Computational Modeling of Fluid Flow and Intra-Ocular Pressure following Glaucoma Surgery

Background Glaucoma surgery is the most effective means for lowering intraocular pressure by providing a new route for fluid to exit the eye. This new pathway is through the sclera of the eye into sub-conjunctival tissue, where a fluid filled bleb typically forms under the conjunctiva. The long-term success of the procedure relies on the capacity of the sub-conjunctival tissue to absorb the excess fluid presented to it, without generating excessive scar tissue during tissue remodeling that will shut-down fluid flow. The role of inflammatory factors that promote scarring are well researched yet little is known regarding the impact of physical forces on the healing response. Methodology To help elucidate the interplay of physical factors controlling the distribution and absorption of aqueous humor in sub-conjunctival tissue, and tissue remodeling, we have developed a computational model of fluid production in the eye and removal via the trabecular/uveoscleral pathways and the surgical pathway. This surgical pathway is then linked to a porous media computational model of a fluid bleb positioned within the sub-conjunctival tissue. The computational analysis is centered on typical functioning bleb geometry found in a human eye following glaucoma surgery. A parametric study is conducted of changes in fluid absorption by the sub-conjunctival blood vessels, changes in hydraulic conductivity due to scarring, and changes in bleb size and shape, and eye outflow facility. Conclusions This study is motivated by the fact that some blebs are known to have ‘successful’ characteristics that are generally described by clinicians as being low, diffuse and large without the formation of a distinct sub-conjunctival encapsulation. The model predictions are shown to accord with clinical observations in a number of key ways, specifically the variation of intra-ocular pressure with bleb size and shape and the correspondence between sites of predicted maximum interstitial fluid pressure and key features observed in blebs, which gives validity to the model described here. This model should contribute to a more complete explanation of the physical processes behind successful bleb characteristics and provide a new basis for clinically grading blebs

Tools for Inventing Organizations: Toward a Handbook of Organizational Processes

This paper reports on the first five years of work in a project to address these problems by (1) developing methodologies and software tools for representing and codifying organizational processes at varying levels of abstraction, and (2) collecting, organizing, and analyzing numerous examples of how different groups and companies perform similar functions. The result of this work is an on-line process handbook which can be used to help people: (1) redesign existing business processes, (2) invent new processes (especially those that take advantage of information technology), and (3) organize and share knowledge about organizational practices. We also expect this process handbook to be useful in automatically (or semiautomatically) generating software to support or analyze business processes, but that is not the focus of this paper (see Dellarocas 1996, 1997a, 1997b)

Attitudes and norms affecting scientists’ data reuse

The value of sharing scientific research data is widely appreciated, but factors that hinder or prompt the reuse of data remain poorly understood. Using the Theory of Reasoned Action, we test the relationship between the beliefs and attitudes of scientists towards data reuse, and their self-reported data reuse behaviour. To do so, we used existing responses to selected questions from a worldwide survey of scientists developed and administered by the DataONE Usability and Assessment Working Group (thus practicing data reuse ourselves). Results show that the perceived efficacy and efficiency of data reuse are strong predictors of reuse behaviour, and that the perceived importance of data reuse corresponds to greater reuse. Expressed lack of trust in existing data and perceived norms against data reuse were not found to be major impediments for reuse contrary to our expectations. We found that reported use of models and remotely-sensed data was associated with greater reuse. The results suggest that data reuse would be encouraged and normalized by demonstration of its value. We offer some theoretical and practical suggestions that could help to legitimize investment and policies in favor of data sharing

What factors do scientists perceive as promoting or hindering scientific data reuse?

Increased calls for data sharing have formed part of many governments' agendas to boost innovation and scientific development. Data openness for reuse also resonates with the recognised need for more transparent, reproducible science. But what are scientists' perceptions about data reuse? Renata Gonçalves Curty, Kevin Crowston, Alison Specht, Bruce W. Grant and Elizabeth D. Dalton make use of existing survey data to analyse the attitudes and norms affecting scientists’ data reuse. Perceived efficiency, efficacy, and trustworthiness are key; as is whether scientists believe data reuse is beneficial for scientific development, or perceive certain pressures contrary to the reuse of data. Looking ahead, synthesis centres can be important for supporting data-driven interdisciplinary collaborations, and leveraging new scientific discoveries based on pre-existing data

Multimodal probes : superresolution and transmission electron microscopy imaging of mitochondria, and oxygen mapping of cells, using small-molecule Ir(III) luminescent complexes

