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Micro-CT imaging and pore-scale modelling have developed rapidly over the last decade by bridging the disciplines of geology, reservoir engineering, image processing, and computational fluid dynamics. They have provided new pathways for understating complex transport phenomena in heterogeneous geological formations. However, direct simulation of flow in these complex three-dimensional geometries can be difficult and time-consuming. Machine learning and Convolutional Neural Networks (CNN), as a part of the broader field of Artificial Intelligence (AI), can be integrated into the framework of pore-scale modelling. We propose a neural network architecture that considers features of the rock geometry as well as the conservation of mass and predicts the velocity distribution on the images. The method can be applied to two or three-dimensional rock images. The reliability of the flow prediction is studied by comparing the predicted permeability versus ground truth values as a bulk measure. Then, we study the accuracy of solute transport modelling. The results show that velocity fields obtained by CNN can have a considerable degree of error and are not suitable for accurate transport simulations. Finally, challenges and opportunities for the development of machine-learning approaches in porous media applications will be discussed.

Somatic activating mutations of PIK3CA are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of PIK3CA -driven VMs consisting of human umbilical vein endothelial cells expressing PIK3CA activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models. Pathologic morphologies occurred concomitant with up-regulation of Rac1/p21-activated kinase (PAK), mitogen-activated protein kinase cascades (MEK/ERK), and mammalian target of rapamycin (mTORC1/2) signaling networks. We observed differential effects between alpelisib, a PIK3CA inhibitor, and rapamycin, an mTORC1 inhibitor, in mitigating matrix degradation and network topology. While both were effective in preventing vessel enlargement, rapamycin failed to reduce MEK/ERK and mTORC2 activity and resulted in hyperbranching, while inhibiting PAK, MEK1/2, and mTORC1/2 mitigates abnormal growth and vascular dilation. Collectively, these findings demonstrate an in vitro platform for VMs and establish a role of dysregulated Rac1/PAK and mTORC1/2 signaling in PIK3CA -driven VMs.

Soft Systems Methodology (SSM) holds promise as an effective approach to addressing real-world problem situations. However, new learners of SSM can expect a number of challenges in learning the approach: its ambiguity and complexity, the number of likely unfamiliar concepts, its focus on rational analysis over emotion, and the demanding environment in which it is applied. This paper furthers the discussion of the teaching and learning of SSM in undergraduate education by considering SSM and its components from a skills-based perspective. We suggest that attention to critical, underlying component behaviors that make up SSM and an increased consideration of emotional issues in its application are key to improving learning outcomes for initial learners. We explore challenges and an approach for address these through an illustrative case involving an undergraduate dissertation project. Finally, we offer a number of recommendations and possible future lines of research which could support SSM’s more widespread adoption in education and practice.

Somatic activating mutations of PIK3CA are associated with the development of vascular malformations (VMs). Here, we describe a microfluidic model of PIK3CA-driven VMs consisting of human umbilical vein endothelial cells (HUVECs) expressing PIK3CA activating mutations embedded in 3D hydrogels. We observed enlarged and irregular vessel phenotypes, consistent with clinical signatures and concomitant with PI3K-driven upregulation of Rac1/PAK, MEK/ERK, and mTORC1/2 signaling. We observed differential effects between Alpelisib, a PIK3CA inhibitor, and Rapamycin, an mTORC1 inhibitor, in mitigating matrix degradation and vascular network topology. While both drugs are effective in preventing vessel enlargement, Alpelisib suppressed mTORC2-dependent AKT1 phosphorylation and MEK/ERK signaling. Rapamycin failed to reduce MEK/ERK and mTORC2 activity and resulted in vascular hyperbranching, while inhibiting PAK, MEK1/2, and mTORC1/2 signaling mitigates abnormal growth and vascular dilation. Collectively, these findings establish an in vitro platform for modeling VMs and confirm a role of dysregulated Rac1/PAK and mTORC1/2 signaling in PIK3CA-driven VMs.

