The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields ...to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.
Medical robots have demonstrated the ability to manipulate percutaneous instruments into soft tissue anatomy while working beyond the limits of human perception and dexterity. Robotic technologies ...further offer the promise of autonomy in carrying out critical tasks with minimal supervision when resources are limited. Here, we present a portable robotic device capable of introducing needles and catheters into deformable tissues such as blood vessels to draw blood or deliver fluids autonomously. Robotic cannulation is driven by predictions from a series of deep convolutional neural networks that encode spatiotemporal information from multimodal image sequences to guide real-time servoing. We demonstrate, through imaging and robotic tracking studies in volunteers, the ability of the device to segment, classify, localize and track peripheral vessels in the presence of anatomical variability and motion. We then evaluate robotic performance in phantom and animal models of difficult vascular access and show that the device can improve success rates and procedure times compared to manual cannulations by trained operators, particularly in challenging physiological conditions. These results suggest the potential for autonomous systems to outperform humans on complex visuomotor tasks, and demonstrate a step in the translation of such capabilities into clinical use.Getting safe and fast access to blood vessels is vital to many methods of treatment and diagnosis in medicine. Robot-assisted or even fully autonomous methods can potentially do the task more reliably than humans, especially when veins are hard to detect. In this work, a method is tested that uses deep learning to find blood vessels and track the movement of a patient’s arm.
Robotic systems have slowly entered the realm of modern medicine; however, outside the operating room, medical robotics has yet to be translated to more routine interventions such as blood sampling ...or intravenous fluid delivery. In this paper, we present a medical robot that safely and rapidly cannulates peripheral blood vessels-a procedure commonly known as venipuncture. The device uses near-infrared and ultrasound imaging to scan and select suitable injection sites, and a 9-DOF robot to insert the needle into the center of the vessel based on image and force guidance. We first present the system design and visual-servoing scheme of the latest generation robot, and then evaluate the performance of the device through workspace simulations and free-space positioning tests. Finally, we perform a series of motion tracking experiments using stereo vision, ultrasound, and force sensing to guide the position and orientation of the needle tip. Positioning experiments indicate sub-millimeter accuracy and repeatability over the operating workspace of the system, while tracking studies demonstrate real-time needle servoing in response to moving targets. Finally, robotic phantom cannulations demonstrate the use of multiple system states to confirm that the needle has reached the center of the vessel.
Each layer receives input from previous layers (the first of which represents the input data), and then transmits a transformed version of its own weighted output that serves as input into subsequent ...layers of the network. ...the process of “training” a neural network is the tuning of the layers’ weights to minimize a cost or loss function that serves as a surrogate of the prediction error. In many circumstances, deep learning can learn more complex relationships and make more accurate predictions than other methods. ...deep learning has become its own subfield of machine learning. While large amounts of high-quality data may be available in the areas of biology where data collection is thoroughly automated, such as DNA sequencing, areas of biology that rely on manual data collection may not possess enough data to train and apply deep learning models effectively. ...to the large-scale computational demands of deep learning, traditional machine learning models can often be trained on laptops (or even on a $5 computer 31) in seconds to minutes. ...due to this enormous disparity in resource demand alone, traditional machine learning approaches may be desirable in various biological applications.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In large rivers, the ratios of silicon (Si)/nitrogen (N)/phosphorus (P) have changed dramatically as anthropogenic additions of N or P are not matched by Si. Wastewater effluent is a recognized ...source of N and P to coastal environments. Few previous studies, however, have examined the Si load of a large wastewater plant’s effluent or the molar ratios of Si/N and Si/P in effluent. We examine the annual flux of dissolved silicon (DSi) carried by effluent from the second largest treatment plant by flow in the United States (Deer Island Treatment Plant, DITP, Boston, MA). We compare treatment plant nutrient fluxes to local urban river nutrient fluxes and trace the impact of the DITP DSi loading on receiving waters. Estimates (±95% confidence interval) of treated effluent (67 800 ± 1500 kmol DSi year–1) compared to untreated (69 500 kmol DSi year–1) indicate that the process of sewage treatment at DITP likely does not remove DSi. DITP effluent was Si-limited and this Si-limitation is reflected in the receiving waters (Massachusetts Bay). However, Si-limitation appears only in the area immediately surrounding the effluent discharge. We use these results to explain phytoplankton patterns in Massachusetts Bay and to provide the first estimate of DSi loading (3.6 Gmol SiO2 year–1) from wastewater effluent across the US.
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IJS, KILJ, NUK, PNG, UL, UM
Purpose:
This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The ...phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions.
Methods:
The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 μm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2–6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data.
