Publications by authors named "Marr D"

Background: Rates of attainment of high-quality diabetes care have been shown to be lower for those living in more disadvantaged and rural areas. Diabetes management relies on access to care and is impacted by physical, social, and economic factors. Area deprivation index (ADI) is one way to quantify geographic disparities in aggregate.

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Rapid restoration of blood flow is critical in treating acute ischemic stroke. Current fibrinolytic therapies using tissue plasminogen activator (tPA) are limited by low recanalization rates and risks of off-target bleeding. Here, we present a strategy using tPA immobilized on micrometer-scale beads to enhance local plasmin generation.

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For targeted transport in the body, biomedical microbots (μbots) must move effectively in three-dimensional (3D) microenvironments. Swimming μbots translate via asymmetric or screw-like motions while rolling ones use friction with available surfaces to generate propulsive forces. We have previously shown that planar rotating magnetic fields assemble μm-scale superparamagnetic beads into circular μbots that roll along surfaces.

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Tissue plasminogen activator (tPA) is the only FDA-approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ~25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis.

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For in vivo applications, microbots (μbots) must move, which is a need that has led to designs, such as helical swimmers, that translate through the bulk fluid. We have previously demonstrated that, upon application of a rotating magnetic field, colloidal particles in aqueous systems can be reversibly assembled from superparamagnetic particles into μbots that translate along surfaces using wet friction. Here, we show that high-molecular-weight polymers of a size that approaches the length scale of the gap between the μbot and surface can be excluded, impacting μbot transport.

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Tissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ~25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis.

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Microbot propulsion requires unique strategies due to the dominance of viscosity and the reversible nature of microscale flows. To address this, swimmers of specific structure that translate in bulk fluid are commonly used; however, another approach is to take advantage of the inherent asymmetry of liquid/solid surfaces for microbots (μbots) to walk or roll. Using this technique, we have previously demonstrated that superparamagnetic colloidal particles can be assembled into small μbots, which can quickly roll along solid surfaces.

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Microbot (μbot)-based targeted drug delivery has attracted increasing attention due to its potential for avoiding side effects associated with systemic delivery. To date, most μbots are rigid. When rolling on surfaces, they exhibit substantial slip due to the liquid lubrication layer.

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Inflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression, and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability.

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Direct oral anticoagulants (DOACs) have become widely used for the prevention of stroke in nonvalvular atrial fibrillation (AF) and for the treatment of venous thromboembolism (VTE). Warfarin, the standard of care prior to DOACs, requires monitoring and dose adjustment to ensure patients remain appropriately anticoagulated. DOACs do not require monitoring but are significantly more expensive.

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For disease of the lung, the physical key to effective inhalation-based therapy is size; too large (10's of μm) and the particles or droplets do not remain suspended in air to reach deep within the lungs, too small (subμm) and they are simply exhaled without deposition. μBots within this ideal low-μm size range however are challenging to fabricate and would lead to devices that lack the speed and power necessary for performing work throughout the pulmonary network. To uncouple size from structure and function, here we demonstrate an approach where individual building blocks are aerosolized and subsequently assembled in situ into μbots capable of translation, drug delivery, and mechanical work deep within lung mimics.

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Magnetic colloidal chains are a microrobotic system with promising applications due to their versatility, biocompatibility, and ease of manipulation under magnetic fields. Their synthesis involves kinetic pathways that control chain quality, length, and flexibility, a process performed by first aligning superparamagnetic particles under a one-dimensional magnetic field and then chemically linking them using a four-armed maleimide-functionalized poly(ethylene glycol). Here, we systematically vary the concentration of the poly(ethylene glycol) linkers, the reaction temperature, and the magnetic field strength to study their impact on the physical properties of synthesized chains, including the chain length distribution, reaction temperature, and bending modulus.

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Microscale bots intended for targeted drug delivery must move through three-dimensional (3D) environments that include bifurcations, inclined surfaces, and curvature. In previous studies, we have shown that magnetically actuated colloidal microwheels (µwheels) reversibly assembled from superparamagnetic beads can translate rapidly and be readily directed. Here we show that, at high concentrations, µwheels assemble into swarms that, depending on applied magnetic field actuation patterns, can be designed to transport cargo, climb steep inclines, spread over large areas, or provide mechanical action.

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Background: To reestablish blood flow in vessels occluded by clots, tissue plasminogen activator (tPA) can be used; however, its efficacy is limited by transport to and into a clot and by the depletion of its substrate, plasminogen.