This study represents a first time that perstraction was assessed as a process to remove perfluorooctanoic acid (PFOA) from water. In the perstraction process, PFOA permeates through a membrane from water to a solvent. The membrane used in this study was polydimethylsiloxane (PDMS). The experimental approach included the following: (1) measurement of partition coefficients for PFOA between water and selected solvents; (2) determination of solubility and diffusivity of the solvents in PDMS; (3) determination of the uptake of PFOA in PDMS; (4) determination of the effects of selected particles imbedded in the PDMS on PFOA uptake and solvent absorption; and (5) demonstration of the perstraction process to remove PFOA from water. PFOA preferentially partitioned to alcohols over water. In addition, ZnO and CuO particles in PDMS significantly enhanced the rate at which PFOA was absorbed in PDMS from deionized water due to ionic interactions. The perstraction of PFOA from deionized water into hexanol was demonstrated. However, perstraction was not successful at removing PFOA from tap water. While the application of perstraction to removing PFOA from water is limited, the idea was demonstrated and information contained within this manuscript is new.

Previously reported in vitro release test methods for drug-releasing vaginal rings containing poorly water-soluble drugs have described use of water-alcohol systems or surfactant solutions in efforts to maintain sink conditions. Here, as part of efforts to more closely match in vitro and in vivo release for the 25 mg dapivirine matrix-type silicone elastomer vaginal ring for HIV prevention, we have investigated alternatives to the 1:1 v/v water/isopropanol medium described previously. Specifically, we evaluated dapivirine release from rings into (i) monophasic water/isopropanol mixtures of varying compositions and (ii) biphasic buffer/octanol systems using pH 4.2 and pH 7.0 buffers. The rate and mechanism of dapivirine release were dependent upon the isopropanol concentration in the release medium, in accordance with the observed trend in drug solubility. At 0 and 10% v/v isopropanol concentrations, dapivirine release followed a partition-controlled mechansim. For media containing ≥ 20% v/v isopropanol, in vitro release of dapivirine was significantly increased and obeyed permeation-controlled kinetics. Cumulative release of ~3.5 mg dapivirine over 28 days was obtained using a water isopropanol mixture containing 20% v/v isopropanol, similar to the ~4 mg dapivirine released in vivo. Dapivirine release into the biphasic buffer/octanol system (intended to mimic the fluid/tissue environment in vivo) was constrained by the limited solubility of dapivirine in the buffer component in which the ring resided, such that cumulative dapivirine release was consistently lower than that observed with the 20% v/v isopropanol in water medium. Release into the biphasic system was also pH dependent, in line with dapivirine’s pKaand with potential implications for in vivo release and absorption in women with elevated vaginal pH.Graphical abstract

Relative permeability is commonly used to model immiscible fluid flow through porous materials. In this work, we derive the relative permeability relationship from conservation of energy, assuming that the system to be non-ergodic at large length scales and relying on averaging in both space and time to homogenize the behavior. Explicit criteria are obtained to define stationary conditions: (1) there can be no net change for extensive measures of the system state over the time averaging interval; (2) the net energy inputs into the system are zero, meaning that the net rate of work done on the system must balance with the heat removed; and (3) there is no net work performed due to the contribution of internal energy fluctuations. Results are then evaluated based on direct numerical simulation. Dynamic connectivity is observed during steady-state flow, which is quantitatively assessed based the Euler characteristic. We show that even during steady-state flow at low capillary number ([Formula: see text]), typical flow processes will explore multiple connectivity states. The residence time for each connectivity state is captured based on the time-and-space average. The distribution for energy fluctuations is shown to be multi-modal and non-Gaussian when terms are considered independently. However, we demonstrate that their sum is zero. Given an appropriate choice of the thermodynamic driving force, we show that the conventional relative permeability relationship is sufficient to model the energy dissipation in systems with complex pore-scale dynamics that routinely alter the structure of fluid connected pathways.

PurposeThe strategy map represents a major contribution to the theory and practice of performance management. However, it has failed to realize its full potential due to a lack of theoretical and conceptual development. Therefore, the purpose of this paper is to revisit the theories of strategy maps to better understand how and in what circumstances they benefit performance management.Design/methodology/approachThe study employs realist synthesis, a method of systematic literature review. A theory on how strategy maps work is extracted from performance management literature, which are subsequently evaluated through a critical examination of empirical studies.FindingsA theory of how strategy maps are meant work is presented in relation to the generic performance management stages of problem structuring, development and use, where they can serve as a tool for discovery and by stimulating social interactions. Based on the findings, 12 propositions are offered related to the effective use of strategy maps within a performance management framework.Research limitations/implicationsThe introduction of the strategy map to performance management represented a breakthrough in how organizational performance could be understood and communicated. This study goes a step further by considering how they work and in what circumstances. In so doing, the study aims to open the way for new and more effective applications of strategy maps within the changing performance management context.Practical implicationsThis study provides practitioners with actionable propositions which can help in effectively using strategy maps.Originality/valueDistinguishing the aims and mechanisms of the strategy map along performance management systems has the potential to greatly increase their effectiveness in practice as a powerful, but underutilized tool. This paper also demonstrates how realist synthesis, currently an uncommon method in management studies, facilitated the creation of a new perspective of strategy maps to fit specifically within performance management.