Results:
The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400–1100 nm, as well as the acoustic properties in the frequency range of 2–9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C.
Conclusions:
The phantoms described in this work simulate the mechanical, optical, and acoustic properties of human skin tissues, vessel tissue, and blood. In this way, the phantoms are uniquely suited to serve as test models for multimodal imaging techniques and image-guided interventions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
RATIONALE:Blood flow-induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive ...transcription factor TWIST is expressed during embryogenesis but its role in EC responses to shear stress and focal atherosclerosis is unknown.
OBJECTIVE:Investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis, and compare TWIST function in vascular development and disease.
METHODS AND RESULTS:The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by qPCR and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness.
CONCLUSIONS:TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus pleiotropic functions of TWIST control vascular disease as well as development.
Human impacts on silicon (Si) cycling are just being explored. In particular, we know little about the role of urban environments in altering the flux of Si from land to sea. Here we describe the ...annual load of dissolved Si (DSi) in the influent of the second largest wastewater treatment plant (by volume) in the United States (Deer Island Wastewater Facility, Boston, MA). We partition the ∼69 500 kmol DSi year–1 influent load between three sources: runoff (12%), groundwater infiltration (39%), and sewage (49%). Based on these results, we hypothesized that instead of being delivered to local rivers, DSi in groundwater and runoff is redirected to the combined stormwater-sewage overflow system. To test this hypothesis we compared long-term (2007–2012) observations of DSi flux from the three urban rivers surrounding Boston to modeled DSi fluxes based on land use and land cover. As predicted, the modeled fluxes were higher than the measured fluxes indicating that the sewage infrastructure of Boston diverts watershed DSi to the treatment plant. This research increases our understanding of human changes to the Si cycle, demonstrates the potential usefulness of DSi as a groundwater infiltration tracer within sewage treatment systems, and highlights the underappreciated interannual variability of riverine DSi fluxes.
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IJS, KILJ, NUK, PNG, UL, UM
Human influences on global silicon (Si) cycling include land-use change, deforestation, and wastewater discharge. Here we quantified the effect of urban expansion and historic land fill on dissolved ...silica (DSi) concentrations in urban groundwater in a northern temperate city. We hypothesized that historical land use, fill material, and urban infrastructure buried below cities create a unique anthropogenic geology which acts as a DSi source. We found that concentrations of DSi in urban groundwater are significantly higher than those from non-urban environments. We also found that historic land-use variables out-perform traditional topographic variables predicting urban DSi concentrations. We show that higher groundwater DSi concentrations result in increased subterranean groundwater discharge (SGD) fluxes, thereby altering coastal receiving water DSi availability. Further, we demonstrate that accounting for urban SGD DSi fluxes globally, could increase DSi SGD export by 20%. Together these results call for a re-evaluation of anthropogenic impacts on the global Si cycle.
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•Historic land reclamation increases urban groundwater Si concentrations.•Urban expansion elevates groundwater Si export from a northern temperate city.•Human activities have direct and long-lived impacts on the global Si cycle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Greenhouse production of vegetables is a growing global trade. While greenhouses are typically captured under regulations aimed at farmland, they may also function as a point source of effluent. In ...this study, the cumulative impacts greenhouse effluents have on riverine macronutrient and trace metal concentrations were examined. Water samples were collected Bi-weekly for five years from 14 rivers in agriculturally dominated watersheds in southwestern Ontario. Nine of the watersheds contained greenhouses with their boundaries. Greenhouse influenced rivers had significantly higher concentrations of macronutrients (nitrogen, phosphorus, and potassium) and trace metals (copper, molybdenum, and zinc). Concentrations within greenhouse influenced rivers appeared to decrease over the 5-year study while concentrations within non-greenhouse influenced river remained constant. The different temporal pattern between river types was attributed to increased precipitation during the study period. Increases in precipitation diluted concentrations in greenhouse influenced rivers; however, non-influenced river runoff proportionally increased nutrient mobility and flow, stabilizing the observed concentrations of non-point sources. Understanding the dynamic nature of environmental releases of point and non-point sources of nutrients and trace metals in mixed agricultural systems using riverine water chemistry is complicated by changes in climatic conditions, highlighting the need for long-term monitoring of nutrients, river flows and weather data in assessing these agricultural sectors.
Influence of agriculture type within watershed on stream chemistry. Display omitted
•Greenhouse production of vegetables is a globally important industry.•Nutrients and trace metals quantified in greenhouse and non-greenhouse rivers.•Greenhouse river concentrations were 4× to 28× higher than non-greenhouse rivers.•Concentrations in greenhouse rivers appeared to decrease over time.•Increased precipitation likely diluted greenhouse influenced river concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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