Objectives: To overcome these rate limitations, a platform was designed to co-deliver tPA and plasminogen based on microwheels (µwheels), wheel-like assemblies of superparamagnetic colloidal beads that roll along surfaces at high speeds.

Methods: The biochemical speed limit was determined by measuring fibrinolysis of plasma clots at varying concentrations of tPA (10-800 nM) and plasminogen (1-6 µM).

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Superparamagnetic colloidal particles can be reversibly assembled into wheel-like structures called microwheels (μwheels), which roll on surfaces due to friction and can be driven at user-controlled speeds and directions using rotating magnetic fields. Here, we describe the hardware and software to create and control the magnetic fields that assemble and direct μwheel motion and the optics to visualize them. Motivated by portability, adaptability, and low-cost, an extruded aluminum heat-dissipating frame incorporating open optics and audio speaker coils outfitted with high magnetic permeability cores was constructed.

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To overcome the reversible nature of low-Reynolds-number flow, a variety of biomimetic microrobotic propulsion schemes and devices capable of rapid transport have been developed. However, these approaches have been typically optimized for a specific function or environment and do not have the flexibility that many real organisms exhibit to thrive in complex microenvironments. Here, inspired by adaptable microbes and using a combination of experiment and simulation, we demonstrate that one-dimensional colloidal chains can fold into geometrically complex morphologies, including helices, plectonemes, lassos, and coils, and translate via multiple mechanisms that can be varied with applied magnetic field.

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Microbot locomotion is challenging because of the reversible nature of microscale fluid flow, a limitation that can be overcome by breaking flowfield symmetry with a nearby surface. We have used this strategy with rotating wheel-shaped microbots, μwheels, that roll on surfaces leading to enhanced propulsion and fast translation speeds. Despite this, studies to date on flat surfaces show that μwheels roll inefficiently with significant slip.

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Fibrinolytic agents including plasmin and plasminogen activators improve outcomes in acute ischemic stroke and thrombosis by recanalizing occluded vessels. In the decades since their introduction into clinical practice, several limitations of have been identified in terms of both efficacy and bleeding risk associated with these agents. Engineered nanoparticles and microparticles address some of these limitations by improving circulation time, reducing inhibition and degradation in circulation, accelerating recanalization, improving targeting to thrombotic occlusions, and reducing off-target effects; however, many particle-based approaches have only been used in preclinical studies to date.

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Microscale devices must overcome fluid reversibility to propel themselves in environments where viscous forces dominate. One approach, used by colloidal microwheels (μwheels) consisting of superparamagnetic particles assembled and powered by rotating ac magnetic fields, is to employ a nearby surface to provide friction. Here, we used total internal reflection microscopy to show that individual 8.

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Thrombi that occlude blood vessels can be resolved with fibrinolytic agents that degrade fibrin, the polymer that forms between and around platelets to provide mechanical stability. Fibrinolysis rates however are often constrained by transport-limited delivery to and penetration of fibrinolytics into the thrombus. Here, these limitations are overcome with colloidal microwheel (µwheel) assemblies functionalized with the fibrinolytic tissue-type plasminogen activator (tPA) that assemble, rotate, translate, and eventually disassemble via applied magnetic fields.

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Microbot propulsion has seen increasing interest in recent years as artificial methods that overcome the well-established reversible and challenging nature of microscale fluid mechanics. While controlled movement is an important feature of microbot action, many envisioned applications also involve cargo transport where microbots must be able to load and unload contents on command while tolerating complex solution chemistry. Here we introduce a physical method that uses flexible and linked superparamagnetic colloidal chains, which can form closed rings or "lassos" in the presence of a planar rotating magnetic field.

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The purpose of the current literature review was to identify, collect, review, and organize all available information concerning clandestine laboratories used to produce methamphetamine through an analysis of routinely collected data sources. There were numerous peer reviewed journals, electronic databases, websites, and commercial vendors relevant to the remediation process of methamphetamine laboratories. Our intention in this review was to produce background information as well as a reference guide relating to the critical problem of methamphetamine production nationally and internationally in addition to generating future research projects associated with the topic.

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Evidence-based practice (EBP) is a widely endorsed concept, but many occupational therapy practitioners would like to be more informed and supported in its full implementation. They need information on the evolving definitions and concepts of EBP, encouragement to develop and adopt EBP models that link to occupational therapy's professional values, and methods that translate evidence into answers for clinical questions. This column discusses these needs and makes recommendations to the American Occupational Therapy Association for addressing them.

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Background: Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators.

Aim: To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy.

Methods: We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011.

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