Complexity, paradox, tension, and contradiction are increasingly seen as permeating all aspects of organizational life. Yet despite ongoing advancement, both our understanding of the nature of complexity and how to use this increased appreciation of it in practice are still developing. In this spirit, this article considers organizational agility and how to achieve it. Here, current discussions of organizational agility have failed to sufficiently address the fundamental tensions inherent in learning stemming from conflicting goals and incentives, evident in an ongoing discussion of theory-informed approaches for bringing about organizational agility. In this article, we claim that incorporating a dialectical perspective of learning would provide a means of understanding the successes and failures of practices aimed at bringing about agility. We consider the maligned dialectic, four fallacious ways of thinking that hinder agility, and the extent to which these can be overcome. As evidence, we present a case of Agile implementation in which one of the authors acted as a consultant and involving a large-scale social change. Considering this from a dialectical perspective, we discuss ways that dysfunction in achieving agility might be reduced through disruptive interventions, such as Agile.

This paper explores the implications of adopting a critical realist approach to soft systems methodology (SSM) both to address local problematic situations and to develop deeper explanations. However, its potential as a means for developing generalizable knowledge for management science has been limited due at least in part to its adherence to strong interpretivism. After exploring the history of soft systems methodology and basic tenants of critical realism, the paper builds on previous discussions of ways in which SSM is compatible with a critical realist approach. Next, the consequences for such an approach are considered by examining a case in which SSM was integrated into a critical realist approach for discovery as means to guide large-scale reform in a non-profit organization. The case revealed that critical realism served as an effective guide both for incorporating existing knowledge as well as setting the stage for its possible modification. Opportunities and challenges in the approach are presented. Apart from the adoption of a realist ontology, a critical realist approach to SSM requires assuming a dual-role as an insider--outsider, which presents a number of challenges. However, it appears soft systems methodology are highly compatible and could serve to help bridge the practice--research gap.

Decellularized adipose tissue (DAT) has shown potential as a regenerative scaffold for plastic and reconstructive surgery to augment or replace damaged or missing adipose tissue (e.g. following lumpectomy or mastectomy). The mechanical properties of soft tissue substitutes are of paramount importance in restoring the natural shape and appearance of the affected tissues, and mechanical mismatching can lead to unpredictable scar tissue formation and poor implant integration. The goal of this work was to assess the linear elastic and hyperelastic properties of decellularized human adipose tissue and compare them to those of normal breast adipose tissue. To assess the influence of the adipose depot source on the mechanical properties of the resultant decellularized scaffolds, we performed indentation tests on DAT samples sourced from adipose tissue isolated from the breast, subcutaneous abdominal region, omentum, pericardial depot and thymic remnant, and their corresponding force–displacement data were acquired. Elastic and hyperelastic parameters were estimated using inverse finite element algorithms. Subsequently, a simulation was conducted in which the estimated hyperelastic parameters were tested in a real human breast model under gravity loading in order to assess the suitability of the scaffolds for implantation. Results of these tests showed that in the human breast, the DAT would show similar deformability to that of native normal tissue. Using the measured hyperelastic parameters, we were able to assess whether DAT derived from different depots exhibited different intrinsic nonlinearities. Results showed that DAT sourced from varying regions of the body exhibited little intrinsic nonlinearity, with no statistically significant differences between the groups.

As one of the most commonly performed neurosurgical procedures, ventriculostomy training simulators are becoming increasingly familiar features in research institutes and teaching facilities. Despite their widespread implementations and adoption, simulators to date have not fully explored the landscape of performance metrics that reflect surgical proficiency. They opt instead for measures that are qualitative or simple to compute and conceptualize. In this paper, we examine and compare the use of various metrics to characterize the performance of users on simulated part-task ventriculostomy scenarios derived from patient data. As an initial study, we examine how our metrics relate to expert classification of scenario difficulty as well as measures of anatomical variation.

