistocardiogram (BCG) waveforms captured non-invasively using sensors placed under a bed mattress can detect early heart failure changes. Heart and respiratory rates obtained from the bed sensor of a female older adult who was hospitalized with acute mixed congestive heart failure, clinic notes, and data from computer simulations reflecting increasing diastolic dysfunction were analyzed. Mean heart and respiratory rate trends obtained from her bed sensor in the prior 2 months did not indicate heart failure. BCG waveforms resulting from the simulations demonstrated changes associated with decreasing cardiac output as diastolic function worsened. Developing new methods for clinically interpreting BCG waveforms presents a significant opportunity for improving early heart failure detection. [Journal of Gerontological Nursing, 46(7), 41-46.]., (Copyright 2020, SLACK Incorporated.)

Alterations in ocular blood flow have been identified as important risk factors for the onset and progression of numerous diseases of the eye. In particular, several population-based and longitudinal-based studies have provided compelling evidence of hemodynamic biomarkers as independent risk factors for ocular disease throughout several different geographic regions. Despite this evidence, the relative contribution of blood flow to ocular physiology and pathology in synergy with other risk factors and comorbidities (e.g., age, gender, race, diabetes and hypertension) remains uncertain. There is currently no gold standard for assessing all relevant vascular beds in the eye, and the heterogeneous vascular biomarkers derived from multiple ocular imaging technologies are non-interchangeable and difficult to interpret as a whole. As a result of these disease complexities and imaging limitations, standard statistical methods often yield inconsistent results across studies and are unable to quantify or explain a patient's overall risk for ocular disease. Combining mathematical modeling with artificial intelligence holds great promise for advancing data analysis in ophthalmology and enabling individualized risk assessment from diverse, multi-input clinical and demographic biomarkers. Mechanism-driven mathematical modeling makes virtual laboratories available to investigate pathogenic mechanisms, advance diagnostic ability and improve disease management. Artificial intelligence provides a novel method for utilizing a vast amount of data from a wide range of patient types to diagnose and monitor ocular disease. This article reviews the state of the art and major unanswered questions related to ocular vascular anatomy and physiology, ocular imaging techniques, clinical findings in glaucoma and other eye diseases, and mechanistic modeling predictions, while laying a path for integrating clinical observations with mathematical models and artificial intelligence. Viable alternatives for integrated data analysis are proposed that aim to overcome the limitations of standard statistical approaches and enable individually tailored precision medicine in ophthalmology., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (i) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor-dependent, cAMP, or calcium-dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps, and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occurring at the scale of the whole eye, for which clinical assessment is feasible.