We describe an Ir(III)-based small-molecule, multimodal probe for use in both light and electron microscopy. The direct correlation of data between light- and electron-microscopy-based imaging to investigate cellular processes at the ultrastructure level is a current challenge, requiring both dyes that must be brightly emissive for luminescence imaging and scatter electrons to give contrast for electron microscopy, at a single working concentration suitable for both methods. Here we describe the use of Ir(III) complexes as probes that provide excellent image contrast and quality for both luminescence and electron microscopy imaging, at the same working concentration. Significant contrast enhancement of cellular mitochondria was observed in transmission electron microscopy imaging, with and without the use of typical contrast agents. The specificity for cellular mitochondria was also confirmed with MitoTracker using confocal and 3D-structured illumination microscopy. These phosphorescent dyes are part of a very exclusive group of transition-metal complexes that enable imaging beyond the diffraction limit. Triplet excited-state phosphorescence was also utilized to probe the O2 concentration at the mitochondria in vitro, using lifetime mapping techniques

Classifying the unknown: discovering novel gravitational-wave detector glitches using similarity learning

The observation of gravitational waves from compact binary coalescences by LIGO and Virgo has begun a new era in astronomy. A critical challenge in making detections is determining whether loud transient features in the data are caused by gravitational waves or by instrumental or environmental sources. The citizen-science project \emph{Gravity Spy} has been demonstrated as an efficient infrastructure for classifying known types of noise transients (glitches) through a combination of data analysis performed by both citizen volunteers and machine learning. We present the next iteration of this project, using similarity indices to empower citizen scientists to create large data sets of unknown transients, which can then be used to facilitate supervised machine-learning characterization. This new evolution aims to alleviate a persistent challenge that plagues both citizen-science and instrumental detector work: the ability to build large samples of relatively rare events. Using two families of transient noise that appeared unexpectedly during LIGO's second observing run (O2), we demonstrate the impact that the similarity indices could have had on finding these new glitch types in the Gravity Spy program

The Secret to Successful User Communities: An Analysis of Computer Associates’ User Groups

This paper provides the first large scale study that examines the impact of both individual- and group-specific factors on the benefits users obtain from their user communities. By empirically analysing 924 survey responses from individuals in 161 Computer Associates' user groups, this paper aims to identify the determinants of successful user communities. To measure success, the amount of time individual members save through having access to their user networks is used. As firms can significantly profit from successful user communities, this study proposes four key implications of the empirical results for the management of user communities

Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction.

Nicotinamide adenine dinucleotide (NAD) is a REDOX cofactor and metabolite essential for neuronal survival. Glaucoma is a common neurodegenerative disease in which neuronal levels of NAD decline. We assess the effects of nicotinamide (a precursor to NAD) on retinal ganglion cells (the affected neuron in glaucoma) in normal physiological conditions and across a range of glaucoma relevant insults including mitochondrial stress and axon degenerative insults. We demonstrate retinal ganglion cell somal, axonal, and dendritic neuroprotection by nicotinamide in rodent models which represent isolated ocular hypertensive, axon degenerative, and mitochondrial degenerative insults. We performed metabolomics enriched for small molecular weight metabolites for the retina, optic nerve, and superior colliculus which demonstrates that ocular hypertension induces widespread metabolic disruption, including consistent changes to α-ketoglutaric acid, creatine/creatinine, homocysteine, and glycerophosphocholine. This metabolic disruption is prevented by nicotinamide. Nicotinamide provides further neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility whilst simultaneously dampening action potential firing frequency. These data support continued determination of the utility of long-term nicotinamide treatment as a neuroprotective therapy for human glaucoma

Time evolution and asymmetry of a laser produced blast wave

Studies of a blast wave produced from carbon rods and plastic spheres in an argon background gas have been conducted using the Vulcan laser at the Rutherford Appleton Laboratory. A laser of 1500 J was focused onto these targets, and rear-side observations of an emission front were recorded using a fast-framing camera. The emission front is asymmetrical in shape and tends to a more symmetrical shape as it progresses due to the production of a second shock wave later in time, which pushes out the front of the blast wave. Plastic spheres produce faster blast waves, and the breakthrough of the second shock is visible before the shock stalls. The results are presented to demonstrate this trend, and similar evolution dynamics of experimental and simulation data from the FLASH radiation-hydrodynamics code are observed