Numerous augmented reality image guidance tools have been evaluated under specific clinical criteria, but there is a lack of investigation into the broad effect on targeting ability and perception. In this paper, we evaluated performance of 18 subjects on a targeting task modeling ventriculostomy trajectory planning. Users targeted ellipsoids within a mannequin head using both an augmented reality interface and a traditional slice-based interface for planning. Users were significantly more accurate by several measures using augmented reality guidance, but were seen to have significant targeting bias; depth was underestimated by users with low targeting success. Our results further demonstrate the need for superior depth cues in augmented reality implementations while providing a framework for objective evaluation of augmented reality interfaces.

The placement of an external ventricular drain is one of the most commonly performed neurosurgical procedures, and consequently, is an essential skill to be mastered by neurosurgical trainees. The optimal placement of the drain involves choosing an appropriate burr hole on the skull and blindly placing a catheter through the burr hole to intersect a lateral ventricle in order to drain cerebrospinal fluid and relieve intracranial pressure. Undesirable trajectories lead to multiple tries in order to hit the ventricle, with potential risk of damaging eloquent brain areas. In this paper, we describe the development of a simulation environment to train residents on the acquisition of these targeting skills before attempting the placement on live patients. The platform is coupled with an augmented reality image-guidance tool, developed in our lab, to help with the visualization of the ventricles in the patient's head. Performance is evaluated using Fitts' methodology (Fitts, 1954), which respects the users ability to trade-off speed and accuracy.

Cosmological simulations follow the formation of nonlinear structure in dark and luminous matter. The associated simulation volumes and dynamic range are very large, making visualization both a necessary and challenging aspect of the analysis of these datasets. Our goal is to understand sources of inconsistency between different simulation codes that are started from the same initial conditions. Quantitative visualization supports the definition and reasoning about analytically defined features of interest. Comparative visualization supports the ability to visually study, side by side, multiple related visualizations of these simulations. For instance, a scientist can visually distinguish that there are fewer halos (localized lumps of tracer particles) in low-density regions for one simulation code out of a collection. This qualitative result will enable the scientist to develop a hypothesis, such as loss of halos in low-density regions due to limited resolution, to explain the inconsistency between the different simulations. Quantitative support then allows one to confirm or reject the hypothesis. If the hypothesis is rejected, this step may lead to new insights and a new hypothesis, not available from the purely qualitative analysis. We will present methods to significantly improve the Scientific analysis process by incorporating quantitative analysis as the driver for visualization. Aspects of this work are included as part of two visualization tools, ParaView, an open-source large data visualization tool, and Scout, an analysis-language based, hardware-accelerated visualization tool.

Graphically realistic, haptics-enabled, virtual reality surgical simulations are becoming increasingly popular training tools for neurosurgical procedures and surgical skills. Compared with traditional training models, virtual simulations are safe, versatile, consistent, and are relatively cost effective. Most simulations are deficient, however, in representing the diverse anatomical variations that occur clinically. In this work, we describe the design and implementation of a pipeline to create patient-specific surgical scenarios for simulator-based training of the endoscopic third ventriculostomy: the procedure of choice for treating obstructive hydrocephalus.

Image guidance can provide surgeons with valuable contextual information during a medical intervention. Often, image guidance systems require considerable infrastructure, setup-time, and operator experience to be utilized. Certain procedures performed at bedside are susceptible to navigational errors that can lead to complications. We present an application for mobile devices that can provide image guidance using augmented reality to assist in performing neurosurgical tasks. A methodology is outlined that evaluates this mode of visualization from the standpoint of perceptual localization, depth estimation, and pointing performance, in scenarios derived from a neurosurgical targeting task. By measuring user variability and speed we can report objective metrics of performance for our augmented reality guidance system.

Purpose To report the results of early enteral feeding in patients with cancer after outpatient placement of a percutaneous fluoroscopy-guided gastrostomy (PFG). Materials and Methods From January 2008 through December 2008, 121 consecutive patients with cancer underwent outpatient placement of a PFG for nutrition. Of these patients, 118 patients met criteria for early feeding, and 113 were successfully fed early (after at least 3 hours). Of the patients fed early, 5 had insufficient follow-up for further analysis leaving 108 patients for outcomes analysis. After placement of the PFG, patients were put on low-wall suction via the PFG for 1 hour followed by feeding via the PFG at least 3 hours after placement. Follow-up evaluation was done the next business day. The medical records were reviewed for 30-day outcomes of early feeding, technical aspects of the procedures, and complications. Results After placement of the PFG, 98% (118 of 121) of patients met criteria for early feeding, and 93% (113 of 121) of patients were successfully fed early. The median time between the end of the procedure and initiation of feeding was 4 hours (interquartile range, 3.7–4.4 h). The 30-day minor complication rate was 14% (15 of 108), and the 30-day major complication rate was 1% (1 of 108). No complications were directly attributable to early feeding. Conclusions Early initiation of tube feedings after outpatient placement of a PFG was well tolerated in patients with cancer and carried comparable risks to previously reported results using traditional delayed feeding protocols. Early feeding provided patients with prompt enteral nutrition and eliminated the need for routine hospital admission after the procedure.

Neuroanatomy is one of the most challenging sections of anatomy to learn, partially related to the intricate relation of multiple 3D structures. As part of the medical student curriculum, it is usually taught in 2D using illustrations and plastinated brain section, since the number of hours devoted to anatomy have dropped in the curriculum, making the dissection of brain too time-consuming to be done. In this study we are analyzing the role of innate spatial ability of novices in learning some basic structures and placing them back in a 3D volumetric brain. Two tasks are performed after a short training session: the first one is to localize the ventricular tip as would be required during a temporal lobectomy, and the second task requires that the subject 'reconstruct' 3D anatomical structures within the context of our 3D brain model. We report our findings on the performance scores obtained from a population of subjects of differing backgrounds and spatial abilities.

This paper describes the design and development of a software tool for the evaluation and training of surgical residents using an interactive, immersive, virtual environment. Our objective was to develop a tool to evaluate user spatial reasoning skills and knowledge in a neuroanatomical context, as well as to augment their performance through interactivity. In the visualization, manually segmented anatomical surface images of MRI scans of the brain were rendered using a stereo display to improve depth cues. A magnetically tracked wand was used as a 3D input device for localization tasks within the brain. The movement of the wand was made to correspond to movement of a spherical cursor within the rendered scene, providing a reference for localization. Users can be tested on their ability to localize structures within the 3D scene, and their ability to place anatomical features at the appropriate locations within the rendering.

MobiVis is a visual analytics tools to aid in the process of processing and understanding complex relational data, such as social networks. At the core of these tools is the ability to filter complex networks structurally and semantically, which helps us discover clusters and patterns in the organization of social networks. Semantic filtering is obtained via an ontology graph, based on another visual analytics tool, called OntoVis. In this summary, we describe how these tools where used to analyze one of the mini-challenges of the 2008 VAST challenge.

Current and upcoming cosmological observations allow us to probe structures on smaller and smaller scales, entering highly nonlinear regimes. In order to obtain theoretical predictions in these regimes, large cosmological simulations have to be carried out. The promised high accuracy from observations make the simulation task very demanding: the simulations have to be at least as accurate as the observations. This requirement can only be fulfilled by carrying out an extensive code validation program. The first step of such a program is the comparison of different cosmology codes including gravitation interactions only. In this paper we extend a recently carried out code comparison project to include five more simulation codes. We restrict our analysis to a small cosmological volume which allows us to investigate properties of halos. For the matter power spectrum and the mass function, the previous results hold, with the codes agreeing at the 10% level over wide dynamic ranges. We extend our analysis to the comparison of halo profiles and investigate the halo count as a function of local density. We introduce and discuss ParaView as a flexible analysis tool for cosmological simulations, the use of which immensely simplifies the code comparison task., Comment: 28 pages, 14 figures

Acquisition and fusion of multiple imaging modalities is becoming an increasingly desired clinical practice. This is particularly the case in radiation therapy, where dosage must be determined using electron density calculations from CT images, which lack the contrast to resolve soft-tissue structures. This often necessitates the fusion of corresponding MRI images in order to plot radiation trajectories safely around critical tissues. Simultaneous visualization of multiple volumes using direct volume rendering (DVR) techniques offers a number of advantages over traditional visualization methods. Specifically, fused visualization enhances the relational aspects of volumes, providing improved context [cite the first one]. However, there are many challenges involved in implementing DVR using fused data sets. The primary challenge is determining how images overlap to provide meaningful information. Additionally, there is increased computational complexity beyond standard DVR techniques, threatening real-time applications of fused DVR. These difficulties are evident to users of such systems as they must manage complex user interfaces and poor application performance. In this work, we introduce a user-centric multi-volume DVR technique which addresses issues of performance and ease of use. Through an intuitive interface, users are able to spatially define regions of interest, determining the relative contributions of each modality in the output rendering.